A Phase 1/2 interventional study of Avelumab Phase 1b and Talazoparib Phase 1b in Avelumab in Combination With Talazoparib Will be Investigated in Patients With Locally Advanced (Primary or Recurrent) or Metastatic Solid Tumors, sponsored by Pfizer. Terminated at 66 sites in 9 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-13.
Sponsored by Pfizer · Phase 1/2, Interventional, and Treatment
Avelumab in combination with talazoparib will be investigated in patients with locally advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration resistant prostate cancer (CRPC).
Avelumab is a human immunoglobulin (Ig)G1 monoclonal antibody (mAb) directed against programmed death ligand 1 (PD L1). Avelumab selectively binds to PD L1 and competitively blocks its interaction with programmed death receptor 1 (PD 1), thereby interfering with this key immune checkpoint inhibition pathway. Avelumab is currently being investigated as single agent and in combination with other anti cancer therapies in patients with locally advanced or metastatic solid tumors and various hematological malignancies.
Talazoparib is a potent, orally bioavailable poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor, which is cytotoxic to human cancer cell lines harboring gene mutations that compromise deoxyribonucleic acid (DNA) repair, an effect referred to as synthetic lethality, and by trapping PARP protein on DNA thereby preventing DNA repair, replication, and transcription.
Avelumab in combination with talazoparib will be investigated in patients with locally advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration resistant prostate cancer (CRPC).
Pfizer is the lead sponsor of 3,334 studies on the registry; 149 are open to participants now.
Of its 601 completed or terminated interventional studies of FDA-regulated products, 391 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 1b · Drug: Talazoparib Phase 1b
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 1b · Drug: Talazoparib Phase 1b
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 1b · Drug: Talazoparib Phase 1b
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 2 · Drug: Talazoparib Phase 2
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 2 · Drug: Talazoparib Phase 2
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 2 · Drug: Talazoparib Phase 2
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 2 · Drug: Talazoparib Phase 2
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 2 · Drug: Talazoparib Phase 2
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 2 · Drug: Talazoparib Phase 2
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 2 · Drug: Talazoparib Phase 2
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 2 · Drug: Talazoparib Phase 2
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 2 · Drug: Talazoparib Phase 2
Drug: Avelumab Drug: Talazoparib
Drug: Avelumab Phase 2 · Drug: Talazoparib Phase 2
Avelumab
Also known as: MSB0010718C
Talazoparib
Also known as: MDV3800, BMN 673
The dose will be determined after the overall available data (including safety and preliminary anti tumor activity) emerging from the Phase 1b portion of the study have been evaluated.
Also known as: MSB0010718C
The dose will be determined after the overall available data (including safety and preliminary anti tumor activity) emerging from the Phase 1b portion of the study have been evaluated.
Also known as: MDV3800, BMN 673
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs=occurrence of any of the following AEs attributable to any study treatment in Cycle 1:Hematologic: grade(G)4 neutropenia lasting \>5 days (absolute neutrophil count \[ANC\]\< 0.5\*10\^9/L); febrile neutropenia; neutropenic infection (ANC\<1.0\*10\^9/L, and G\>3 infection); G\>=3 thrombocytopenia (platelet count \[PC\] \<50.0\*10\^9/L) with bleeding; G4 thrombocytopenia (PC\<25.0\*10\^9/L); G4 anemia (life-threatening; urgent intervention indicated). Non-hematologic: G\>=3 toxicities unless predefined in the protocol; potential Hy's law cases. Non-adherence to treatment schedule: failure to deliver at least 75% of the planned doses of talazoparib during the first cycle of treatment due to treatment-related toxicities; G3 non-hematologic toxicity that delayed administration of either study drug for more than 2 weeks. Dose reductions: any adverse event (AE) that resulted in a dose reduction of talazoparib.
Time frame: Cycle 1; 28 days
Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment
This outcome measure (OM) is reported for participants with solid tumors except mCRPC; for those participants, OR was defined as a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version(v) 1.1 by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-progressive disease (PD), where PD is unequivocal progression of pre-existing lesions.
Time frame: From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately)
Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per RECIST v1.1 and Prostate Cancer Working Group 3 (PCWG3) by Investigator Assessment
This OM is reported for participants with mCRPC; for those participants, OR was defined as the proportion of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 and with no evidence of confirmed bone disease progression per PCWG3 criteria by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-PD.
Time frame: From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Adverse event (AE) was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Number of Participants With Grade >=3 TEAEs
AE was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. TEAEs were graded by the investigator using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with Grade 3 or higher TEAEs were reported.
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Number of Participants With Serious TEAEs
TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs). A serious TEAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/considered to be an important medical event: death; life-threatening experience (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect.
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Number of Participants With TEAEs Leading to Discontinuation of Either Study Drug
Either study drug = avelumab only or talazoparib only. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Number of Participants With TEAEs Leading to Discontinuation of All Study Drugs
All study drugs = all study drugs in the combination. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Number of Participants With TEAEs Leading to Death
TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first.
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=1 During the On-Treatment Period
The number of participants with newly occurring or worsening hematology abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=3 During the On-Treatment Period
The number of participants with newly occurring or worsening hematology abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=1 During the On-Treatment Period
The number of participants with newly occurring or worsening chemistry abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=3 During the On-Treatment Period
The number of participants with newly occurring or worsening chemistry abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Trough Concentrations (Ctrough)/Predose and Maximum Concentrations (Cmax) of Serum Avelumab Concentrations (μg/mL) by Visit (Excluding Site 1055)
Pharmacokinetics (PK) data analyses included descriptive summary statistics of the pre-dose/Ctrough concentrations for both investigational products and post-dose (for talazoparib) or Cmax concentrations (for avelumab) for each cycle.
Time frame: Predose/0 Hour (H) and 1 H on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2-4, and additionally on Day 1 of Cycles 6, 9, 12, 18, and 24.
Predose and Postdose Plasma Talazoparib Concentrations (pg/mL) by Visit (Excluding Site 1055)
Pharmacokinetics (PK) data analyses included descriptive summary statistics of the pre-dose/Ctrough concentrations for both investigational products and post-dose (for talazoparib) or Cmax concentrations (for avelumab) for each cycle. Cmax=maximum concentration. Ctrough=trough concentration. Participants with moderate renal impairment were started at a lower, 0.75 mg QD, dose to compensate for decreased talazoparib clearance.
Time frame: Pre-dose and post-dose (at the end of the avelumab infusion) on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2-4.
Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)
Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline was defined as the last assessment prior to the date/time of the first dose of avelumab. N0, N1, N2, and N3=Number of participants with at least 1 valid ADA result at any time point, baseline (pre-dose on Day 1), baseline and post-baseline, and post-baseline, respectively.
Time frame: Pre-dose (within 2 hours of talazoparib dose) on Day 1 and Day 15 of Cycle 1, on Day 1 of Cycle 2-4 and then on Day 1 of Cycles 6, 9, 12, 18, 24, and at the end of treatment (EOT)
Number of Participants by ADA Categories
Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline was defined as the last assessment prior to the date/time of the first dose of avelumab. N0, N1, N2, and N3=Number of participants with at least 1 valid ADA Result at any time point, baseline (pre-dose on Day 1), baseline and post-baseline, and post-baseline, respectively. n=number of participants in each category.
Time frame: Pre-dose (within 2 hours of talazoparib dose) on Day 1 and Day 15 of Cycles 1, on Day 1 of Cycle 2-4 and then on Day 1 of Cycles 6, 9, 12, 18, 24, and at the end of treatment (EOT)
Phase 1b: Percentage of Participants With Confirmed OR as Per RECIST v1.1 and PCWG3 by Investigator Assessment
This OM is reported for participants in Phase 1b; OR was defined as the proportion of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 and with no evidence of confirmed bone disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-PD.
Time frame: From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Phase 1b: Time to Response (TTR) in Participants With Confirmed CR or PR
For participants with solid tumors except mCRPC, TTR was defined for participants with confirmed OR (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC, TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a best overall response (BOR) of CR or PR as assessed by Investigator using RECIST v1.1.
Time frame: From the first dose of study treatment to the first documentation of objective tumor response/the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression (<=5.2 years approximately)
Phase 2: TTR in Participants With Confirmed CR or PR
For participants with solid tumors except mCRPC, TTR was defined for participants with confirmed OR (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC, TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a best overall response (BOR) of CR or PR as assessed by Investigator using RECIST v1.1.
Time frame: From the first dose of study treatment to the first documentation of objective tumor response/the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression (<= 5.2 years approximately)
Phase 2: Duration of Response (DR) in Participants With Confirmed CR or PR
For participants with solid tumors except mCRPC, DR was defined for participants with confirmed OR (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.
Time frame: From the first objective tumor response/soft tissue response to the first objective tumor progression/subsequent objective evidence of radiographic progression or death due to any cause, whichever occurred first (<=5.2 years approximately)
Phase 1b: Progression-Free Survival (PFS) in Participants With Confirmed CR or PR
For participants with solid tumors except mCRPC, PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For participants with mCRPC, PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue as assessed by Investigator using RECIST v1.1, in bone as assessed by Investigator using PCWG3, or death, whichever occurred first
Time frame: From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1)
This OM is reported for participants with solid tumors except mCRPC; for those participants, PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first.
Time frame: From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1 and PCWG3)
This OM was reported for participants with mCRPC; for these participants, PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue as assessed by Investigator using RECIST v1.1, in bone as assessed by Investigator using PCWG3, or death, whichever occurred first.
Time frame: From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Phase 2: Time to Prostate-Specific Antigen (PSA) Progression for Participants With mCRPC
Time to PSA progression for participants with mCRPC was defined as the time from the first dose to the date that a \>=25% increase in PSA with an absolute increase of \>=2 μg/L (2 ng/mL) above the nadir (or baseline for participants with no PSA decline) was documented, confirmed by a second consecutive PSA value obtained \>=3 weeks (21 days) later.
Time frame: From the first dose to the date that a >=25% increase in PSA with an absolute increase of >=2 μg/L (2 ng/mL) above the nadir (or baseline for participants with no PSA decline) was documented (maximum up to 5.2 years approximately)
Phase 1b: Overall Survival
Overall survival (OS) was defined as the time from the first dose of study treatment to the date of death. Participants without an event (death) were censored at the date of last contact.
Time frame: From the first dose of study treatment to the date of death (maximum up to 5.2 years approximately)
Phase 2: Overall Survival
OS was defined as the time from the first dose of study treatment to the date of death. Participants without an event (death) were censored at the date of last contact.
Time frame: From the first dose of study treatment to the date of death (maximum up to 5.2 years approximately)
Phase 2: Percentage of Participants With PSA Response
PSA response was defined as the proportion of participants with confirmed PSA decline \>=50% compared to baseline. PSA response was calculated as a decline from baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50%. A PSA response must be confirmed by a second consecutive value at least 3 weeks later.
Time frame: From baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50% (maximum up to 5.2 years approximately)
Phase 1b: Percentage of Participants With CA-125 Response
Cancer Antigen 125 (CA-125) response is defined as at least a 50% reduction in CA-125 levels from baseline. The response must be confirmed and maintained for at least 28 days.
Time frame: From baseline to at least a 50% reduction in CA-125 level (maximum up to 5.2 years approximately)
Phase 2: Percentage of Participants With CA-125 Response
CA-125 response is defined as at least a 50% reduction in CA-125 levels from baseline. The response must be confirmed and maintained for at least 28 days.
Time frame: From baseline to at least a 50% reduction in CA-125 level (maximum up to 5.2 years approximately)
Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline
PD-L1 expression on tumor and infiltrating immune cells were measured by immunohistochemistry (IHC). PD-L1 expression level corresponds to the percentage of positive cells. The PD-L1 Positive category does not apply to cohorts A1 and A2. The PD-L1 High/Low categories only apply to cohorts A1 and A2. Participants were considered positive if their baseline tumor tissue sample demonstrated cell surface PD-L1 expression: 1) for Cohorts E1, E2, and F: \>=1% tumor cells (TC) or \>= 5% immune cells (IC); 2) for Cohort D: TC/IC\>=25%; 3) for Cohorts B1, B2, C1, C2: IC\>=5%; otherwise were considered negative. Categories based on PD-L1 expression level ≥50% and \<50% were defined as High and Low, respectively.
Time frame: At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)
Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline
TMB was defined as the total number of mutations in the tumor genome, or number of mutations per megabase of DNA if derived from targeted sequencing. High: TMB score \>=20 muts/mb (number of mutations per megabase of DNA); Medium: TMB score \>=10 muts/mb and \<20 muts/mb; Low: TMB score \<10 muts/mb.
Time frame: At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)
Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline
DDR defect positive was determined by presence of one or more pathogenic or likely pathogenic mutations in tissue, DNA and/or blood samples.
Time frame: At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)
The study was conducted in 2 phases: Phase 1b (talazoparib dose level cohorts) and Phase 2 (expansion phase). The Phase 1b study design started at the highest dose of talazoparib (1 mg QD), to be de-escalated to 0.75 and 0.5 mg QD. With DLT rate \<33% among 12 DLT-evaluable patients treated at 1 mg, Phase 2 started. The 2 cohorts at lower dose did not enroll any participants and are not displayed in the results. Only the Phase 1b cohort "Avelumab 800 mg Q2W + Talazoparib 1 mg QD" is displayed.
| Milestone | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 12 | 42 | 5 | 22 | 23 | 20 | 11 | 40 | 21 | 18 | 9 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 12 | 42 | 5 | 22 | 23 | 20 | 11 | 40 | 21 | 18 | 9 |
| Withdrew: Other | 1 | 3 | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Progressive disease | 8 | 27 | 4 | 18 | 16 | 14 | 7 | 29 | 9 | 11 | 5 |
| Withdrew: Withdrawal by subject | 1 | 4 | 0 | 1 | 1 | 1 | 0 | 2 | 2 | 1 | 1 |
| Withdrew: Global deterioration of health status | 2 | 3 | 0 | 2 | 3 | 3 | 0 | 2 | 8 | 4 | 1 |
| Withdrew: Adverse event | 0 | 1 | 0 | 1 | 1 | 1 | 3 | 4 | 2 | 2 | 2 |
| Withdrew: Death | 0 | 4 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 |
| Withdrew: Physician decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
DLTs=occurrence of any of the following AEs attributable to any study treatment in Cycle 1:Hematologic: grade(G)4 neutropenia lasting \>5 days (absolute neutrophil count \[ANC\]\< 0.5\*10\^9/L); febrile neutropenia; neutropenic infection (ANC\<1.0\*10\^9/L, and G\>3 infection); G\>=3 thrombocytopenia (platelet count \[PC\] \<50.0\*10\^9/L) with bleeding; G4 thrombocytopenia (PC\<25.0\*10\^9/L); G4 anemia (life-threatening; urgent intervention indicated). Non-hematologic: G\>=3 toxicities unless predefined in the protocol; potential Hy's law cases. Non-adherence to treatment schedule: failure to deliver at least 75% of the planned doses of talazoparib during the first cycle of treatment due to treatment-related toxicities; G3 non-hematologic toxicity that delayed administration of either study drug for more than 2 weeks. Dose reductions: any adverse event (AE) that resulted in a dose reduction of talazoparib.
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD |
|---|---|
| Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) | 3 |
This outcome measure (OM) is reported for participants with solid tumors except mCRPC; for those participants, OR was defined as a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version(v) 1.1 by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-progressive disease (PD), where PD is unequivocal progression of pre-existing lesions.
| Percentage of Participants | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|---|---|---|---|---|
| Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment | 16.7 (7.0 to 31.4) | 20.0 (0.5 to 71.6) | 18.2 (5.2 to 40.3) | 34.8 (16.4 to 57.3) | 20.0 (5.7 to 43.7) | 63.6 (30.8 to 89.1) | 15.0 (5.7 to 29.8) | 0 (0.0 to 41.0) |
This OM is reported for participants with mCRPC; for those participants, OR was defined as the proportion of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 and with no evidence of confirmed bone disease progression per PCWG3 criteria by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-PD.
| Percentage of Participants | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|
| Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per RECIST v1.1 and Prostate Cancer Working Group 3 (PCWG3) by Investigator Assessment | 0 (0.0 to 16.1) | 11.1 (1.4 to 34.7) | 50.0 (1.3 to 98.7) |
Adverse event (AE) was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| Participants with all-causality TEAEs | 12 | 207 |
| Participants with treatment-related TEAEs | 11 | 197 |
AE was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. TEAEs were graded by the investigator using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with Grade 3 or higher TEAEs were reported.
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| Participants with all-causality Grade >=3 TEAEs | 9 | 156 |
| Participants with treatment-related Grade >=3 TEAEs | 9 | 120 |
TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs). A serious TEAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/considered to be an important medical event: death; life-threatening experience (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect.
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| Participants with all-causality serious TEAEs | 1 | 75 |
| Participants with treatment-related serious TEAEs | 1 | 25 |
Either study drug = avelumab only or talazoparib only. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| Participants with all-causality TEAEs leading to discontinuation of avelumab only | 0 | 5 |
| Participants with treatment-related TEAEs leading to discontinuation of avelumab only | 0 | 4 |
| Participants with all-causality TEAEs leading to discontinuation of talazoparib only | 1 | 9 |
| Participants with treatment-related TEAEs leading to discontinuation of talazoparib only | 1 | 8 |
All study drugs = all study drugs in the combination. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| Participants with all-causality TEAEs leading to discontinuation of all study drugs | 1 | 20 |
| Participants with treatment-related TEAEs leading to discontinuation of all study drugs | 0 | 1 |
TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first.
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| Participants with all-causality TEAEs leading to death | 0 | 21 |
| Participants with treatment-related TEAEs leading to death | 0 | 1 |
The number of participants with newly occurring or worsening hematology abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| Activated partial thromboplastin time prolonged | 4 | 21 |
| Anemia | 8 | 161 |
| Hemoglobin increased | 0 | 1 |
| Lymphocyte count decreased | 9 | 145 |
| Lymphocyte count increased | 1 | 3 |
| Neutrophil count decreased | 8 | 100 |
| Platelet count decreased | 6 | 141 |
| White blood cell decreased | 10 | 139 |
The number of participants with newly occurring or worsening hematology abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| Activated partial thromboplastin time prolonged | 0 | 1 |
| Anemia | 4 | 78 |
| Lymphocyte count decreased | 4 | 44 |
| Neutrophil count decreased | 5 | 27 |
| Platelet count decreased | 4 | 47 |
| White blood cell decreased | 3 | 20 |
The number of participants with newly occurring or worsening chemistry abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| Alanine aminotransferase increased | 1 | 41 |
| Alkaline phosphatase increased | 3 | 74 |
| Aspartate aminotransferase increased | 2 | 53 |
| Blood bilirubin increased | 0 | 24 |
| Creatinine Phosphokinase (CPK) increased | 2 | 37 |
| Creatinine increased | 9 | 147 |
| Gamma-glutamyl transferase (GGT) increased | 2 | 69 |
| Hypercalcemia | 1 | 23 |
| Hyperglycemia | 0 | 48 |
| Hyperkalemia | 2 | 25 |
| Hypermagnesemia | 0 | 21 |
| Hypernatremia | 0 | 9 |
| Hypoalbuminemia | 2 | 60 |
| Hypocalcemia | 1 | 45 |
| Hypoglycemia | 0 | 13 |
| Hypokalemia | 3 | 36 |
| Hypomagnesemia | 2 | 33 |
| Hyponatremia | 4 | 66 |
| Hypophosphatemia | 2 | 43 |
| Lipase increased | 4 | 36 |
| Serum amylase increased | 2 | 32 |
The number of participants with newly occurring or worsening chemistry abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| Alanine aminotransferase increased | 0 | 2 |
| Alkaline phosphatase increased | 0 | 7 |
| Aspartate aminotransferase increased | 0 | 2 |
| Blood bilirubin increased | 0 | 3 |
| Creatinine Phosphokinase (CPK) increased | 0 | 4 |
| Creatinine increased | 0 | 2 |
| Gamma-glutamyl transferase (GGT) increased | 0 | 11 |
| Hyperglycemia | 0 | 6 |
| Hyperkalemia | 0 | 1 |
| Hypermagnesemia | 0 | 5 |
| Hypoalbuminemia | 0 | 2 |
| Hypocalcemia | 0 | 4 |
| Hypokalemia | 0 | 1 |
| Hyponatremia | 0 | 12 |
| Hypophosphatemia | 1 | 6 |
| Lipase increased | 0 | 14 |
| Serum amylase increased | 0 | 7 |
Pharmacokinetics (PK) data analyses included descriptive summary statistics of the pre-dose/Ctrough concentrations for both investigational products and post-dose (for talazoparib) or Cmax concentrations (for avelumab) for each cycle.
| μg/mL | Phase 1b and Phase 2 Combined |
|---|---|
| Cycle 1 / Day 1 (0 Hour [H]) | NA ± NA |
| Cycle 1 / Day 1 (1 H) | 221.0 ± 41 |
| Cycle 1 / Day 15 (0 H) | 21.20 ± 72 |
| Cycle 1 / Day 15 (1 H) | 206.6 ± 86 |
| Cycle 2 / Day 1 (0 H) | 26.41 ± 68 |
| Cycle 2 / Day 1 (1 H) | 199.6 ± 110 |
| Cycle 3 / Day 1 (0 H) | 31.45 ± 80 |
| Cycle 3 / Day 1 (1 H) | 188.8 ± 105 |
| Cycle 4 / Day 1 (0 H) | 34.59 ± 81 |
| Cycle 4 / Day 1 (1 H) | 190.6 ± 99 |
| Cycle 6 / Day 1 (0 H) | 37.40 ± 73 |
| Cycle 6 / Day 1 (1 H) | 185.9 ± 98 |
| Cycle 9 / Day 1 (0 H) | 39.97 ± 91 |
| Cycle 9 / Day 1 (1 H) | 171.1 ± 145 |
| Cycle 12 / Day 1 (0 H) | 47.10 ± 63 |
| Cycle 12 / Day 1 (1 H) | 202.9 ± 88 |
| Cycle 18 / Day 1 (0 H) | 53.94 ± 33 |
| Cycle 18 / Day 1 (1 H) | 135.6 ± 354 |
| Cycle 24 / Day 1 (0 H) | 76.40 ± NA |
| Cycle 24 / Day 1 (1 H) | 378.0 ± NA |
Pharmacokinetics (PK) data analyses included descriptive summary statistics of the pre-dose/Ctrough concentrations for both investigational products and post-dose (for talazoparib) or Cmax concentrations (for avelumab) for each cycle. Cmax=maximum concentration. Ctrough=trough concentration. Participants with moderate renal impairment were started at a lower, 0.75 mg QD, dose to compensate for decreased talazoparib clearance.
| pg/mL | Talazoparib Starting Dose = 1 mg QD | Talazoparib Starting Dose = 0.75 mg QD |
|---|---|---|
| Cycle 1 / Day 1 (Predose) | NA ± NA | NA ± NA |
| Cycle 1 / Day 1 (Postdose) | 2295 ± 137 | 2015 ± 112 |
| Cycle 1 / Day 15 (Predose) | 4672 ± 63 | 4657 ± 47 |
| Cycle 1 / Day 15 (Postdose) | 9055 ± 88 | 8257 ± 11 |
| Cycle 2 / Day 1 (Predose) | 4385 ± 53 | 5871 ± 53 |
| Cycle 2 / Day 1 (Postdose) | 8479 ± 73 | 9834 ± 62 |
| Cycle 3 / Day 1 (Predose) | 4212 ± 46 | 3874 ± 48 |
| Cycle 3 / Day 1 (Postdose) | 6765 ± 239 | 1236 ± 8074 |
| Cycle 4 / Day 1 (Predose) | 4713 ± 38 | 3826 ± 73 |
| Cycle 4 / Day 1 (Postdose) | 6506 ± 76 | 6735 ± 70 |
Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline was defined as the last assessment prior to the date/time of the first dose of avelumab. N0, N1, N2, and N3=Number of participants with at least 1 valid ADA result at any time point, baseline (pre-dose on Day 1), baseline and post-baseline, and post-baseline, respectively.
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| N0 | 12 | 211 |
| N1 | 12 | 209 |
| N2 | 11 | 202 |
| N3 | 11 | 200 |
Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline was defined as the last assessment prior to the date/time of the first dose of avelumab. N0, N1, N2, and N3=Number of participants with at least 1 valid ADA Result at any time point, baseline (pre-dose on Day 1), baseline and post-baseline, and post-baseline, respectively. n=number of participants in each category.
| Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2 |
|---|---|---|
| ADA never-positive (n/N0) | 12 | 205 |
| ADA ever-positive (n/N0) | 0 | 6 |
| ADA ever-positive: Baseline ADA positive (n/N1) (No treatment-boosted ADA [n/N2]) | 0 | 4 |
| ADA ever-positive: Treatment-induced ADA positive (n/N3) | 0 | 2 |
This OM is reported for participants in Phase 1b; OR was defined as the proportion of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 and with no evidence of confirmed bone disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-PD.
| Percentage of Particpants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD |
|---|---|
| Phase 1b: Percentage of Participants With Confirmed OR as Per RECIST v1.1 and PCWG3 by Investigator Assessment | 16.7 (2.1 to 48.4) |
For participants with solid tumors except mCRPC, TTR was defined for participants with confirmed OR (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC, TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a best overall response (BOR) of CR or PR as assessed by Investigator using RECIST v1.1.
| Months | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD |
|---|---|
| Phase 1b: Time to Response (TTR) in Participants With Confirmed CR or PR | 1.8 (1.8 to 1.8) |
For participants with solid tumors except mCRPC, TTR was defined for participants with confirmed OR (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC, TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a best overall response (BOR) of CR or PR as assessed by Investigator using RECIST v1.1.
| Months | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|---|---|---|---|---|---|
| Phase 2: TTR in Participants With Confirmed CR or PR | 3.7 (1.7 to 11.3) | 1.8 (1.8 to 1.8) | 1.8 (1.6 to 2.0) | 1.9 (1.6 to 3.6) | 3.6 (1.7 to 17.9) | 1.7 (1.6 to 3.7) | 2.1 (1.4 to 5.9) | 5.5 (5.4 to 5.6) | 1.8 (1.8 to 1.8) |
For participants with solid tumors except mCRPC, DR was defined for participants with confirmed OR (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.
| Months | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) |
|---|---|---|---|---|---|---|---|
| Phase 2: Duration of Response (DR) in Participants With Confirmed CR or PR | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
For participants with solid tumors except mCRPC, PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For participants with mCRPC, PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue as assessed by Investigator using RECIST v1.1, in bone as assessed by Investigator using PCWG3, or death, whichever occurred first
| Months | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD |
|---|---|
| Phase 1b: Progression-Free Survival (PFS) in Participants With Confirmed CR or PR | 6.0 (1.8 to 11.5) |
This OM is reported for participants with solid tumors except mCRPC; for those participants, PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first.
| Months | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|---|---|---|---|---|
| Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1) | 4.7 (3.7 to 7.4) | 1.9 (1.8 to NA) | 3.6 (1.9 to 5.6) | 5.3 (2.0 to 12.8) | 7.2 (4.0 to 9.1) | 16.8 (7.2 to NA) | 3.6 (1.9 to 5.4) | 1.7 (1.4 to 3.3) |
This OM was reported for participants with mCRPC; for these participants, PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue as assessed by Investigator using RECIST v1.1, in bone as assessed by Investigator using PCWG3, or death, whichever occurred first.
| Months | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|
| Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1 and PCWG3) | 4.1 (1.9 to NA) | 4.6 (1.7 to 9.8) | 8.4 (5.9 to 10.9) |
Time to PSA progression for participants with mCRPC was defined as the time from the first dose to the date that a \>=25% increase in PSA with an absolute increase of \>=2 μg/L (2 ng/mL) above the nadir (or baseline for participants with no PSA decline) was documented, confirmed by a second consecutive PSA value obtained \>=3 weeks (21 days) later.
| Months | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|
| Phase 2: Time to Prostate-Specific Antigen (PSA) Progression for Participants With mCRPC | 1.0 (1.0 to 4.6) | 2.8 (1.0 to 6.5) | 3.1 (1.6 to 4.6) |
Overall survival (OS) was defined as the time from the first dose of study treatment to the date of death. Participants without an event (death) were censored at the date of last contact.
| Months | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD |
|---|---|
| Phase 1b: Overall Survival | 18.5 (6.4 to NA) |
OS was defined as the time from the first dose of study treatment to the date of death. Participants without an event (death) were censored at the date of last contact.
| Months | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|---|---|---|---|---|---|---|
| Phase 2: Overall Survival | 11.6 (8.4 to 14.9) | 26.3 (3.5 to 43.3) | 8.2 (5.8 to 13.0) | 27.5 (12.6 to 40.2) | 22.9 (7.8 to NA) | 38.8 (16.9 to NA) | 13.1 (8.5 to 19.2) | 15.9 (9.6 to 20.7) | 16.1 (10.8 to 23.4) | 6.9 (1.4 to 27.4) |
PSA response was defined as the proportion of participants with confirmed PSA decline \>=50% compared to baseline. PSA response was calculated as a decline from baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50%. A PSA response must be confirmed by a second consecutive value at least 3 weeks later.
| Percentage of Participants | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) |
|---|---|---|
| Phase 2: Percentage of Participants With PSA Response | 9.5 (1.2 to 30.4) | 5.6 (0.1 to 27.3) |
Cancer Antigen 125 (CA-125) response is defined as at least a 50% reduction in CA-125 levels from baseline. The response must be confirmed and maintained for at least 28 days.
| Percentage of Participants | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD |
|---|---|
| Phase 1b: Percentage of Participants With CA-125 Response | 100 (2.5 to 100.0) |
CA-125 response is defined as at least a 50% reduction in CA-125 levels from baseline. The response must be confirmed and maintained for at least 28 days.
| Percentage of Participants | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) |
|---|---|---|
| Phase 2: Percentage of Participants With CA-125 Response | 45.0 (23.1 to 68.5) | 63.6 (30.8 to 89.1) |
PD-L1 expression on tumor and infiltrating immune cells were measured by immunohistochemistry (IHC). PD-L1 expression level corresponds to the percentage of positive cells. The PD-L1 Positive category does not apply to cohorts A1 and A2. The PD-L1 High/Low categories only apply to cohorts A1 and A2. Participants were considered positive if their baseline tumor tissue sample demonstrated cell surface PD-L1 expression: 1) for Cohorts E1, E2, and F: \>=1% tumor cells (TC) or \>= 5% immune cells (IC); 2) for Cohort D: TC/IC\>=25%; 3) for Cohorts B1, B2, C1, C2: IC\>=5%; otherwise were considered negative. Categories based on PD-L1 expression level ≥50% and \<50% were defined as High and Low, respectively.
| Participants | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|---|---|---|---|---|---|---|
| High | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Low | 8 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Positive (Not applicable for Cohorts A1 and A2) | 0 | 0 | 8 | 3 | 5 | 5 | 13 | 1 | 2 | 0 |
| Negative | 22 | 2 | 6 | 16 | 13 | 4 | 19 | 13 | 12 | 3 |
| Unknown | 9 | 1 | 8 | 4 | 2 | 2 | 8 | 7 | 4 | 6 |
TMB was defined as the total number of mutations in the tumor genome, or number of mutations per megabase of DNA if derived from targeted sequencing. High: TMB score \>=20 muts/mb (number of mutations per megabase of DNA); Medium: TMB score \>=10 muts/mb and \<20 muts/mb; Low: TMB score \<10 muts/mb.
| Participants | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|---|---|---|---|---|---|---|
| High | 4 | 1 | 0 | 0 | 0 | 0 | 5 | 0 | 2 | 0 |
| Medium | 9 | 1 | 3 | 2 | 1 | 2 | 4 | 0 | 0 | 0 |
| Low | 13 | 3 | 12 | 20 | 12 | 6 | 22 | 11 | 13 | 8 |
| Unknown | 16 | 0 | 7 | 1 | 7 | 3 | 9 | 10 | 3 | 1 |
DDR defect positive was determined by presence of one or more pathogenic or likely pathogenic mutations in tissue, DNA and/or blood samples.
| Participants | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|---|---|---|---|---|---|---|
| Positive | 12 | 3 | 10 | 19 | 5 | 10 | 18 | 7 | 16 | 8 |
| Negative | 30 | 2 | 12 | 4 | 15 | 1 | 22 | 13 | 2 | 1 |
| Unknown | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Collected over All-cause mortality: From start of the treatment up to 90 days post last dose of study treatment (maximum of 5.2 years approximately), TEAEs and Serious TEAEs: from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first (maximum of 5.2 years approximately).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | 6/12 (50%) | 1/12 (8.3%) | 12/12 (100%) |
| Phase 2: Cohort A1 (NSCLC) | 33/42 (78.6%) | 16/42 (38.1%) | 41/42 (97.6%) |
| Phase 2: Cohort A2 (NSCLC DDR+) | 3/5 (60%) | 2/5 (40%) | 5/5 (100%) |
| Phase 2: Cohort B1 (TNBC) | 16/22 (72.7%) | 7/22 (31.8%) | 21/22 (95.5%) |
| Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | 16/23 (69.6%) | 5/23 (21.7%) | 22/23 (95.7%) |
| Phase 2: Cohort C1 (OVC) | 11/20 (55%) | 9/20 (45%) | 20/20 (100%) |
| Phase 2: Cohort C2 (OVC BRCA-mutated) | 6/11 (54.5%) | 2/11 (18.2%) | 10/11 (90.9%) |
| Phase 2: Cohort D (UC) | 26/40 (65%) | 16/40 (40%) | 38/40 (95%) |
| Phase 2: Cohort E1 (mCRPC) | 16/21 (76.2%) | 5/21 (23.8%) | 21/21 (100%) |
| Phase 2: Cohort E2 (mCRPC DDR+) | 14/18 (77.8%) | 9/18 (50%) | 16/18 (88.9%) |
| Phase 2: Cohort F (BRCA/ATM-mutated) | 7/9 (77.8%) | 4/9 (44.4%) | 9/9 (100%) |
| Event | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| ThrombocytopeniaBlood and lymphatic system disorders | 0/12 | 0/42 | 0/5 | 1/22 | 0/23 | 0/20 | 1/11 | 0/40 | 0/21 | 0/18 | 2/9 |
| Disease progressionGeneral disorders | 0/12 | 2/42 | 0/5 | 2/22 | 1/23 | 2/20 | 0/11 | 1/40 | 0/21 | 1/18 | 2/9 |
| Testicular painReproductive system and breast disorders | 0/12 | 0/42 | 1/5 | 0/22 | 0/23 | 0/20 | 0/11 | 0/40 | 0/21 | 0/18 | 0/9 |
| HaematomaVascular disorders | 0/12 | 0/42 | 1/5 | 0/22 | 0/23 | 0/20 | 0/11 | 0/40 | 0/21 | 0/18 | 0/9 |
| AnaemiaBlood and lymphatic system disorders | 1/12 | 2/42 | 0/5 | 3/22 | 2/23 | 0/20 | 0/11 | 3/40 | 0/21 | 0/18 | 1/9 |
| ColitisGastrointestinal disorders | 0/12 | 0/42 | 0/5 | 0/22 | 0/23 | 0/20 | 0/11 | 0/40 | 0/21 | 0/18 | 1/9 |
| Infusion related reactionInjury, poisoning and procedural complications | 0/12 | 1/42 | 0/5 | 0/22 | 0/23 | 0/20 | 0/11 | 0/40 | 0/21 | 2/18 | 0/9 |
| Blood bilirubin increasedInvestigations | 0/12 | 0/42 | 0/5 | 0/22 | 0/23 | 0/20 | 0/11 | 0/40 | 0/21 | 0/18 | 1/9 |
| Neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/12 | 0/42 | 0/5 | 0/22 | 0/23 | 0/20 | 0/11 | 0/40 | 0/21 | 0/18 | 1/9 |
| Vaginal haemorrhageReproductive system and breast disorders | 0/12 | 0/42 | 0/5 | 0/22 | 0/23 | 0/20 | 0/11 | 0/40 | 0/21 | 0/18 | 1/9 |
| Event | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Neutrophil count decreasedInvestigations | 2/12 | 2/42 | 0/5 | 1/22 | 3/23 | 5/20 | 10/11 | 5/40 | 3/21 | 2/18 | 1/9 |
| AnaemiaBlood and lymphatic system disorders | 8/12 | 28/42 | 4/5 | 18/22 | 10/23 | 12/20 | 7/11 | 31/40 | 15/21 | 10/18 | 5/9 |
| FatigueGeneral disorders | 2/12 | 17/42 | 4/5 | 8/22 | 10/23 | 11/20 | 8/11 | 14/40 | 10/21 | 5/18 | 6/9 |
| NauseaGastrointestinal disorders | 0/12 | 14/42 | 0/5 | 10/22 | 11/23 | 14/20 | 6/11 | 12/40 | 8/21 | 6/18 | 2/9 |
| Platelet count decreasedInvestigations | 1/12 | 3/42 | 1/5 | 4/22 | 4/23 | 5/20 | 7/11 | 7/40 | 8/21 | 7/18 | 2/9 |
| ConstipationGastrointestinal disorders | 1/12 | 6/42 | 3/5 | 5/22 | 4/23 | 3/20 | 4/11 | 7/40 | 5/21 | 2/18 | 2/9 |
| NeutropeniaBlood and lymphatic system disorders | 7/12 | 10/42 | 2/5 | 6/22 | 4/23 | 4/20 | 2/11 | 6/40 | 3/21 | 0/18 | 2/9 |
| DysgeusiaNervous system disorders | 0/12 | 2/42 | 0/5 | 3/22 | 2/23 | 0/20 | 5/11 | 2/40 | 0/21 | 0/18 | 0/9 |
| ThrombocytopeniaBlood and lymphatic system disorders | 5/12 | 15/42 | 1/5 | 9/22 | 2/23 | 9/20 | 4/11 | 16/40 | 6/21 | 3/18 | 2/9 |
| Oedema peripheralGeneral disorders | 0/12 | 2/42 | 0/5 | 1/22 | 0/23 | 2/20 | 2/11 | 3/40 | 3/21 | 2/18 | 4/9 |
| Age, Continuous(Years) | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 62.67 ± 9.49 | 67.00 ± 9.37 | 59.60 ± 7.40 | 56.18 ± 12.49 | 53.83 ± 14.08 | 62.65 ± 10.66 | 61.36 ± 9.24 | 65.73 ± 9.19 | 63.71 ± 7.40 | 71.56 ± 7.37 | 63.00 ± 10.91 | 63.17 ± 11.04 |
| Age, Customized(Participants) | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| <65 years | 6 | 15 | 4 | 15 | 17 | 12 | 7 | 16 | 8 | 3 | 5 | 108 |
| 65 - <75 years | 5 | 19 | 1 | 6 | 3 | 5 | 3 | 16 | 12 | 8 | 2 | 80 |
| 75 - <85 years | 1 | 7 | 0 | 1 | 3 | 3 | 1 | 7 | 1 | 6 | 2 | 32 |
| >= 85 years | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 3 |
| Sex: Female, Male(Participants) | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 3 | 9 | 2 | 22 | 22 | 20 | 11 | 14 | 0 | 0 | 3 | 106 |
| Male | 9 | 33 | 3 | 0 | 1 | 0 | 0 | 26 | 21 | 18 | 6 | 117 |
| Ethnicity (NIH/OMB)(Participants) | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 3 | 1 | 0 | 7 |
| Not Hispanic or Latino | 12 | 39 | 5 | 19 | 21 | 18 | 11 | 38 | 11 | 16 | 8 | 198 |
| Unknown or Not Reported | 0 | 3 | 0 | 3 | 1 | 2 | 0 | 0 | 7 | 1 | 1 | 18 |
| Race/Ethnicity, Customized(Participants) | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Black or African American | 3 | 1 | 0 | 0 | 0 | 0 | 2 | 1 | 5 | 2 | 0 | 14 |
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Asian | 0 | 5 | 0 | 1 | 1 | 0 | 3 | 2 | 1 | 2 | 0 | 15 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| White | 9 | 34 | 4 | 20 | 17 | 18 | 6 | 36 | 12 | 14 | 9 | 179 |
| Not reported | 0 | 2 | 0 | 1 | 4 | 2 | 0 | 1 | 3 | 0 | 0 | 13 |
| Geographic Region(Participants) | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| North America | 12 | 9 | 3 | 14 | 15 | 10 | 7 | 15 | 20 | 11 | 8 | 124 |
| Western Europe | 0 | 10 | 2 | 0 | 1 | 2 | 1 | 5 | 1 | 4 | 1 | 27 |
| Eastern Europe | 0 | 19 | 0 | 6 | 4 | 5 | 1 | 16 | 0 | 1 | 0 | 52 |
| Australasia | 0 | 0 | 0 | 2 | 2 | 3 | 0 | 2 | 0 | 1 | 0 | 10 |
| Asia | 0 | 4 | 0 | 0 | 1 | 0 | 2 | 2 | 0 | 1 | 0 | 10 |
| ECOG Performance Status(Participants) | Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD | Phase 2: Cohort A1 (NSCLC) | Phase 2: Cohort A2 (NSCLC DDR+) | Phase 2: Cohort B1 (TNBC) | Phase 2: Cohort B2 (BC HR+ HER2- DDR+) | Phase 2: Cohort C1 (OVC) | Phase 2: Cohort C2 (OVC BRCA-mutated) | Phase 2: Cohort D (UC) | Phase 2: Cohort E1 (mCRPC) | Phase 2: Cohort E2 (mCRPC DDR+) | Phase 2: Cohort F (BRCA/ATM-mutated) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 4 | 5 | 1 | 12 | 12 | 9 | 8 | 16 | 4 | 6 | 1 | 78 |
| 1 | 8 | 37 | 4 | 10 | 11 | 11 | 3 | 24 | 17 | 12 | 8 | 145 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Data sharing details ↗ · www.pfizer.com
Ran from Oct 2017 to primary completion in Feb 2022, 52 months.
Results were first posted in Jun 2023, 1 year 3 months after primary completion.
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Studies of the drug tested here: Avelumab