A Phase 1/2 interventional study of Avelumab 800 mg in combination with pemetrexed / carboplatin and Avelumab 800 mg in combination with gemcitabine / cisplatin. in Non-small Cell Lung Cancer and Urothelial Cancer, sponsored by Pfizer. Terminated at 46 sites in 8 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-08-29.
Sponsored by Pfizer · Phase 1/2, Interventional, and Treatment
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Among 15 studies testing avelumab in Carcinoma, Non-Small-Cell Lung — 1 open to participants now, 2 under way, 1 of them phase 3. avelumab · Carcinoma, Non-Small-Cell Lung.
Among the 15 studies testing avelumab in Carcinoma, Non-Small-Cell Lung, this one is the 8th largest by enrollment, is one of 5 that started in 2017, is one of 5 in phase 1/2, and was the 7th registered.
7,624 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,837 are open to participants now.
Browse Carcinoma, Non-Small-Cell Lung studies →1 of the 15 studies testing avelumab in Carcinoma, Non-Small-Cell Lung is open now, in 1 country. Recruiting first, the newest first:
Institut Bergonié · Sites in France
Ages 18+
By country, each count listing its studies:
avelumab: first FDA approval 2017 (BAVENCIO), first EMA approval 2017. What it is approved for, and how studies give it, is on its page →
Of the 1,326 Carcinoma, Non-Small-Cell Lung studies recruiting now, 988 (75%) set no upper age limit and 225 (17%) stop at 75 or younger; 34 take children under 18; 40 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
15 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 9 · Phase 2 8 · Phase 3 3
First in 2013; this study’s year is marked. 5 started in 2017.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 67 is close to the median of 62 across 6,023 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Median enrollment 67 across the 15 interventional studies. Of the 12 that completed or were terminated, 10 (83%) have results posted.
This tab as a report to print or save as PDF → With an account.
9 of 15 have an industry lead sponsor. The 9 most frequent:
Pfizer is the lead sponsor of 3,337 studies on the registry; 150 are open to participants now.
Of its 601 completed or terminated interventional studies of FDA-regulated products, 392 (65%) have results posted.
158 studies in Carcinoma, Non-Small-Cell Lung by Pfizer: 15 open now, 26 under way, 5 of them phase 3. Of 123 finished, 70 (57%) have results posted.
Among the 158 studies in Carcinoma, Non-Small-Cell Lung by Pfizer, this one is the 73rd largest by enrollment of the 136 interventional ones that give a count, is one of 8 that started in 2017, is one of 13 in phase 1/2, and was the 80th registered.
Pfizer’s Carcinoma, Non-Small-Cell Lung studies by the year they started, since 1999.
1 of the studies testing avelumab in Carcinoma, Non-Small-Cell Lung that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT03815643Phase 3EMD Serono Research & Development Institute, Inc.Avelumab Program Rollover Study | 2026-11-24 |
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Among the 15 studies testing avelumab in Carcinoma, Non-Small-Cell Lung, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among Pfizer’s 158 in Carcinoma, Non-Small-Cell Lung:
This tab as a report to print or save as PDF → With an account.
This is a Phase 1b/2, open label, multicenter, safety and clinical activity study of avelumab in combination with chemotherapy as first-line treatment of adult patients with locally advanced or metastatic solid tumors. Initially, avelumab will be evaluated in combination with pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung cancer (NSCLC) (Cohort A1) and in combination with gemcitabine and cisplatin in patients with cisplatin-eligible urothelial (bladder) cancer (UC) (Cohort A2). As more information is learned about other anti-cancer immunotherapy agents, in future portions of the study, avelumab may be combined with chemotherapy and other anti-cancer immunotherapy agents in patients with these same or different tumor types.
This is a Phase 1b/2, open label, multicenter, safety, clinical activity, pharmacokinetic (PK), and pharmacodynamics (PD) study of avelumab in combination with chemotherapy with or without other anti-cancer immunotherapies, as first-line treatment of adult patients with locally advanced or metastatic solid tumors. Initially, avelumab will be evaluated in combination with pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung cancer (NSCLC) (Cohort A1) and with gemcitabine and cisplatin in patients with cisplatin-eligible urothelial cancer (UC) (Cohort A2).
Given the growing preclinical and clinical indications that combinations of anti-cancer immunotherapies potentially improve patient outcomes compared to results seen with single agents, in portions of the study to be added in the future, avelumab will be evaluated in combination with both standard-of-care chemotherapy and other anti-cancer immunotherapies in patients with advanced malignancies. Each cohort in the study will consist of a Phase 1b lead-in portion to evaluate safety and a Phase 2 cohort expansion to evaluate safety and efficacy.
In the Phase 1b safety lead-in portion, up to 12 patients will be enrolled into each cohort and evaluated for dose-limiting toxicities (DLT) during the first 2 cycles of treatment. If investigational products administration in a cohort is deemed safe in the Phase 1b lead-in, enrollment may be expanded into the Phase 2 cohort expansion. Up to approximately 40 patients in each cohort (including those enrolled in the Phase 1b lead-in and those enrolled in the Phase 2 cohort expansion) will be enrolled and treated with avelumab plus chemotherapy in the initial portion of the study and, in future portions of the study, with avelumab plus chemotherapy with or without other anti-cancer immunotherapies.
In the Phase 1b lead-in portions of NSCLC Cohort A1 and UC Cohort A2, avelumab is dosed at 800 mg fixed dose every 3 weeks. Under Protocol Amendment 4, avelumab is dosed at 1200 mg fixed dose every 3 weeks in the Phase 1b lead-in portions of NSCLC Cohort A3 and in UC Cohort A4, in combination with the same standard-of-care chemotherapy doublets used in Cohort A1 and Cohort A2, respectively. For each tumor type, the study treatment combination with the highest avelumab dose determined to be safe may be advanced into Phase 2 cohort expansion.
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.
Histological diagnosis of locally advanced (primary or recurrent) or solid tumor that is not amenable for treatment with curative intent as follows:
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.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
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.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
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.
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.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
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.
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.
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.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
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.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
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.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
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.
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.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
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.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
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.
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.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
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.
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.
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.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
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.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
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.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
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.
Non-squamous non-small cell lung cancer (NSCLC) patients treated with 800 mg avelumab plus pemetrexed/carboplatin
Drug: Avelumab 800 mg in combination with pemetrexed / carboplatin
Cisplatin-eligible urothelial cancer (UC)patients treated with 800 mg avelumab plus gemcitabine/cisplatin
Drug: Avelumab 800 mg in combination with gemcitabine / cisplatin.
Non-squamous non-small cell lung cancer (NSCLC) patients treated with 1200 mg avelumab plus pemetrexed/carboplatin
Drug: Avelumab 1200 mg in combination with pemetrexed/carboplatin
Cisplatin-eligible urothelial cancer (UC) patients treated with 1200 mg avelumab plus gemcitabine/cisplatin
Drug: Avelumab 1200 mg in combination with gemcitabine/cisplatin
Drug page: Avelumab
Avelumab Pemetrexed Carboplatin
Drug page: Avelumab
Avelumab Gemcitabine Cisplatin
Drug page: Avelumab
Avelumab Pemetrexed Carboplatin
Drug page: Avelumab
Avelumab Gemcitabine Cisplatin
Phase 1b Lead-in: Number of Participants With Dose-Limiting Toxicities (DLT)
DLTs=occurrence of any AEs attributable to study treatment in first 2 treatment cycles:Hematologic: grade(G)4 neutropenia lasting \>7days;febrile neutropenia with body temperature \>=38 degree Celsius for \>1hour; G\>=3 neutropenic infection(absolute neutrophil count \<1.0\*10\^9/L),G\>=3 thrombocytopenia (platelet count\<50.0-25.0\*10\^9/L)with bleeding;G4 thrombocytopenia(PC\<25.0\*10\^9/L),G4 anemia(life-threatening).Non-hematologic: any G4 toxicities;G3 toxicities persisting for \>3days despite medical treatment(nausea,vomiting,diarrhea)except endocrinopathies controlled with hormonal therapy;ALT/AST \>3\*upper limit of normal(ULN)if normal at baseline or 2\*Baseline(\>ULN at baseline)with total bilirubin \>2\*ULN and alkaline phosphatase \<2\*ULN;G3 QTcF prolongation after correction of any reversible cause(electrolyte abnormalities/hypoxia).Delay of \>=3weeks in scheduled administration/failure to deliver 75% of doses due to toxicities attributable to any study treatment. DLT-evaluable analysis set.
Time frame: Day 1 up to Week 6 (first 2 treatment cycles; 1 cycle = 21 days)
Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment
OR: complete response(CR) or partial response(PR)determined by investigator according to RECIST v1.1 from date of first dose of study treatment until date of first documentation of progressive disease(PD),confirmed by repeat assessments performed no less than 4 weeks after first response. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD.
Time frame: From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately)
Serum Concentration of Avelumab
The lower limit of quantification (LLOQ) for avelumab was 0.2 micrograms per milliliter. Pharmacokinetic concentration analysis set was subset of safety analysis set and included participants who had at least one concentration measurement for avelumab or other study drugs which they were assigned to receive. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.
Time frame: Pre-dose, 1 hour post-dose on Day 1 of Cycle 1, 2, 3, 6, 10, 14; 336 hours post-dose on Day 15 of Cycle 1, 2, 3 (each cycle of 21 days)
Absolute Value of Tumor Mutational Burden (TMB) in Tumor Tissue
Mutational load within tumor tissue was defined as number per megabase of the genome, coding, base substitution, and indel mutations present in the sample. Mutational load was determined in whole blood samples using next generation deoxyribonucleic acid (DNA) sequencing followed by computational analysis.
Time frame: Pre-dose on Day 1 of Cycle 1
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Adverse event (AE) was any untoward medical occurrence in a participants who received any study drug without regard to possibility of causal relationship. Serious adverse event was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. 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 years approximately)
Number of Participants With Treatment Related TEAEs
A treatment related AE included AEs related to at least one study drug 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. Relatedness to study drug was assessed by the investigator.
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 years approximately)
Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03
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 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 years approximately)
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade
Participants with laboratory abnormalities of any Grade as per NCI CTCAE toxicity grading v4.03 were summarized:hematology(anemia,hemoglobin increased,lymphocyte count decreased,lymphocyte count increased, neutrophil count decreased,platelet count decreased and white blood cell decreased)and clinical chemistry(alanine aminotransferase increased,alkaline phosphatase,increased,aspartate,aminotransferase increased,blood bilirubin increased,cholesterol high,creatinine phosphokinase\[cpk\] increased,creatinine increased,gamma-glutamyl transferase\[ggt\] increased,hypercalcemia,hyperglycemia,hyperkalemia, hypermagnesemia,hypernatremia,hypertriglyceridemia,hypoalbuminemia,hypocalcemia,hypoglycemia,hypokalemia,hypomagnesemia,hyponatremia, hypophosphatemia,serum amylase increased and lipase increased).As per NCI CTCAE toxicity grading v4.03, Grade1=mild;Grade2=moderate;Grade3=severe;Grade4=life-threatening;Grade 5=death.Parameters with at least 1 participant with abnormal value are reported.
Time frame: From screening up to 90 days after last dose of study drug (maximum up to 5 years approximately)
Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies for Avelumab
Blood samples were collected for assessment of avelumab ADAs using a tiered assay and confirmed positive samples were tested for neutralizing antibodies (nAb).
Time frame: From first dose of study drug up to last dose of study drug (maximum up to 5 years approximately)
Progression Free Survival (PFS) as Per RECIST v 1.1 by Investigator Assessment
PFS was defined as the time from the date of first dose of study treatment to the date of the first documentation of PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. The median duration of PFS was not derived for less than (\<) 10 participants.
Time frame: From start of treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 5 years approximately)
Overall Survival (OS)
OS was defined as the time from the first dose of study treatment to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact. The median duration of OS was not derived for less than (\<) 10 participants.
Time frame: From first dose of study treatment until death due to any cause (maximum up to 5 years approximately)
Duration of Response (DOR) as Per RECIST v 1.1 by Investigator Assessment
DOR was defined as time from first documentation of objective response (confirmed CR or PR) to the date of first PD documentation or death due to any cause, whichever occurs first. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. Median DOR was not derived for \< 5 participants.
Time frame: From date of first documented response to date of first documented PD or death due to any cause, whichever occurred first (maximum up to 5 years approximately)
Time-to-Tumor Response (TTR) as Per RECIST v 1.1 by Investigator Assessment
TTR was defined as the time from the date of first dose of study treatment to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD.
Time frame: From first dose of study treatment until first documentation of CR or PR (maximum up to 5 years approximately)
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression
PD-L1 expression was determined using the Ventana PD-L1 SP263 IHC assay. PD-L1-positive status in UC cohorts was defined using an algorithm that combines assessments of PD-L1 staining on tumor and immune cells scored by pathologists and in NSCLC cohorts was defined as PD-L1 expression on \>=1% of tumor cells. PD-L1 expression at baseline and on-treatment were reported in this outcome measure.
Time frame: Baseline and Cycle 2 Day 8 (each cycle of 21 days)
The study was conducted in 2 phases: Phase 1b (lead-in phase) and Phase 2 (cohort expansion phase). Phase 2 was conducted at the highest dose level of avelumab which was determined safe for participants in Phase 1b.
| Milestone | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 1200 mg + Gemcitabine/Cisplatin | Phase 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|---|
| Started | 6 | 13 | 6 | 6 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 6 | 13 | 6 | 6 | 0 |
| Withdrew: Adverse event | 3 | 4 | 1 | 1 | 0 |
| Withdrew: Physician decision | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Death | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Progressive disease | 1 | 6 | 3 | 4 | 0 |
| Withdrew: Other | 2 | 1 | 0 | 0 | 0 |
| Withdrew: Global deterioration of health status | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Study terminated by sponsor | 0 | 1 | 0 | 1 | 0 |
| Milestone | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 1200 mg + Gemcitabine/Cisplatin | Phase 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|---|
| Started | 6 | 12 | 5 | 6 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 6 | 12 | 5 | 6 | 0 |
| Withdrew: Death | 3 | 8 | 4 | 4 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Other | 0 | 1 | 0 | 1 | 0 |
| Withdrew: Study terminated by sponsor | 2 | 3 | 0 | 1 | 0 |
| Milestone | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 1200 mg + Gemcitabine/Cisplatin | Phase 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 35 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 35 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 6 |
| Withdrew: Progressive disease | 0 | 0 | 0 | 0 | 22 |
| Withdrew: Other | 0 | 0 | 0 | 0 | 4 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Physician decision | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 1 |
| Milestone | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 1200 mg + Gemcitabine/Cisplatin | Phase 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 33 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 33 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 24 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Other | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 0 | 0 | 7 |
The lower limit of quantification (LLOQ) for avelumab was 0.2 micrograms per milliliter. Pharmacokinetic concentration analysis set was subset of safety analysis set and included participants who had at least one concentration measurement for avelumab or other study drugs which they were assigned to receive. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.
| Micrograms per milliliter | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Cycle 1/Day 1- 1 hour | 173.3 ± 26 | 172.2 ± 18 | 284.1 ± 33 | 300.2 ± 32 |
| Cycle 1/Day 15- 336 hours | 12.32 ± 47 | 9.570 ± 92 | 16.51 ± 68 | 14.71 ± 74 |
| Cycle 2/Day 1- pre-dose | 4.780 ± 44 | 3.754 ± 115 | 4.328 ± 332 | 5.013 ± 196 |
| Cycle 2/Day 1- 1 hour | 164.2 ± 33 | 197.0 ± 18 | 104.5 ± 1474 | 311.9 ± 36 |
| Cycle 2/Day 15- 336 hours | 16.87 ± 24 | 13.55 ± 33 | 16.82 ± 137 | 18.66 ± 75 |
| Cycle 3/Day 1- pre-dose | 8.122 ± 40 | 5.651 ± 75 | 4.878 ± 662 | 6.771 ± 104 |
| Cycle 3/Day 1- 1 hour | 147.0 ± 35 | 204.0 ± 28 | 93.81 ± 2989 | 296.8 ± 36 |
| Cycle 3/Day 15- 336 hours | 19.40 ± 14 | 17.15 ± 40 | 26.17 ± 74 | 22.55 ± 79 |
| Cycle 6/Day 1- pre-dose | 11.38 ± 24 | 9.518 ± 65 | 10.86 ± 165 | 10.39 ± 233 |
| Cycle 6/Day 1- 1 hour | 92.53 ± 203 | 208.3 ± 23 | 245.4 ± 6 | 344.0 ± 27 |
| Cycle 10/Day 1- pre-dose | 9.523 ± 33 | 8.695 ± 115 | 6.620 ± NA | 18.55 ± 58 |
| Cycle 10/Day 1- 1 hour | 179.0 ± 38 | 222.0 ± 27 | 6.040 ± NA | 242.9 ± 121 |
| Cycle 14/Day 1- pre-dose | 14.97 ± 28 | 13.37 ± 77 | 12.24 ± 523 | 16.49 ± 57 |
| Cycle 14/Day 1- 1 hour | 215.3 ± 20 | 216.6 ± 22 | 29.05 ± 20555 | 402.2 ± 19 |
Mutational load within tumor tissue was defined as number per megabase of the genome, coding, base substitution, and indel mutations present in the sample. Mutational load was determined in whole blood samples using next generation deoxyribonucleic acid (DNA) sequencing followed by computational analysis.
| Mutations per megabase | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Absolute Value of Tumor Mutational Burden (TMB) in Tumor Tissue | 4.3 ± 6.75 | 2.8 ± 2.76 | 4.4 ± 5.15 | 2.5 ± 2.88 |
DLTs=occurrence of any AEs attributable to study treatment in first 2 treatment cycles:Hematologic: grade(G)4 neutropenia lasting \>7days;febrile neutropenia with body temperature \>=38 degree Celsius for \>1hour; G\>=3 neutropenic infection(absolute neutrophil count \<1.0\*10\^9/L),G\>=3 thrombocytopenia (platelet count\<50.0-25.0\*10\^9/L)with bleeding;G4 thrombocytopenia(PC\<25.0\*10\^9/L),G4 anemia(life-threatening).Non-hematologic: any G4 toxicities;G3 toxicities persisting for \>3days despite medical treatment(nausea,vomiting,diarrhea)except endocrinopathies controlled with hormonal therapy;ALT/AST \>3\*upper limit of normal(ULN)if normal at baseline or 2\*Baseline(\>ULN at baseline)with total bilirubin \>2\*ULN and alkaline phosphatase \<2\*ULN;G3 QTcF prolongation after correction of any reversible cause(electrolyte abnormalities/hypoxia).Delay of \>=3weeks in scheduled administration/failure to deliver 75% of doses due to toxicities attributable to any study treatment. DLT-evaluable analysis set.
| Participants | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Phase 1b Lead-in: Number of Participants With Dose-Limiting Toxicities (DLT) | 0 | 1 | 0 | 1 |
OR: complete response(CR) or partial response(PR)determined by investigator according to RECIST v1.1 from date of first dose of study treatment until date of first documentation of progressive disease(PD),confirmed by repeat assessments performed no less than 4 weeks after first response. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD.
| Percentage of Participants | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment | 50.0 ± 11.8 | 53.8 ± 25.1 | 33.3 ± 4.3 | 39.0 ± 24.2 |
Adverse event (AE) was any untoward medical occurrence in a participants who received any study drug without regard to possibility of causal relationship. Serious adverse event was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. 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 Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| TEAEs | 6 | 13 | 6 | 40 |
| Serious TEAEs | 3 | 9 | 5 | 20 |
A treatment related AE included AEs related to at least one study drug 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. Relatedness to study drug was assessed by the investigator.
| Participants | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Number of Participants With Treatment Related TEAEs | 6 | 12 | 6 | 40 |
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 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 Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03 | 5 | 12 | 6 | 37 |
Participants with laboratory abnormalities of any Grade as per NCI CTCAE toxicity grading v4.03 were summarized:hematology(anemia,hemoglobin increased,lymphocyte count decreased,lymphocyte count increased, neutrophil count decreased,platelet count decreased and white blood cell decreased)and clinical chemistry(alanine aminotransferase increased,alkaline phosphatase,increased,aspartate,aminotransferase increased,blood bilirubin increased,cholesterol high,creatinine phosphokinase\[cpk\] increased,creatinine increased,gamma-glutamyl transferase\[ggt\] increased,hypercalcemia,hyperglycemia,hyperkalemia, hypermagnesemia,hypernatremia,hypertriglyceridemia,hypoalbuminemia,hypocalcemia,hypoglycemia,hypokalemia,hypomagnesemia,hyponatremia, hypophosphatemia,serum amylase increased and lipase increased).As per NCI CTCAE toxicity grading v4.03, Grade1=mild;Grade2=moderate;Grade3=severe;Grade4=life-threatening;Grade 5=death.Parameters with at least 1 participant with abnormal value are reported.
| Participants | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| ALANINE AMINOTRANSFERASE INCREASED | 1 | 1 | 0 | 3 |
| ALKALINE PHOSPHATASE INCREASED | 0 | 0 | 0 | 1 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 1 | 1 | 0 | 2 |
| BLOOD BILIRUBIN INCREASED | 0 | 1 | 0 | 0 |
| CPK INCREASED | 0 | 0 | 0 | 1 |
| CREATININE INCREASED | 1 | 1 | 0 | 0 |
| GGT INCREASED | 0 | 2 | 1 | 4 |
| HYPERGLYCEMIA | 2 | 2 | 0 | 4 |
| HYPERKALEMIA | 0 | 1 | 0 | 2 |
| HYPOKALEMIA | 1 | 0 | 0 | 5 |
| HYPONATREMIA | 0 | 2 | 1 | 4 |
| LIPASE INCREASED | 1 | 2 | 1 | 4 |
| SERUM AMYLASE INCREASED | 0 | 2 | 0 | 4 |
| HYPOPHOSPHATEMIA | 2 | 0 | 1 | 3 |
| HYPOMAGNESEMIA | 0 | 0 | 0 | 2 |
| HYPOCALCEMIA | 2 | 0 | 0 | 1 |
| HYPERTRIGLYCERIDEMIA | 0 | 3 | 0 | 2 |
| HYPERNATREMIA | 0 | 0 | 0 | 1 |
| HYPERMAGNESEMIA | 0 | 0 | 0 | 1 |
| HYPERCALCEMIA | 0 | 0 | 0 | 1 |
| ANEMIA | 2 | 5 | 0 | 6 |
| LYMPHOCYTE COUNT DECREASED | 3 | 5 | 1 | 7 |
| LYMPHOCYTE COUNT INCREASED | 0 | 0 | 0 | 1 |
| NEUTROPHIL COUNT DECREASED | 3 | 8 | 3 | 21 |
| PLATELET COUNT DECREASED | 3 | 2 | 0 | 11 |
| WHITE BLOOD CELL DECREASED | 2 | 7 | 3 | 16 |
Blood samples were collected for assessment of avelumab ADAs using a tiered assay and confirmed positive samples were tested for neutralizing antibodies (nAb).
| Participants | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| ADA ever positive | 0 | 5 | 1 | 9 |
| NAB ever positive | NA | NA | NA | NA |
PFS was defined as the time from the date of first dose of study treatment to the date of the first documentation of PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. The median duration of PFS was not derived for less than (\<) 10 participants.
| Months | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Progression Free Survival (PFS) as Per RECIST v 1.1 by Investigator Assessment | NA (NA to NA) | 9.8 (2.2 to NA) | NA (NA to NA) | 5.4 (2.9 to 6.0) |
OS was defined as the time from the first dose of study treatment to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact. The median duration of OS was not derived for less than (\<) 10 participants.
| Months | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Overall Survival (OS) | NA (NA to NA) | 18.1 (5.0 to NA) | NA (NA to NA) | 15.1 (8.7 to 22.0) |
DOR was defined as time from first documentation of objective response (confirmed CR or PR) to the date of first PD documentation or death due to any cause, whichever occurs first. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. Median DOR was not derived for \< 5 participants.
| Months | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Duration of Response (DOR) as Per RECIST v 1.1 by Investigator Assessment | NA (NA to NA) | 9.6 (4.0 to NA) | NA (NA to NA) | NA (4.2 to NA) |
TTR was defined as the time from the date of first dose of study treatment to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD.
| Months | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Time-to-Tumor Response (TTR) as Per RECIST v 1.1 by Investigator Assessment | 2.8 ± 1.3 | 1.4 ± 1.1 | 1.3 ± 1.3 | 1.5 ± 1.3 |
PD-L1 expression was determined using the Ventana PD-L1 SP263 IHC assay. PD-L1-positive status in UC cohorts was defined using an algorithm that combines assessments of PD-L1 staining on tumor and immune cells scored by pathologists and in NSCLC cohorts was defined as PD-L1 expression on \>=1% of tumor cells. PD-L1 expression at baseline and on-treatment were reported in this outcome measure.
| Participants | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Baseline- Positive PD-L1 | 0 | 6 | 1 | 28 |
| Baseline- Negative PD-L1 | 4 | 7 | 4 | 13 |
| Baseline- Unknown PD-L1 | 2 | 0 | 1 | 0 |
| On-treatment (Cycle 2 Day 8)- Positive PD-L1 | 0 | 2 | 1 | 3 |
| On-treatment (Cycle 2 Day 8)- Negative PD-L1 | 2 | 1 | 0 | 6 |
| On-treatment (Cycle 2 Day 8)- Unknown PD-L1 | 4 | 10 | 5 | 32 |
Collected over All-cause mortality: From start of the treatment up to 90 days post last dose of study treatment (maximum of 5 years approximately), TEAEs and Serious TEAEs: From start of the treatment up to 30 days post last dose of study treatment. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | 3/6 (50%) | 3/6 (50%) | 6/6 (100%) |
| Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | 8/13 (61.5%) | 9/13 (69.2%) | 13/13 (100%) |
| Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | 5/6 (83.3%) | 5/6 (83.3%) | 6/6 (100%) |
| Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin | 29/41 (70.7%) | 20/41 (48.8%) | 40/41 (97.6%) |
| Event | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| PneumonitisRespiratory, thoracic and mediastinal disorders | 0/6 | 0/13 | 2/6 | 0/41 |
| DiarrhoeaGastrointestinal disorders | 1/6 | 1/13 | 0/6 | 0/41 |
| IleusGastrointestinal disorders | 0/6 | 0/13 | 1/6 | 0/41 |
| SubileusGastrointestinal disorders | 0/6 | 0/13 | 1/6 | 0/41 |
| Rectal abscessInfections and infestations | 0/6 | 0/13 | 1/6 | 0/41 |
| FasciitisMusculoskeletal and connective tissue disorders | 0/6 | 0/13 | 1/6 | 0/41 |
| HydrocephalusNervous system disorders | 0/6 | 0/13 | 1/6 | 0/41 |
| Acute kidney injuryRenal and urinary disorders | 1/6 | 1/13 | 0/6 | 0/41 |
| Near drowningInjury, poisoning and procedural complications | 1/6 | 0/13 | 0/6 | 0/41 |
| Myocardial infarctionCardiac disorders | 0/6 | 2/13 | 0/6 | 0/41 |
| Event | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 3/6 | 10/13 | 1/6 | 26/41 |
| NauseaGastrointestinal disorders | 3/6 | 9/13 | 4/6 | 19/41 |
| NeutropeniaBlood and lymphatic system disorders | 3/6 | 8/13 | 4/6 | 23/41 |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/6 | 4/13 | 4/6 | 20/41 |
| Platelet count decreasedInvestigations | 4/6 | 4/13 | 1/6 | 9/41 |
| FatigueGeneral disorders | 3/6 | 8/13 | 3/6 | 15/41 |
| DiarrhoeaGastrointestinal disorders | 2/6 | 4/13 | 3/6 | 8/41 |
| Blood creatinine increasedInvestigations | 3/6 | 2/13 | 0/6 | 13/41 |
| HypophosphataemiaMetabolism and nutrition disorders | 3/6 | 0/13 | 0/6 | 2/41 |
| ConstipationGastrointestinal disorders | 0/6 | 4/13 | 1/6 | 17/41 |
| Age, Categorical(Participants) | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 1 | 7 | 3 | 14 | 25 |
| >=65 years | 5 | 6 | 3 | 27 | 41 |
| Sex: Female, Male(Participants) | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin | Total |
|---|---|---|---|---|---|
| Female | 2 | 5 | 0 | 10 | 17 |
| Male | 4 | 8 | 6 | 31 | 49 |
| Ethnicity (NIH/OMB)(Participants) | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 0 | 0 | 1 |
| Not Hispanic or Latino | 6 | 11 | 6 | 37 | 60 |
| Unknown or Not Reported | 0 | 1 | 0 | 4 | 5 |
| Race (NIH/OMB)(Participants) | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 | 1 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 0 | 0 | 1 |
| White | 6 | 11 | 5 | 37 | 59 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 3 | 3 |
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 Dec 2017 to primary completion in Jun 2021, 41 months.
Results were first posted in Jun 2022, 1 year after primary completion.
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This study is terminated, as verified in Aug 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Avelumab
Carcinoma, Non-Small-Cell Lung →