A Phase 1 interventional study of Utomilumab and Trastuzumab in HER2 Positive Breast Carcinoma, Recurrent Breast Carcinoma and Stage III Breast Cancer, sponsored by George W. Sledge Jr.. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-10-19.
Sponsored by George W. Sledge Jr. · Phase 1, Interventional, and Treatment
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This trial studies the best dose and side effects of utomilumab (4-1BB agonist monoclonal antibody PF-05082566) with trastuzumab emtansine or trastuzumab in treating patients with HER2-positive breast cancer that has spread to other places in the body. Monoclonal antibodies, such as utomilumab, trastuzumab emtansine, and trastuzumab may interfere with the ability of tumor cells to grow and spread.
PRIMARY OBJECTIVE:
Estimate the maximum tolerated dose (MTD) and determine the recommended dose (RP2D) of utomilumab in combination with ado-rastuzumab emtansine (T-DM1) or trastuzumab in subjects with HER2-positive advanced breast cancer.
SECONDARY OBJECTIVES:
OUTLINE: Patients are randomized to 1 of 2 cohorts.
COHORT 1: Dose 1: Utomilumab 20 mg IV + ado-trastuzumab emtansine (T-DM1) 3.6 mg/kg IV every 3 weeks. Dose 2: Dose Level 2 - Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks
COHORT 2: Dose 1: Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. Dose Level 2 - Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
14,829 studies on the registry are indexed under Breast Neoplasms; 3,320 are open to participants now.
This study's enrollment of 18 is below the median of 72 across 10,903 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →This is the only study on the registry with George W. Sledge Jr. as lead sponsor.
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.
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.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
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.
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 number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
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.
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 share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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.
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.
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.
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.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask 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.
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.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
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.
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.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
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.
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.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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.
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.
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.
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.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask 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.
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
Drug: Utomilumab · Drug: Trastuzumab
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
Drug: Utomilumab · Drug: Trastuzumab
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
Drug: Utomilumab · Drug: Ado-Trastuzumab Emtansine
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
Drug: Utomilumab · Drug: Ado-Trastuzumab Emtansine
Given IV
Also known as: 4-1BB Agonist Monoclonal Antibody PF-05082566, PF-05082566, PF-2566
Given IV
Also known as: ABP 980, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, PF-05280014, rhuMAb HER2, RO0452317, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar PF-05280014
Given IV
Also known as: Trastuzumab Emtansine, Kadcyla, PRO132365, RO5304020, T-DM1, Trastuzumab-DM1, Trastuzumab-MCC-DM1, Trastuzumab-MCC-DM1 Antibody-Drug Conjugate, Trastuzumab-MCC-DM1 Immunoconjugate
Dose-limiting Toxicities (DLTs)
Dose-limiting toxicities (DLTs) within the first 2 cycles (6 weeks) of treatment were assessed. DLTs are treatment-related adverse events defined as: * Neutropenia Grade (Gr) 4 \>7 days * Febrile neutropenia, defined as absolute neutrophil count \<1000/mm3 with a single temperature of \>38.3 degrees C (101 degrees F) or a sustained temperature of ≥38 degrees C (100.4 degrees F) for \>1 hour * Neutropenic infection ≥Gr 3 * Thrombocytopenia ≥Gr 4, or with bleeding Gr 3 * Non-laboratory toxicities ≥Gr 3, except nausea, vomiting, or diarrhea recovering to \<Gr 2 within 48 hours. * Laboratory abnormalities \[other than aspartate aminotransferase / alanine aminotransferase (AST/ALT)\] ≥Gr 3, if: * Medical intervention required * Hospitalization required, or * \>24 hours * AST \& ALT Gr 4, or \>3×ULN * Total bilirubin \>2×ULN, with no elevation of alkaline phosphatase The outcome is reported as the number of DLTs observed per group, a number with dispersion.
Time frame: 6 weeks
Objective Tumor Response (ORR)
Objective tumor response (ORR) per RECIST v1.1 was assessed after 4 cycles (3 months) of treatment. RECIST v1.1 was assessed on target lesions as: * Complete Response (CR): Complete disappearance of all lesions with the exception of nodal disease. All target lymph nodes must decrease to normal size (short axis \< 10 mm). * Partial Response (PR): ≥ 30% decrease in the sum of diameters of all measurable lesions. * Progressive Disease (PD): Increase in lesion size ≥ 5 mm and ≥ 20% increase in the sum of diameters of measurable lesions. * Stable Disease (SD): All lesions assessed, but not CR, PR, or PD. Per protocol, the outcome is reported for participants in Cohort 2B (ado-trastuzumab emtansine + utomilumab) as the number of participants with the indicated clinical response, a number without dispersion.
Time frame: 3 months
Time-to-tumor Response (TTR)
Time-to-tumor response (TTR) was assessed per RECIST v1.1, in participants who have at least 1 on-study tumor assessment \& respond within 4 cycles (3 months). RECIST v1.1 was assessed as: * Complete Response (CR): Complete disappearance of target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \< 10 mm). * Partial Response (PR): ≥ 30% decrease in the sum of diameters of target measurable lesions. By definition, TTR an assessment of the tumor response, meaning a CR or a PR. Per protocol, the outcome is reported as the median with full range for participants in Cohort 2B (ado-trastuzumab emtansine + utomilumab) achieving a clinical response within 4 cycles (3 months).
Time frame: 3 months
Duration of Response (DoR)
Duration of response (DoR) was assessed in participants who have 1+ on-study tumor assessment(s) and have a clinical response, through up to 5 years after treatment. RECIST v1.1 was assessed as: * Complete Response (CR): Complete disappearance of target lesions with the exception of nodal disease. Target nodes must decrease to normal size (short axis \< 10 mm). * Partial Response (PR): ≥ 30% decrease in the sum of diameters of target measurable lesions. * Progression Disease (PD): Increase in lesion size ≥ 5 mm and ≥ 20% increase in the sum of diameters of target measurable lesions. * Stable Disease (SD): Target lesions assessed, but not CR, PR, or PD. By definition, DoR is an assessment of tumor response, meaning the participants achieved a CR or a PR. Per protocol, the outcome is reported as the median with full range for participants in Cohort 2B (ado-trastuzumab emtansine + utomilumab) achieving a clinical response within 5 years (260 weeks).
Time frame: up to 260 weeks
Progression-free Survival (PFS)
Progression-free survival (PFS) means the participants remained alive without disease progression (DP). DP was defined per RECIST v1.1 as an increase in lesion size ≥ 5 mm or ≥ 20% increase in the sum of diameters of target measurable lesions. The outcome is reported as the median time that participants survived without DP, with full range.
Time frame: 128 weeks
Adverse Events by Severity Grade 1 to 5
Adverse events while receiving treatment and within 30 days were assessed by treatment group for severity (as graded by NCI CTCAE v5). The outcome is reported by treatment group as the numbers of adverse events by treatment group, numbers without dispersion.
Time frame: Up to 128 weeks
Adverse Event Relationship to Study Drugs
Adverse events while receiving treatment and within 30 days were assessed by treatment group for relationship to the study treatments. The outcome is reported as the numbers of related adverse events by treatment group, numbers without dispersion.
Time frame: Up to 128 weeks
Laboratory Value Abnormalities
Adverse events that were laboratory value abnormalities that occurred during treatment or within 30 days, were assessed by treatment group. The outcome is reported as the number of laboratory abnormalities by treatment group that were laboratory value abnormalities (Yes) or not (No), numbers without dispersion.
Time frame: Up to 128 weeks
| Milestone | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|---|---|---|
| Started | 3 | 2 | 3 | 10 |
| Completed | 3 | 2 | 3 | 10 |
| Not completed | 0 | 0 | 0 | 0 |
Dose-limiting toxicities (DLTs) within the first 2 cycles (6 weeks) of treatment were assessed. DLTs are treatment-related adverse events defined as: * Neutropenia Grade (Gr) 4 \>7 days * Febrile neutropenia, defined as absolute neutrophil count \<1000/mm3 with a single temperature of \>38.3 degrees C (101 degrees F) or a sustained temperature of ≥38 degrees C (100.4 degrees F) for \>1 hour * Neutropenic infection ≥Gr 3 * Thrombocytopenia ≥Gr 4, or with bleeding Gr 3 * Non-laboratory toxicities ≥Gr 3, except nausea, vomiting, or diarrhea recovering to \<Gr 2 within 48 hours. * Laboratory abnormalities \[other than aspartate aminotransferase / alanine aminotransferase (AST/ALT)\] ≥Gr 3, if: * Medical intervention required * Hospitalization required, or * \>24 hours * AST \& ALT Gr 4, or \>3×ULN * Total bilirubin \>2×ULN, with no elevation of alkaline phosphatase The outcome is reported as the number of DLTs observed per group, a number with dispersion.
| Dose-limiting toxicities (DLTs) | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|---|---|---|
| Dose-limiting Toxicities (DLTs) | 0 | 0 | 0 | 0 |
Objective tumor response (ORR) per RECIST v1.1 was assessed after 4 cycles (3 months) of treatment. RECIST v1.1 was assessed on target lesions as: * Complete Response (CR): Complete disappearance of all lesions with the exception of nodal disease. All target lymph nodes must decrease to normal size (short axis \< 10 mm). * Partial Response (PR): ≥ 30% decrease in the sum of diameters of all measurable lesions. * Progressive Disease (PD): Increase in lesion size ≥ 5 mm and ≥ 20% increase in the sum of diameters of measurable lesions. * Stable Disease (SD): All lesions assessed, but not CR, PR, or PD. Per protocol, the outcome is reported for participants in Cohort 2B (ado-trastuzumab emtansine + utomilumab) as the number of participants with the indicated clinical response, a number without dispersion.
| participants | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|
| Complete Response (CR) | 0 |
| Partial Response (PR) | 1 |
| Progressive Disease (PD) | 5 |
| Stable Disease (SD) | 4 |
Time-to-tumor response (TTR) was assessed per RECIST v1.1, in participants who have at least 1 on-study tumor assessment \& respond within 4 cycles (3 months). RECIST v1.1 was assessed as: * Complete Response (CR): Complete disappearance of target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \< 10 mm). * Partial Response (PR): ≥ 30% decrease in the sum of diameters of target measurable lesions. By definition, TTR an assessment of the tumor response, meaning a CR or a PR. Per protocol, the outcome is reported as the median with full range for participants in Cohort 2B (ado-trastuzumab emtansine + utomilumab) achieving a clinical response within 4 cycles (3 months).
| weeks | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|
| Time-to-tumor Response (TTR) | 12 (12 to 12) |
Duration of response (DoR) was assessed in participants who have 1+ on-study tumor assessment(s) and have a clinical response, through up to 5 years after treatment. RECIST v1.1 was assessed as: * Complete Response (CR): Complete disappearance of target lesions with the exception of nodal disease. Target nodes must decrease to normal size (short axis \< 10 mm). * Partial Response (PR): ≥ 30% decrease in the sum of diameters of target measurable lesions. * Progression Disease (PD): Increase in lesion size ≥ 5 mm and ≥ 20% increase in the sum of diameters of target measurable lesions. * Stable Disease (SD): Target lesions assessed, but not CR, PR, or PD. By definition, DoR is an assessment of tumor response, meaning the participants achieved a CR or a PR. Per protocol, the outcome is reported as the median with full range for participants in Cohort 2B (ado-trastuzumab emtansine + utomilumab) achieving a clinical response within 5 years (260 weeks).
| weeks | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|
| Duration of Response (DoR) | 54 (45 to 63) |
Progression-free survival (PFS) means the participants remained alive without disease progression (DP). DP was defined per RECIST v1.1 as an increase in lesion size ≥ 5 mm or ≥ 20% increase in the sum of diameters of target measurable lesions. The outcome is reported as the median time that participants survived without DP, with full range.
| weeks | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|---|---|---|
| Progression-free Survival (PFS) | 9 (6 to 15) | 15 (12 to 17) | 45 (12 to 128) | 12 (3 to 85) |
Adverse events while receiving treatment and within 30 days were assessed by treatment group for severity (as graded by NCI CTCAE v5). The outcome is reported by treatment group as the numbers of adverse events by treatment group, numbers without dispersion.
| adverse events | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|---|---|---|
| CTCAE Grade 1 | 4 | 10 | 71 | 121 |
| CTCAE Grade 2 | 11 | 4 | 17 | 39 |
| CTCAE Grade 3 | 5 | 0 | 3 | 9 |
| CTCAE Grade 4 | 0 | 0 | 0 | 1 |
| CTCAE Grade 5 | 0 | 0 | 0 | 0 |
Adverse events while receiving treatment and within 30 days were assessed by treatment group for relationship to the study treatments. The outcome is reported as the numbers of related adverse events by treatment group, numbers without dispersion.
| adverse events | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|---|---|---|
| Not related | 3 | 2 | 14 | 24 |
| Unlikely related | 15 | 8 | 15 | 29 |
| Possibly related | 1 | 4 | 46 | 70 |
| Probably related | 1 | 0 | 11 | 49 |
| Definitely related | 0 | 0 | 5 | 0 |
Adverse events that were laboratory value abnormalities that occurred during treatment or within 30 days, were assessed by treatment group. The outcome is reported as the number of laboratory abnormalities by treatment group that were laboratory value abnormalities (Yes) or not (No), numbers without dispersion.
| adverse events | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|---|---|---|
| Yes | 1 | 2 | 18 | 18 |
| no | 18 | 12 | 73 | 152 |
Collected over 128 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1A (Trastuzumab + Utomilumab) | 0/3 (0%) | 1/3 (33.3%) | 2/3 (66.7%) |
| Cohort 1B (Trastuzumab + Utomilumab) | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) | 0/10 (0%) | 2/10 (20%) | 10/10 (100%) |
| Event | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|---|---|---|
| Abdominal painGastrointestinal disorders | 1/3 | 0/2 | 0/3 | 1/10 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 1/3 | 0/2 | 0/3 | 0/10 |
| AscitesGastrointestinal disorders | 0/3 | 0/2 | 0/3 | 1/10 |
| HyponatremiaMetabolism and nutrition disorders | 0/3 | 0/2 | 0/3 | 1/10 |
| Pleural hemorrhageRespiratory, thoracic and mediastinal disorders | 0/3 | 0/2 | 0/3 | 1/10 |
| Event | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) |
|---|---|---|---|---|
| NauseaGastrointestinal disorders | 1/3 | 2/2 | 0/3 | 4/10 |
| FatigueGeneral disorders | 1/3 | 1/2 | 3/3 | 6/10 |
| Flu-like symptomsGeneral disorders | 0/3 | 2/2 | 0/3 | 1/10 |
| Aspartate aminotransferase increasedInvestigations | 0/3 | 1/2 | 2/3 | 7/10 |
| PainGeneral disorders | 2/3 | 1/2 | 1/3 | 3/10 |
| White blood cell decreasedInvestigations | 0/3 | 0/2 | 2/3 | 1/10 |
| Vaginal hemorrhageReproductive system and breast disorders | 0/3 | 0/2 | 2/3 | 0/10 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/3 | 0/2 | 2/3 | 4/10 |
| AnemiaBlood and lymphatic system disorders | 0/3 | 0/2 | 1/3 | 5/10 |
| DiarrheaGastrointestinal disorders | 1/3 | 1/2 | 0/3 | 1/10 |
| Age, Categorical(Participants) | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 2 | 2 | 2 | 9 | 15 |
| >=65 years | 1 | 0 | 1 | 1 | 3 |
| Sex: Female, Male(Participants) | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) | Total |
|---|---|---|---|---|---|
| Female | 3 | 2 | 3 | 10 | 18 |
| Male | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 0 | 2 | 4 |
| Not Hispanic or Latino | 2 | 1 | 3 | 8 | 14 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 1 | 0 | 3 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 1 | 1 |
| Black or African American | 0 | 0 | 0 | 2 | 2 |
| White | 3 | 1 | 3 | 4 | 11 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Cohort 1A (Trastuzumab + Utomilumab) | Cohort 1B (Trastuzumab + Utomilumab) | Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab) | Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab) | Total |
|---|---|---|---|---|---|
| United States | 3 | 2 | 3 | 10 | 18 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Oct 2017 to primary completion in Feb 2021, 39 months.
Results were first posted in Oct 2022, 1 year 8 months after primary completion.
Of 372 non-industry phase 1 interventional studies under Breast Neoplasms, half reached primary completion within 48 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 77. This study's 39 months is below that.
Counting every sponsor, half of 761 studies reached it within 44 months; a quarter within 25 and three quarters within 65.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2022. You cannot join it, but the record below documents what was studied.
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