Head and Neck Cancer, Melanoma, Non Small Cell Lung Cancer, Urothelial Carcinoma
Conditions
Brief summary
The purpose of this study is to evaluate the safety of enoblituzumab (MGA271) in combination with Keytruda (pembrolizumab) when given to patients with B7-H3-expressing melanoma, squamous cell carcinoma of the head and neck (SCCHN), non small cell lung cancer (NSCLC), Urothelial Cancer and other B7-H3 expressing cancers. The study will also evaluate what is the highest dose of enoblituzumab that can be given safely when given with pembrolizumab. Assessments will also be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics) and to evaluate potential anti-tumor activity of MGA271 in combination with pembrolizumab. Safety and efficacy of enoblituzumab in combination with MGA012 (anti-PD-1 monoclonal antibody; also known as INCMGA00012) will also be evaluated.
Interventions
BIOLOGICALEnoblituzumab Schedule 1
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
BIOLOGICALPembrolizumab
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
BIOLOGICALEnoblituzumab Schedule 2
Enoblituzumab is administered by IV infusion every 3 weeks for up to 17 doses
BIOLOGICALretifanlimab
Retifanlimab is administered by IV infusion every 3 weeks for up to 17 doses
Sponsors
MacroGenics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* To enroll on cohorts 1-4, participants must have a histologically-proven, previously treated, unresectable, locally advanced or metastatic mesothelioma, urothelial cancer, thyroid cancer, pancreatic cancer, ovarian cancer, colon cancer, prostate cancer, soft tissue sarcoma, triple negative breast cancer, renal clear cell cancer, melanoma, squamous cell cancer of the head and neck, or non-small cell lung cancer. * Participants on the melanoma cohort must have progressed on or after at least one anti-PD-L1 or anti- PD-1 containing therapy. * Participants on the SCCHN cohort must have progressed on or after platinum-based systemic therapy * Participants on the NSCLC cohort must have progressed on or after first line systemic therapy * Participants on the urothelial cancer cohort must have received at least one platinum-containing regimen and have progressed on or after an anti-PD-L1 or anti-PD-1 containing therapy * Measurable disease per RECIST 1.1 criteria * Easter Cooperative Oncology Group (ECOG) performance status 0 or 1 * Acceptable laboratory parameters and adequate organ reserve.
Exclusion criteria
* Patients with a history of symptomatic central nervous system metastases, unless treated and asymptomatic * Patients with history of autoimmune disease with certain exceptions such as vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic therapy within the past 2 years, patients with history of Grave's disease that are now euthyroid clinically and by lab testing * History of allogeneic bone marrow, stem cell, or solid organ transplant * Treatment with systemic cancer therapy or investigational therapy within 4 weeks of first study drug administration; radiation within 2 weeks; corticosteroids (greater than or equal to 10 mg prednisone or equivalent per day) or other immune suppressive drugs within 2 weeks of first study drug administration * Trauma or major surgery within 4 weeks of first study drug administration * History of clinically-significant cardiovascular disease; gastrointestinal perforation; gastrointestinal bleeding, acute pancreatitis or diverticulitis within 4 weeks of first study drug administration * Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days of first study drug administration * Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction (PCR) * Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome * Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the drug or vehicle formulation for MGA271 or pembrolizumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab | Study Day 1-42, for Cohorts 1-4. | Dose-limiting toxicities are severe side effects related to study treatment that may cause dose interruptions, dose reductions, or withdrawal of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Trough Concentration of Enoblituzumab | At baseline, and Day 7. | Trough concentration is the concentration measured before the a subsequent dose of enoblituzumab. MGA271 is characterized by a biphasic concentration-time profile and PPK was used to estimate PK parameters at each dose level |
| Mean Area Under the Concentration Time Curve (AUC) From Time 0 to Day 7 of Enoblituzumab | At baseline, 1, 4, 24, 72 hours, and Day 7. | AUC is the total body exposure to enoblituzumab MGA271 is characterized by a biphasic concentration-time profile and PPK was used to estimate PK parameters at each dose level |
| Mean Clearance of Enoblituzumab | At baseline, 1, 4, 24, 72 hours, and Day 7. | Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time. |
| Mean Volume of Distribution at Steady State of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab | At baseline, 1, 4, 24, and 72 and Day 7. | The volume of distribution is related to how much drug is distributed to body tissues, or remains in the bloodstream |
| Mean Terminal Half-life of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab | At baseline, 1, 4, 24, and 72 and Day 7. | Terminal half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium MGA271 is characterized by a biphasic concentration-time profile and PPK was used to estimate PK parameters at each dose level |
| Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Every 3 weeks throughout the study, average duration 13 months. | — |
| Number of Participants That Develop Retifanlimab ADA | Every 3 weeks throughout the study, average duration 13 months. | — |
| Objective Response Rate | Six weeks after the first dose, then every 9 weeks throughout study until discontinuation, average 13 months | The number of participants with a complete response (CR) or partial response (PR) to enoblituzumab in combination with pembrolizumab or retifanlimab RECIST 1.1 criteria. |
| Mean Maximum Concentration of Enoblituzumab | Baseline, 1, 4, 24, and 72 hours after the first dose. | The highest measured concentration of enoblizuzumab in the bloodstream. |
| Best Overall Response (RECIST 1.1) | Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months. | The participants best response to treatment during their study participation. Responses are categorized as CR, PR, stable disease (SD), progressive disease (PD) or not evaluated (NE) |
| Best Overall Response (irRECIST 1.1) | Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months. | The participants best response to treatment during their study participation. Responses are categorized as CR, PR, stable disease (SD), progressive disease (PD) or not evaluated (NE) |
| Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average13 months. | The duration of response displays the minimum and maximum range in months from the first documented CR or PR until disease progression or death, whichever is first. |
| Minimum and Maximum DoR Per RECIST 1.1 | Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months. | The duration of response displays the minimum and maximum range in months from the first documented CR or PR until disease progression or death, whichever is first. |
| Median Progression-free Survival (PFS) Using RECIST 1.1 | Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months. | The time from the first infusion of pembrolizumab or retifanlimab until documented disease progression or death from any cause. |
| Median PFS Using irRECIST 1.1 Criteria | Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months. | The time from the first infusion of pembrolizumab or retifanlimab until documented disease progression or death from any cause. |
| Median Overall Survival | Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months. | The time from the first infusion of pembrolizumab or retifanlimab until death from any cause. |
| ORR Using Immune-related (ir) RECIST Criteria | Six weeks after the first dose, then every 9 weeks throughout study until discontinuation, average 13 months | The number of participants with a complete response (CR) or partial response (PR) to enoblituzumab in combination with pembrolizumab or retifanlimab using irRECIST 1.1 criteria. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 enoblituzumab 3 mg/kg IV weekly for up to 51 doses and pembrolizumab 2 mg/kg IV every 3 weeks for up to 17 doses | 6 |
| Cohort 2 enoblituzumab 10 mg/kg IV weekly for up to 51 doses and pembrolizumab 2 mg/kg IV every 3 weeks for up to 17 doses | 3 |
| Cohort 3 enoblituzumab 15 mg/kg IV weekly for up to 51 doses and pembrolizumab 2 mg/kg IV every 3 weeks for up to 17 doses | 3 |
| Melanoma Expansion enoblituzumab 15 mg/kg IV weekly for up to 51 doses and pembrolizumab 2 mg/kg IV every 3 weeks for up to 17 doses | 17 |
| Urothelial Cancer Expansion enoblituzumab 15 mg/kg IV weekly for up to 51 doses and pembrolizumab 2 mg/kg IV every 3 weeks for up to 17 doses | 21 |
| NSCLC Expansion enoblituzumab 15 mg/kg IV weekly for up to 51 doses and pembrolizumab 2 mg/kg IV every 3 weeks for up to 17 doses | 40 |
| SCCHN Expansion enoblituzumab 15 mg/kg IV weekly for up to 51 doses and pembrolizumab 2 mg/kg IV every 3 weeks for up to 17 doses | 43 |
| Cohort 4 enoblituzumab 15 mg/kg IV and retifanlimab 375 mg IV every three weeks for up to 17 doses.. | 12 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 | 1 | 1 | 4 | 6 | 2 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 3 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 1 | 0 | 0 | 1 | 4 | 0 |
| Overall Study | Progressive Disease | 3 | 2 | 2 | 13 | 15 | 25 | 30 | 10 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Total | Cohort 4 | SCCHN Expansion | NSCLC Expansion | Urothelial Cancer Expansion | Melanoma Expansion | Cohort 3 | Cohort 2 |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 7.85 | 63.8 years STANDARD_DEVIATION 11.06 | 62.4 years STANDARD_DEVIATION 12.09 | 62.7 years STANDARD_DEVIATION 9.63 | 64.8 years STANDARD_DEVIATION 8.2 | 67.2 years STANDARD_DEVIATION 9.24 | 62.9 years STANDARD_DEVIATION 14.92 | 74.7 years STANDARD_DEVIATION 14.64 | 41.7 years STANDARD_DEVIATION 25.38 |
| B7H3 immunohistochemistry status Negative | 0 Participants | 15 Participants | 3 Participants | 5 Participants | 3 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants |
| B7H3 immunohistochemistry status Positive | 4 Participants | 116 Participants | 9 Participants | 37 Participants | 32 Participants | 15 Participants | 16 Participants | 2 Participants | 1 Participants |
| B7H3 immunohistochemistry status Unknown | 2 Participants | 14 Participants | 0 Participants | 1 Participants | 5 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants |
| ECOG Performance Status ECOG 0 | 2 Participants | 39 Participants | 4 Participants | 13 Participants | 8 Participants | 5 Participants | 5 Participants | 1 Participants | 1 Participants |
| ECOG Performance Status ECOG 1 | 4 Participants | 103 Participants | 8 Participants | 29 Participants | 32 Participants | 16 Participants | 10 Participants | 2 Participants | 2 Participants |
| ECOG Performance Status Not reported | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 136 Participants | 10 Participants | 41 Participants | 37 Participants | 21 Participants | 16 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Height | 164.34 Centimeters STANDARD_DEVIATION 10.12 | 171.8 Centimeters STANDARD_DEVIATION 9.72 | 167.0 Centimeters STANDARD_DEVIATION 15.93 | 175.3 Centimeters STANDARD_DEVIATION 6.31 | 169.4 Centimeters STANDARD_DEVIATION 9.62 | 173.4 Centimeters STANDARD_DEVIATION 9.18 | 173.0 Centimeters STANDARD_DEVIATION 10.41 | 170.4 Centimeters STANDARD_DEVIATION 7.66 | 168.5 Centimeters STANDARD_DEVIATION 6.44 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 12 Participants | 3 Participants | 6 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 5 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 126 Participants | 8 Participants | 34 Participants | 36 Participants | 19 Participants | 17 Participants | 3 Participants | 3 Participants |
| Region of Enrollment Australia | 0 participants | 17 participants | 3 participants | 7 participants | 2 participants | 2 participants | 3 participants | 0 participants | 0 participants |
| Region of Enrollment Canada | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment United States | 6 participants | 126 participants | 9 participants | 36 participants | 37 participants | 19 participants | 14 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 3 Participants | 47 Participants | 6 Participants | 5 Participants | 18 Participants | 6 Participants | 6 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 98 Participants | 6 Participants | 38 Participants | 22 Participants | 15 Participants | 11 Participants | 2 Participants | 1 Participants |
| Weight | 73.2 Kilograms STANDARD_DEVIATION 8.67 | 78.0 Kilograms STANDARD_DEVIATION 19.43 | 91.1 Kilograms STANDARD_DEVIATION 35.44 | 75.6 Kilograms STANDARD_DEVIATION 13.6 | 74.4 Kilograms STANDARD_DEVIATION 17.15 | 82.7 Kilograms STANDARD_DEVIATION 17.63 | 81.5 Kilograms STANDARD_DEVIATION 24.82 | 79.0 Kilograms STANDARD_DEVIATION 4.55 | 63.1 Kilograms STANDARD_DEVIATION 16.14 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 6 | 2 / 3 | 2 / 3 | 11 / 17 | 16 / 21 | 33 / 40 | 30 / 43 | 0 / 12 |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 3 / 3 | 17 / 17 | 21 / 21 | 40 / 40 | 42 / 43 | 12 / 12 |
| serious Total, serious adverse events | 1 / 6 | 1 / 3 | 2 / 3 | 8 / 17 | 4 / 21 | 14 / 40 | 18 / 43 | 3 / 12 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab
Dose-limiting toxicities are severe side effects related to study treatment that may cause dose interruptions, dose reductions, or withdrawal of treatment.
Time frame: Study Day 1-42, for Cohorts 1-4.
Population: Participants in Cohorts 1-4 are evaluable for DLT during the first 42 days of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab | 1 Participants |
| Cohort 2 | Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab | 0 Participants |
| Cohort 3 | Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab | 0 Participants |
| Cohort 4 | Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab | 0 Participants |
Secondary
Best Overall Response (irRECIST 1.1)
The participants best response to treatment during their study participation. Responses are categorized as CR, PR, stable disease (SD), progressive disease (PD) or not evaluated (NE)
Time frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Population: Analysis performed using Response Evaluable Population that includes participants with baseline tumor assessment and at least 1 post-baseline tumor assessment.. NSCLC and SCCHN cohorts were subdivided by prior exposure to a PD1 or PDL1 inhibitor for the evaluation of efficacy. .
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Best Overall Response (irRECIST 1.1) | PR | 0 Participants |
| Cohort 1 | Best Overall Response (irRECIST 1.1) | NE | 1 Participants |
| Cohort 1 | Best Overall Response (irRECIST 1.1) | CR | 0 Participants |
| Cohort 1 | Best Overall Response (irRECIST 1.1) | SD | 4 Participants |
| Cohort 1 | Best Overall Response (irRECIST 1.1) | PD | 1 Participants |
| Cohort 2 | Best Overall Response (irRECIST 1.1) | PD | 2 Participants |
| Cohort 2 | Best Overall Response (irRECIST 1.1) | PR | 1 Participants |
| Cohort 2 | Best Overall Response (irRECIST 1.1) | NE | 0 Participants |
| Cohort 2 | Best Overall Response (irRECIST 1.1) | CR | 0 Participants |
| Cohort 2 | Best Overall Response (irRECIST 1.1) | SD | 0 Participants |
| Cohort 3 | Best Overall Response (irRECIST 1.1) | PD | 0 Participants |
| Cohort 3 | Best Overall Response (irRECIST 1.1) | SD | 3 Participants |
| Cohort 3 | Best Overall Response (irRECIST 1.1) | NE | 0 Participants |
| Cohort 3 | Best Overall Response (irRECIST 1.1) | PR | 0 Participants |
| Cohort 3 | Best Overall Response (irRECIST 1.1) | CR | 0 Participants |
| Cohort 4 | Best Overall Response (irRECIST 1.1) | SD | 7 Participants |
| Cohort 4 | Best Overall Response (irRECIST 1.1) | NE | 0 Participants |
| Cohort 4 | Best Overall Response (irRECIST 1.1) | CR | 0 Participants |
| Cohort 4 | Best Overall Response (irRECIST 1.1) | PD | 7 Participants |
| Cohort 4 | Best Overall Response (irRECIST 1.1) | PR | 1 Participants |
| Urothelial Cancer Cohort | Best Overall Response (irRECIST 1.1) | PR | 1 Participants |
| Urothelial Cancer Cohort | Best Overall Response (irRECIST 1.1) | NE | 0 Participants |
| Urothelial Cancer Cohort | Best Overall Response (irRECIST 1.1) | PD | 8 Participants |
| Urothelial Cancer Cohort | Best Overall Response (irRECIST 1.1) | SD | 8 Participants |
| Urothelial Cancer Cohort | Best Overall Response (irRECIST 1.1) | CR | 0 Participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Best Overall Response (irRECIST 1.1) | SD | 10 Participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Best Overall Response (irRECIST 1.1) | NE | 0 Participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Best Overall Response (irRECIST 1.1) | PR | 5 Participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Best Overall Response (irRECIST 1.1) | CR | 0 Participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Best Overall Response (irRECIST 1.1) | PD | 0 Participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Best Overall Response (irRECIST 1.1) | PR | 1 Participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Best Overall Response (irRECIST 1.1) | NE | 0 Participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Best Overall Response (irRECIST 1.1) | SD | 11 Participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Best Overall Response (irRECIST 1.1) | PD | 7 Participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Best Overall Response (irRECIST 1.1) | CR | 0 Participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Best Overall Response (irRECIST 1.1) | PR | 4 Participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Best Overall Response (irRECIST 1.1) | CR | 1 Participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Best Overall Response (irRECIST 1.1) | SD | 5 Participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Best Overall Response (irRECIST 1.1) | PD | 6 Participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Best Overall Response (irRECIST 1.1) | NE | 0 Participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Best Overall Response (irRECIST 1.1) | PD | 9 Participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Best Overall Response (irRECIST 1.1) | SD | 10 Participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Best Overall Response (irRECIST 1.1) | CR | 0 Participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Best Overall Response (irRECIST 1.1) | NE | 0 Participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Best Overall Response (irRECIST 1.1) | PR | 0 Participants |
| Cohort 4 | Best Overall Response (irRECIST 1.1) | SD | 6 Participants |
| Cohort 4 | Best Overall Response (irRECIST 1.1) | PR | 3 Participants |
| Cohort 4 | Best Overall Response (irRECIST 1.1) | PD | 3 Participants |
| Cohort 4 | Best Overall Response (irRECIST 1.1) | NE | 0 Participants |
| Cohort 4 | Best Overall Response (irRECIST 1.1) | CR | 0 Participants |
Secondary
Best Overall Response (RECIST 1.1)
The participants best response to treatment during their study participation. Responses are categorized as CR, PR, stable disease (SD), progressive disease (PD) or not evaluated (NE)
Time frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Population: Analysis performed using Response Evaluable Population that includes participants with baseline tumor assessment and at least 1 post-baseline tumor assessment.. NSCLC and SCCHN cohorts were subdivided by prior exposure to a PD1 or PDL1 inhibitor for the evaluation of efficacy. .
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Best Overall Response (RECIST 1.1) | CR | 0 Participants |
| Cohort 1 | Best Overall Response (RECIST 1.1) | SD | 4 Participants |
| Cohort 1 | Best Overall Response (RECIST 1.1) | PR | 0 Participants |
| Cohort 1 | Best Overall Response (RECIST 1.1) | NE | 1 Participants |
| Cohort 1 | Best Overall Response (RECIST 1.1) | PD | 1 Participants |
| Cohort 2 | Best Overall Response (RECIST 1.1) | PD | 2 Participants |
| Cohort 2 | Best Overall Response (RECIST 1.1) | CR | 0 Participants |
| Cohort 2 | Best Overall Response (RECIST 1.1) | SD | 0 Participants |
| Cohort 2 | Best Overall Response (RECIST 1.1) | PR | 1 Participants |
| Cohort 2 | Best Overall Response (RECIST 1.1) | NE | 0 Participants |
| Cohort 3 | Best Overall Response (RECIST 1.1) | PD | 0 Participants |
| Cohort 3 | Best Overall Response (RECIST 1.1) | NE | 0 Participants |
| Cohort 3 | Best Overall Response (RECIST 1.1) | CR | 0 Participants |
| Cohort 3 | Best Overall Response (RECIST 1.1) | SD | 3 Participants |
| Cohort 3 | Best Overall Response (RECIST 1.1) | PR | 0 Participants |
| Cohort 4 | Best Overall Response (RECIST 1.1) | NE | 0 Participants |
| Cohort 4 | Best Overall Response (RECIST 1.1) | PD | 9 Participants |
| Cohort 4 | Best Overall Response (RECIST 1.1) | SD | 5 Participants |
| Cohort 4 | Best Overall Response (RECIST 1.1) | CR | 0 Participants |
| Cohort 4 | Best Overall Response (RECIST 1.1) | PR | 1 Participants |
| Urothelial Cancer Cohort | Best Overall Response (RECIST 1.1) | CR | 0 Participants |
| Urothelial Cancer Cohort | Best Overall Response (RECIST 1.1) | SD | 8 Participants |
| Urothelial Cancer Cohort | Best Overall Response (RECIST 1.1) | NE | 0 Participants |
| Urothelial Cancer Cohort | Best Overall Response (RECIST 1.1) | PR | 1 Participants |
| Urothelial Cancer Cohort | Best Overall Response (RECIST 1.1) | PD | 8 Participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Best Overall Response (RECIST 1.1) | PR | 5 Participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Best Overall Response (RECIST 1.1) | PD | 1 Participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Best Overall Response (RECIST 1.1) | CR | 0 Participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Best Overall Response (RECIST 1.1) | SD | 9 Participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Best Overall Response (RECIST 1.1) | NE | 0 Participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Best Overall Response (RECIST 1.1) | CR | 0 Participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Best Overall Response (RECIST 1.1) | SD | 9 Participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Best Overall Response (RECIST 1.1) | NE | 0 Participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Best Overall Response (RECIST 1.1) | PD | 8 Participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Best Overall Response (RECIST 1.1) | PR | 2 Participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Best Overall Response (RECIST 1.1) | PR | 4 Participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Best Overall Response (RECIST 1.1) | CR | 1 Participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Best Overall Response (RECIST 1.1) | SD | 4 Participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Best Overall Response (RECIST 1.1) | PD | 7 Participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Best Overall Response (RECIST 1.1) | NE | 0 Participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Best Overall Response (RECIST 1.1) | PD | 10 Participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Best Overall Response (RECIST 1.1) | PR | 0 Participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Best Overall Response (RECIST 1.1) | CR | 0 Participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Best Overall Response (RECIST 1.1) | SD | 9 Participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Best Overall Response (RECIST 1.1) | NE | 0 Participants |
| Cohort 4 | Best Overall Response (RECIST 1.1) | SD | 7 Participants |
| Cohort 4 | Best Overall Response (RECIST 1.1) | PD | 3 Participants |
| Cohort 4 | Best Overall Response (RECIST 1.1) | NE | 0 Participants |
| Cohort 4 | Best Overall Response (RECIST 1.1) | CR | 0 Participants |
| Cohort 4 | Best Overall Response (RECIST 1.1) | PR | 2 Participants |
Secondary
Mean Area Under the Concentration Time Curve (AUC) From Time 0 to Day 7 of Enoblituzumab
AUC is the total body exposure to enoblituzumab MGA271 is characterized by a biphasic concentration-time profile and PPK was used to estimate PK parameters at each dose level
Time frame: At baseline, 1, 4, 24, 72 hours, and Day 7.
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. PK parameters are analyzed by the dose received. Participants in Cohort 3 and the Expansion Cohorts were combined since all participants were dosed at 15 mg/kg.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Area Under the Concentration Time Curve (AUC) From Time 0 to Day 7 of Enoblituzumab | 1207 mcg/mL*day | Standard Deviation 363.3 |
| Cohort 2 | Mean Area Under the Concentration Time Curve (AUC) From Time 0 to Day 7 of Enoblituzumab | 4540 mcg/mL*day | Standard Deviation 2445 |
| Cohort 3 | Mean Area Under the Concentration Time Curve (AUC) From Time 0 to Day 7 of Enoblituzumab | 5175 mcg/mL*day | Standard Deviation 1820 |
| Cohort 4 | Mean Area Under the Concentration Time Curve (AUC) From Time 0 to Day 7 of Enoblituzumab | 5919 mcg/mL*day | Standard Deviation 2009 |
Secondary
Mean Clearance of Enoblituzumab
Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time.
Time frame: At baseline, 1, 4, 24, 72 hours, and Day 7.
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. PK parameters are analyzed by the dose received. Participants in Cohort 3 and the Expansion Cohorts were combined since all participants were dosed at 15 mg/kg.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Clearance of Enoblituzumab | 0.155 liters per day | Standard Deviation 0.032 |
| Cohort 2 | Mean Clearance of Enoblituzumab | 0.154 liters per day | Standard Deviation 0.076 |
| Cohort 3 | Mean Clearance of Enoblituzumab | 0.235 liters per day | Standard Deviation 0.079 |
| Cohort 4 | Mean Clearance of Enoblituzumab | 0.210 liters per day | Standard Deviation 0.108 |
Secondary
Mean Maximum Concentration of Enoblituzumab
The highest measured concentration of enoblizuzumab in the bloodstream.
Time frame: Baseline, 1, 4, 24, and 72 hours after the first dose.
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. PK parameters are analyzed by the dose received. Participants in Cohort 3 and the Expansion Cohorts were combined since all participants were dosed at 15 mg/kg.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Maximum Concentration of Enoblituzumab | 223.5 mcg/mL | Standard Deviation 62.8 |
| Cohort 2 | Mean Maximum Concentration of Enoblituzumab | 860.0 mcg/mL | Standard Deviation 434.1 |
| Cohort 3 | Mean Maximum Concentration of Enoblituzumab | 995.4 mcg/mL | Standard Deviation 294.4 |
| Cohort 4 | Mean Maximum Concentration of Enoblituzumab | 580.2 mcg/mL | Standard Deviation 133.1 |
Secondary
Mean Terminal Half-life of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab
Terminal half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium MGA271 is characterized by a biphasic concentration-time profile and PPK was used to estimate PK parameters at each dose level
Time frame: At baseline, 1, 4, 24, and 72 and Day 7.
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. PK parameters are analyzed by the dose received. Participants in Cohort 3 and the Expansion Cohorts were combined since all participants were dosed at 15 mg/kg.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Terminal Half-life of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab | 29.22 days | Standard Deviation 4.337 |
| Cohort 2 | Mean Terminal Half-life of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab | 23.27 days | Standard Deviation 8.001 |
| Cohort 3 | Mean Terminal Half-life of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab | 20.05 days | Standard Deviation 6.975 |
| Cohort 4 | Mean Terminal Half-life of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab | 26.63 days | Standard Deviation 11.43 |
Secondary
Mean Trough Concentration of Enoblituzumab
Trough concentration is the concentration measured before the a subsequent dose of enoblituzumab. MGA271 is characterized by a biphasic concentration-time profile and PPK was used to estimate PK parameters at each dose level
Time frame: At baseline, and Day 7.
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. PK parameters are analyzed by the dose received. Participants in Cohort 3 and the Expansion Cohorts were combined since all participants were dosed at 15 mg/kg.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Trough Concentration of Enoblituzumab | 146.2 mcg/mL | Standard Deviation 48.1 |
| Cohort 2 | Mean Trough Concentration of Enoblituzumab | 551.0 mcg/mL | Standard Deviation 323.7 |
| Cohort 3 | Mean Trough Concentration of Enoblituzumab | 607.3 mcg/mL | Standard Deviation 246.4 |
| Cohort 4 | Mean Trough Concentration of Enoblituzumab | 180.2 mcg/mL | Standard Deviation 88 |
Secondary
Mean Volume of Distribution at Steady State of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab
The volume of distribution is related to how much drug is distributed to body tissues, or remains in the bloodstream
Time frame: At baseline, 1, 4, 24, and 72 and Day 7.
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. PK parameters are analyzed by the dose received. Participants in Cohort 3 and the Expansion Cohorts were combined since all participants were dosed at 15 mg/kg.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Volume of Distribution at Steady State of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab | 6.053 liters | Standard Deviation 0.986 |
| Cohort 2 | Mean Volume of Distribution at Steady State of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab | 4.340 liters | Standard Deviation 0.466 |
| Cohort 3 | Mean Volume of Distribution at Steady State of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab | 5.814 liters | Standard Deviation 1.357 |
| Cohort 4 | Mean Volume of Distribution at Steady State of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab | 6.299 liters | Standard Deviation 1.009 |
Secondary
Median Overall Survival
The time from the first infusion of pembrolizumab or retifanlimab until death from any cause.
Time frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Population: OS was calculated using the safety population. NSCLC and SCCHN cohorts were subdivided by prior exposure to a PD1 or PDL1 inhibitor for the evaluation of efficacy only. Safety assessment was conducted regardless of prior exposure to a PD1 or PDL1 inhibitor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Median Overall Survival | 18.0 months |
| Cohort 2 | Median Overall Survival | 10.3 months |
| Cohort 3 | Median Overall Survival | 6.3 months |
| Cohort 4 | Median Overall Survival | 14.4 months |
| Urothelial Cancer Cohort | Median Overall Survival | 5.7 months |
| NSCLC Cohort: PD1/PDL1 Naïve | Median Overall Survival | 10.3 months |
| NSCLC Cohort: PD1/PDL1 Experienced | Median Overall Survival | 6.0 months |
| SCCHN Cohort: PD1/PDL1 Naïve | Median Overall Survival | 17.9 months |
| SCCHN Cohort: PD1/PDL1 Experienced | Median Overall Survival | 6.9 months |
| Cohort 4 | Median Overall Survival | NA months |
Secondary
Median PFS Using irRECIST 1.1 Criteria
The time from the first infusion of pembrolizumab or retifanlimab until documented disease progression or death from any cause.
Time frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Population: PFS was calculated using the safety population. NSCLC and SCCHN cohorts were subdivided by prior exposure to a PD1 or PDL1 inhibitor for the evaluation of efficacy only. Safety assessment was conducted regardless of prior exposure to a PD1 or PDL1 inhibitor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Median PFS Using irRECIST 1.1 Criteria | NA months |
| Cohort 2 | Median PFS Using irRECIST 1.1 Criteria | 1.4 months |
| Cohort 3 | Median PFS Using irRECIST 1.1 Criteria | 3.6 months |
| Cohort 4 | Median PFS Using irRECIST 1.1 Criteria | 2.0 months |
| Urothelial Cancer Cohort | Median PFS Using irRECIST 1.1 Criteria | 2.2 months |
| NSCLC Cohort: PD1/PDL1 Naïve | Median PFS Using irRECIST 1.1 Criteria | 5.1 months |
| NSCLC Cohort: PD1/PDL1 Experienced | Median PFS Using irRECIST 1.1 Criteria | 3.5 months |
| SCCHN Cohort: PD1/PDL1 Naïve | Median PFS Using irRECIST 1.1 Criteria | 3.5 months |
| SCCHN Cohort: PD1/PDL1 Experienced | Median PFS Using irRECIST 1.1 Criteria | 1.4 months |
| Cohort 4 | Median PFS Using irRECIST 1.1 Criteria | 4.8 months |
Secondary
Median Progression-free Survival (PFS) Using RECIST 1.1
The time from the first infusion of pembrolizumab or retifanlimab until documented disease progression or death from any cause.
Time frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Population: PFS was calculated using the safety population. NSCLC and SCCHN cohorts were subdivided by prior exposure to a PD1 or PDL1 inhibitor for the evaluation of efficacy only. Safety assessment was conducted regardless of prior exposure to a PD1 or PDL1 inhibitor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Median Progression-free Survival (PFS) Using RECIST 1.1 | NA months |
| Cohort 2 | Median Progression-free Survival (PFS) Using RECIST 1.1 | 1.4 months |
| Cohort 3 | Median Progression-free Survival (PFS) Using RECIST 1.1 | 3.6 months |
| Cohort 4 | Median Progression-free Survival (PFS) Using RECIST 1.1 | 2.0 months |
| Urothelial Cancer Cohort | Median Progression-free Survival (PFS) Using RECIST 1.1 | 2.2 months |
| NSCLC Cohort: PD1/PDL1 Naïve | Median Progression-free Survival (PFS) Using RECIST 1.1 | 5.1 months |
| NSCLC Cohort: PD1/PDL1 Experienced | Median Progression-free Survival (PFS) Using RECIST 1.1 | 3.5 months |
| SCCHN Cohort: PD1/PDL1 Naïve | Median Progression-free Survival (PFS) Using RECIST 1.1 | 3.5 months |
| SCCHN Cohort: PD1/PDL1 Experienced | Median Progression-free Survival (PFS) Using RECIST 1.1 | 1.4 months |
| Cohort 4 | Median Progression-free Survival (PFS) Using RECIST 1.1 | 4.8 months |
Secondary
Minimum and Maximum DoR Per RECIST 1.1
The duration of response displays the minimum and maximum range in months from the first documented CR or PR until disease progression or death, whichever is first.
Time frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Population: Analysis performed using Response Evaluable Population that includes participants with baseline tumor assessment and at least 1 post-baseline tumor assessment.. NSCLC and SCCHN cohorts were subdivided by prior exposure to a PD1 or PDL1 inhibitor for the evaluation of efficacy. .
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Minimum and Maximum DoR Per RECIST 1.1 | Minimum DoR | NA months |
| Cohort 1 | Minimum and Maximum DoR Per RECIST 1.1 | Maximum DoR | NA months |
| Cohort 2 | Minimum and Maximum DoR Per RECIST 1.1 | Minimum DoR | 25.95 months |
| Cohort 2 | Minimum and Maximum DoR Per RECIST 1.1 | Maximum DoR | 25.95 months |
| Cohort 3 | Minimum and Maximum DoR Per RECIST 1.1 | Minimum DoR | NA months |
| Cohort 3 | Minimum and Maximum DoR Per RECIST 1.1 | Maximum DoR | NA months |
| Cohort 4 | Minimum and Maximum DoR Per RECIST 1.1 | Minimum DoR | 6.14 months |
| Cohort 4 | Minimum and Maximum DoR Per RECIST 1.1 | Maximum DoR | 6.14 months |
| Urothelial Cancer Cohort | Minimum and Maximum DoR Per RECIST 1.1 | Maximum DoR | 25.89 months |
| Urothelial Cancer Cohort | Minimum and Maximum DoR Per RECIST 1.1 | Minimum DoR | 25.89 months |
| NSCLC Cohort: PD1/PDL1 Naïve | Minimum and Maximum DoR Per RECIST 1.1 | Maximum DoR | 32.00 months |
| NSCLC Cohort: PD1/PDL1 Naïve | Minimum and Maximum DoR Per RECIST 1.1 | Minimum DoR | 3.48 months |
| NSCLC Cohort: PD1/PDL1 Experienced | Minimum and Maximum DoR Per RECIST 1.1 | Maximum DoR | 4.44 months |
| NSCLC Cohort: PD1/PDL1 Experienced | Minimum and Maximum DoR Per RECIST 1.1 | Minimum DoR | 4.44 months |
| SCCHN Cohort: PD1/PDL1 Naïve | Minimum and Maximum DoR Per RECIST 1.1 | Minimum DoR | 4.17 months |
| SCCHN Cohort: PD1/PDL1 Naïve | Minimum and Maximum DoR Per RECIST 1.1 | Maximum DoR | 23.72 months |
| SCCHN Cohort: PD1/PDL1 Experienced | Minimum and Maximum DoR Per RECIST 1.1 | Minimum DoR | NA months |
| SCCHN Cohort: PD1/PDL1 Experienced | Minimum and Maximum DoR Per RECIST 1.1 | Maximum DoR | NA months |
| Cohort 4 | Minimum and Maximum DoR Per RECIST 1.1 | Minimum DoR | 3.45 months |
| Cohort 4 | Minimum and Maximum DoR Per RECIST 1.1 | Maximum DoR | 6.24 months |
Secondary
Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1
The duration of response displays the minimum and maximum range in months from the first documented CR or PR until disease progression or death, whichever is first.
Time frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average13 months.
Population: Analysis performed using Response Evaluable Population that includes participants with baseline tumor assessment and at least 1 post-baseline tumor assessment.. NSCLC and SCCHN cohorts were subdivided by prior exposure to a PD1 or PDL1 inhibitor for the evaluation of efficacy. .
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Minimum DoR | NA months |
| Cohort 1 | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Maximum DoR | NA months |
| Cohort 2 | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Minimum DoR | 25.95 months |
| Cohort 2 | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Maximum DoR | 25.95 months |
| Cohort 3 | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Minimum DoR | NA months |
| Cohort 3 | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Maximum DoR | NA months |
| Cohort 4 | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Minimum DoR | 6.14 months |
| Cohort 4 | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Maximum DoR | 6.14 months |
| Urothelial Cancer Cohort | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Maximum DoR | 25.89 months |
| Urothelial Cancer Cohort | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Minimum DoR | 28.89 months |
| NSCLC Cohort: PD1/PDL1 Naïve | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Maximum DoR | 32.00 months |
| NSCLC Cohort: PD1/PDL1 Naïve | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Minimum DoR | 3.48 months |
| NSCLC Cohort: PD1/PDL1 Experienced | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Maximum DoR | 4.44 months |
| NSCLC Cohort: PD1/PDL1 Experienced | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Minimum DoR | 4.44 months |
| SCCHN Cohort: PD1/PDL1 Naïve | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Minimum DoR | 4.17 months |
| SCCHN Cohort: PD1/PDL1 Naïve | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Maximum DoR | 23.72 months |
| SCCHN Cohort: PD1/PDL1 Experienced | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Minimum DoR | NA months |
| SCCHN Cohort: PD1/PDL1 Experienced | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Maximum DoR | NA months |
| Cohort 4 | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Minimum DoR | 3.45 months |
| Cohort 4 | Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1 | Maximum DoR | 6.24 months |
Secondary
Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA)
Time frame: Every 3 weeks throughout the study, average duration 13 months.
Population: All participants who received at least one dose of enoblituzumab and have at least one ADA sample sufficient for analysis. ADA samples are analyzed by the dose received. Participants in Cohort 3 and the Expansion Cohorts were combined since all participants were dosed at 15 mg/kg.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Not done at baseline and not done post-baseline | 0 Participants |
| Cohort 1 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and not done post-baseline | 0 Participants |
| Cohort 1 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and positive at least once post-baseline | 1 Participants |
| Cohort 1 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Not done at baseline and negative post-baseline | 1 Participants |
| Cohort 1 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and not done post-baseline | 0 Participants |
| Cohort 1 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and negative post-baseline | 0 Participants |
| Cohort 1 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and negative post-baseline | 3 Participants |
| Cohort 1 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and positive at least once post-baseline | 1 Participants |
| Cohort 2 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and negative post-baseline | 0 Participants |
| Cohort 2 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and positive at least once post-baseline | 0 Participants |
| Cohort 2 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Not done at baseline and negative post-baseline | 0 Participants |
| Cohort 2 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and not done post-baseline | 0 Participants |
| Cohort 2 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and not done post-baseline | 0 Participants |
| Cohort 2 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and negative post-baseline | 3 Participants |
| Cohort 2 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and positive at least once post-baseline | 0 Participants |
| Cohort 2 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Not done at baseline and not done post-baseline | 0 Participants |
| Cohort 3 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and positive at least once post-baseline | 1 Participants |
| Cohort 3 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and negative post-baseline | 99 Participants |
| Cohort 3 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and not done post-baseline | 7 Participants |
| Cohort 3 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and negative post-baseline | 7 Participants |
| Cohort 3 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and positive at least once post-baseline | 2 Participants |
| Cohort 3 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and not done post-baseline | 4 Participants |
| Cohort 3 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Not done at baseline and not done post-baseline | 2 Participants |
| Cohort 3 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Not done at baseline and negative post-baseline | 2 Participants |
| Cohort 4 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and negative post-baseline | 0 Participants |
| Cohort 4 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and not done post-baseline | 0 Participants |
| Cohort 4 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Not done at baseline and negative post-baseline | 1 Participants |
| Cohort 4 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Not done at baseline and not done post-baseline | 0 Participants |
| Cohort 4 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and positive at least once post-baseline | 1 Participants |
| Cohort 4 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and positive at least once post-baseline | 0 Participants |
| Cohort 4 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Negative at baseline and negative post-baseline | 10 Participants |
| Cohort 4 | Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA) | Positive at baseline and not done post-baseline | 0 Participants |
Secondary
Number of Participants That Develop Retifanlimab ADA
Time frame: Every 3 weeks throughout the study, average duration 13 months.
Population: All participants who received at least one dose of retifanlimab and have at least one ADA sample sufficient for analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants That Develop Retifanlimab ADA | Negative at baseline and negative post-baseline | 11 Participants |
| Cohort 1 | Number of Participants That Develop Retifanlimab ADA | Negative at baseline and positive at least once post-baseline | 0 Participants |
Secondary
Objective Response Rate
The number of participants with a complete response (CR) or partial response (PR) to enoblituzumab in combination with pembrolizumab or retifanlimab RECIST 1.1 criteria.
Time frame: Six weeks after the first dose, then every 9 weeks throughout study until discontinuation, average 13 months
Population: Analysis performed using Response Evaluable Population that includes participants with baseline tumor assessment and at least 1 post-baseline tumor assessment.. NSCLC and SCCHN cohorts were subdivided by prior exposure to a PD1 or PDL1 inhibitor for the evaluation of efficacy. .
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1 | Objective Response Rate | 0 percentage of participants |
| Cohort 2 | Objective Response Rate | 33.3 percentage of participants |
| Cohort 3 | Objective Response Rate | 0 percentage of participants |
| Cohort 4 | Objective Response Rate | 6.7 percentage of participants |
| Urothelial Cancer Cohort | Objective Response Rate | 5.9 percentage of participants |
| NSCLC Cohort: PD1/PDL1 Naïve | Objective Response Rate | 33.3 percentage of participants |
| NSCLC Cohort: PD1/PDL1 Experienced | Objective Response Rate | 10.5 percentage of participants |
| SCCHN Cohort: PD1/PDL1 Naïve | Objective Response Rate | 31.3 percentage of participants |
| SCCHN Cohort: PD1/PDL1 Experienced | Objective Response Rate | 0 percentage of participants |
| Cohort 4 | Objective Response Rate | 16.7 percentage of participants |
Secondary
ORR Using Immune-related (ir) RECIST Criteria
The number of participants with a complete response (CR) or partial response (PR) to enoblituzumab in combination with pembrolizumab or retifanlimab using irRECIST 1.1 criteria.
Time frame: Six weeks after the first dose, then every 9 weeks throughout study until discontinuation, average 13 months
Population: Analysis performed using Response Evaluable Population that includes participants with baseline tumor assessment and at least 1 post-baseline tumor assessment.. NSCLC and SCCHN cohorts were subdivided by prior exposure to a PD1 or PDL1 inhibitor for the evaluation of efficacy. .
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1 | ORR Using Immune-related (ir) RECIST Criteria | 0 percentage of participants |
| Cohort 2 | ORR Using Immune-related (ir) RECIST Criteria | 33.3 percentage of participants |
| Cohort 3 | ORR Using Immune-related (ir) RECIST Criteria | 0 percentage of participants |
| Cohort 4 | ORR Using Immune-related (ir) RECIST Criteria | 6.7 percentage of participants |
| Urothelial Cancer Cohort | ORR Using Immune-related (ir) RECIST Criteria | 5.9 percentage of participants |
| NSCLC Cohort: PD1/PDL1 Naïve | ORR Using Immune-related (ir) RECIST Criteria | 33.3 percentage of participants |
| NSCLC Cohort: PD1/PDL1 Experienced | ORR Using Immune-related (ir) RECIST Criteria | 5.3 percentage of participants |
| SCCHN Cohort: PD1/PDL1 Naïve | ORR Using Immune-related (ir) RECIST Criteria | 31.3 percentage of participants |
| SCCHN Cohort: PD1/PDL1 Experienced | ORR Using Immune-related (ir) RECIST Criteria | 0 percentage of participants |
| Cohort 4 | ORR Using Immune-related (ir) RECIST Criteria | 25.0 percentage of participants |