Advanced Solid Tumor, Metastatic Solid Tumor, Solid Tumor, Adult
Conditions
Keywords
etigilimab, nivolumab, anti-TIGIT antibody, MPH313, Opdivo, ACTIVATE
Brief summary
This is an open-label, phase 1b/2, multicenter study designed to evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of etigilimab in combination with nivolumab in participants with locally advanced or metastatic solid tumors. Participants will be assigned to receive etigilimab (every 2 weeks) in combination with nivolumab (240 milligrams \[mg\] every 2 weeks).
Detailed description
This is an open-label, phase 1b/2, multicenter study designed to evaluate the efficacy, safety, tolerability, PK, and pharmacodynamics of etigilimab in combination with nivolumab in participants with locally advanced or metastatic solid tumors. Participants will be assigned to receive etigilimab (every 2 weeks) in combination with nivolumab (240 mg every 2 weeks) and will continue until either unacceptable toxicity or disease progression. Participants may continue to receive treatment beyond documented Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) or disease progression. Participants who are both checkpoint inhibitor (CPI) naive as well as participants who have received or progressed following a CPI will be eligible and include the following tumor types: head and neck squamous cell carcinoma (HNSCC), cervical carcinoma, gastric or gastroesophageal carcinoma, endometrial carcinoma, tumor mutation burden high (TMB-H), select rare tumors and ovarian carcinoma.
Interventions
DRUGEtigilimab
IV infusion of IV etigilimab every 2 weeks
DRUGNivolumab
IV infusion of nivolumab every 2 weeks
Sponsors
ICON Clinical Research
Mereo BioPharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Basket study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological diagnosis of a relevant tumor type as per the study protocol and not candidates for curative surgery or radiation therapy * Available tumor tissue (archival or newly obtained core or excisional biopsy) * Adequate hematologic and end organ function as measured by laboratory screening panel in the 14 days prior to treatment * Life expectancy greater than 12 weeks. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * Adequate contraception for women of childbearing potential * Pre-specified wash-out of prior anti-PD1/PDL-1 therapy
Exclusion criteria
* Concurrent active malignancy * Major surgery within 4 weeks of treatment * Participants with active, known or suspected autoimmune diseases * Prior treatment with cluster of differentiation (CD) 137 agonists, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) antibodies * History of any Grade 3 or 4 immune-related adverse event (AE) toxicity from prior immunotherapy that resulted in treatment discontinuation * History of immune-related adverse events that lead to discontinuation of anti-PD-1 or PDL-1 therapy * Active infections of human immunodeficiency virus (HIV), hepatitis B, hepatitis C * Medical illness or abnormal laboratory finding that would, in the Study Investigator's judgement, increase the risk to the participant associated with participation in the study * Pregnancy in female participants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | From first dose of study drug until the date of first objective response (CR or PR) (maximum exposure: 638 days) | The ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1. CR: Disappearance of all target or non-target lesions and normalization of tumor marker level. Any pathological lymph node (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | From first dose of study drug until the date of first BOR (CR, PR, or SD) (maximum exposure: 638 days) | The DCR was defined as the percentage of participants who achieved CR, PR, and stable disease (SD). CR: Disappearance of all target or non-target lesions and normalization of tumor marker level. Any pathological lymph node (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits; and no new lesions. |
| Duration of Response (DoR) as Assessed Based on RECIST v1.1 | From first dose of study drug until the date of first overall response of PD or date of death due to underlying cancer (maximum exposure: 638 days) | The DoR was defined as the time, in days, from the first of the 2 assessments required for confirmed PR or CR to the time of the progressive disease (PD) or death due to underlying cancer. CR: Disappearance of all target or non-target lesions and normalization of tumor marker level. Any pathological lymph node (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of the existing non-target lesions. The appearance of one or more new lesions was also considered progression. |
| Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | From first dose of study drug until 100 days after the last dose of study drug or the initiation of any subsequent cancer treatment, whichever occurs first (maximum exposure: 638 days) | TEAEs were defined as adverse events (AEs) with an onset date on or after the date of first administration of study drug up to 100 days after the last dose of study drug and before starting any subsequent cancer treatment. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AESIs were defined as events (serious or non-serious) which were of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor might be appropriate. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. |
| Serum Concentrations of Etigilimab | Pre-infusion and 15 minutes post-infusion on Cycle 1 Day 1 and Cycle 4 Day 43 | — |
| Number of Participants With Anti-drug Antibodies (ADA) to Etigilimab | From first dose of study drug until 100 days after the last dose of study drug or the initiation of any subsequent cancer treatment, whichever occurs first (maximum exposure: 638 days) | — |
| Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | From first dose of study drug until the date of first overall response of PD or date of death due to underlying cancer (up to a maximum of 680 days) | The DoSD was defined as the time, in days, from the first date of treatment until the first date at which PD was experienced or the participant died due to underlying cancer. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of the existing non-target lesions. The appearance of one or more new lesions was also considered progression. |
Countries
United Kingdom, United States
Participant flow
Pre-assignment details
Cohort D (Recurrent advanced and/or metastatic gastric or gastroesophageal junction adenocarcinoma) did not enroll any participants due to closure of the cohort by the Sponsor.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive Participants with endometrial cancer CPI (PD-1/PD-L1) naive received etigilimab in combination with nivolumab every 2 weeks and continued treatment until protocol-defined discontinuation criteria were met. | 11 |
| Cohort B: Head and Neck Squamous Cell Carcinoma Participants with head and neck cell carcinoma received etigilimab in combination with nivolumab every 2 weeks and continued treatment until protocol-defined discontinuation criteria were met. | 1 |
| Cohort C: Cervical Carcinoma Participants with cervical carcinoma received etigilimab in combination with nivolumab every 2 weeks and continued treatment until protocol-defined discontinuation criteria were met. | 8 |
| Cohort E: TMB-H + MSS Solid Tumors Participants with TMB-H and MSS solid tumors received etigilimab in combination with nivolumab every 2 weeks and continued treatment until protocol-defined discontinuation criteria were met. | 9 |
| Cohort F: Rare Tumors (Sarcoma, Uveal Melanoma, Germ Cell) Participants with rare tumors (sarcoma, uveal melanoma, and germ cell) received etigilimab in combination with nivolumab every 2 weeks and continued treatment until protocol-defined discontinuation criteria were met. | 33 |
| Cohort G: Endometrial Cancer Post- CPI (PD-1/PD-L1 Treated) Participants with endometrial cancer (PD-1/PD-L1 treated) received etigilimab in combination with nivolumab every 2 weeks and continued treatment until protocol-defined discontinuation criteria were met. | 4 |
| Cohort H: Ovarian Cancer Participants with ovarian cancer received etigilimab in combination with nivolumab every 2 weeks and continued treatment until protocol-defined discontinuation criteria were met. | 10 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 1 | 2 | 5 | 14 | 2 | 5 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Progressive Disease | 1 | 0 | 0 | 1 | 4 | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Study Terminated by Sponsor | 6 | 0 | 5 | 3 | 10 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Cohort B: Head and Neck Squamous Cell Carcinoma | Cohort C: Cervical Carcinoma | Cohort E: TMB-H + MSS Solid Tumors | Cohort F: Rare Tumors (Sarcoma, Uveal Melanoma, Germ Cell) | Cohort G: Endometrial Cancer Post- CPI (PD-1/PD-L1 Treated) | Cohort H: Ovarian Cancer | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.7 years STANDARD_DEVIATION 10.2 | 69.0 years | 49.1 years STANDARD_DEVIATION 13.53 | 62.0 years STANDARD_DEVIATION 10.14 | 55.8 years STANDARD_DEVIATION 13.9 | 65.3 years STANDARD_DEVIATION 11.79 | 68.1 years STANDARD_DEVIATION 11.43 | 59.5 years STANDARD_DEVIATION 13.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 1 Participants | 8 Participants | 8 Participants | 30 Participants | 4 Participants | 10 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 10 Participants | 1 Participants | 8 Participants | 9 Participants | 31 Participants | 2 Participants | 8 Participants | 69 Participants |
| Sex: Female, Male Female | 11 Participants | 0 Participants | 8 Participants | 4 Participants | 10 Participants | 4 Participants | 10 Participants | 47 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 23 Participants | 0 Participants | 0 Participants | 29 Participants |
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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 11 | 1 / 1 | 2 / 8 | 5 / 9 | 14 / 33 | 2 / 4 | 5 / 10 |
| other Total, other adverse events | 11 / 11 | 1 / 1 | 8 / 8 | 8 / 9 | 33 / 33 | 4 / 4 | 9 / 10 |
| serious Total, serious adverse events | 2 / 11 | 0 / 1 | 2 / 8 | 5 / 9 | 8 / 33 | 2 / 4 | 3 / 10 |
Outcome results
Primary
Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1)
The ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1. CR: Disappearance of all target or non-target lesions and normalization of tumor marker level. Any pathological lymph node (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dose of study drug until the date of first objective response (CR or PR) (maximum exposure: 638 days)
Population: RE Analysis Set included all participants with measurable disease at baseline who received study drug and had at least 1 post-baseline response assessment or discontinued treatment due to disease progression (including death due to disease progression) within 16 weeks (+ a 2-week window) of the first dose of study drug. Per planned analysis, the efficacy data for Cohort F were collected and analyzed separately per tumor type.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 20.0 percentage of participants |
| Cohort B: Head and Neck Squamous Cell Carcinoma | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 0 percentage of participants |
| Cohort C: Cervical Carcinoma | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 37.5 percentage of participants |
| Cohort E: TMB-H + MSS Solid Tumors | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 0 percentage of participants |
| Cohort F: Rare Tumors (Uveal) | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 25.0 percentage of participants |
| Cohort F: Rare Tumors (De-diff LPS) | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 10.0 percentage of participants |
| Cohort F: Rare Tumors (UPS) | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 16.7 percentage of participants |
| Cohort F: Rare Tumors (Other Sarcoma) | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 0 percentage of participants |
| Cohort F: Rare Tumors (GCT) | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 0 percentage of participants |
| Cohort G: Endometrial Cancer Post- CPI (PD-1/PD-L1 Treated) | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 0 percentage of participants |
| Cohort H: Ovarian Cancer | Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) | 10.0 percentage of participants |
Secondary
Disease Control Rate (DCR) as Assessed Based on RECIST v1.1
The DCR was defined as the percentage of participants who achieved CR, PR, and stable disease (SD). CR: Disappearance of all target or non-target lesions and normalization of tumor marker level. Any pathological lymph node (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits; and no new lesions.
Time frame: From first dose of study drug until the date of first BOR (CR, PR, or SD) (maximum exposure: 638 days)
Population: RE Analysis Set included all participants with measurable disease at baseline who received study drug and had at least 1 post-baseline response assessment or discontinued treatment due to disease progression (including death due to disease progression) within 16 weeks (+ a 2-week window) of the first dose of study drug. Per planned analysis, the efficacy data for Cohort F were collected and analyzed separately per tumor type.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 50.0 percentage of participants |
| Cohort B: Head and Neck Squamous Cell Carcinoma | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 0 percentage of participants |
| Cohort C: Cervical Carcinoma | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 62.5 percentage of participants |
| Cohort E: TMB-H + MSS Solid Tumors | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 33.3 percentage of participants |
| Cohort F: Rare Tumors (Uveal) | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 50.0 percentage of participants |
| Cohort F: Rare Tumors (De-diff LPS) | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 50.0 percentage of participants |
| Cohort F: Rare Tumors (UPS) | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 33.3 percentage of participants |
| Cohort F: Rare Tumors (Other Sarcoma) | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 33.3 percentage of participants |
| Cohort F: Rare Tumors (GCT) | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 0 percentage of participants |
| Cohort G: Endometrial Cancer Post- CPI (PD-1/PD-L1 Treated) | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 0 percentage of participants |
| Cohort H: Ovarian Cancer | Disease Control Rate (DCR) as Assessed Based on RECIST v1.1 | 60.0 percentage of participants |
Secondary
Duration of Response (DoR) as Assessed Based on RECIST v1.1
The DoR was defined as the time, in days, from the first of the 2 assessments required for confirmed PR or CR to the time of the progressive disease (PD) or death due to underlying cancer. CR: Disappearance of all target or non-target lesions and normalization of tumor marker level. Any pathological lymph node (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of the existing non-target lesions. The appearance of one or more new lesions was also considered progression.
Time frame: From first dose of study drug until the date of first overall response of PD or date of death due to underlying cancer (maximum exposure: 638 days)
Population: RE Analysis Set: all participants with measurable disease at baseline who received study drug and had at least 1 post-baseline response assessment or discontinued treatment due to disease progression (including death due to disease progression) within 16 weeks of first dose of study drug. Per planned analysis, the efficacy data for Cohort F were collected and analyzed separately per tumor type. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Duration of Response (DoR) as Assessed Based on RECIST v1.1 | 197.0 days |
| Cohort C: Cervical Carcinoma | Duration of Response (DoR) as Assessed Based on RECIST v1.1 | 183.0 days |
| Cohort F: Rare Tumors (Uveal) | Duration of Response (DoR) as Assessed Based on RECIST v1.1 | 307.0 days |
| Cohort F: Rare Tumors (De-diff LPS) | Duration of Response (DoR) as Assessed Based on RECIST v1.1 | 464.0 days |
| Cohort F: Rare Tumors (UPS) | Duration of Response (DoR) as Assessed Based on RECIST v1.1 | 145.0 days |
| Cohort H: Ovarian Cancer | Duration of Response (DoR) as Assessed Based on RECIST v1.1 | 442.0 days |
Secondary
Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1
The DoSD was defined as the time, in days, from the first date of treatment until the first date at which PD was experienced or the participant died due to underlying cancer. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of the existing non-target lesions. The appearance of one or more new lesions was also considered progression.
Time frame: From first dose of study drug until the date of first overall response of PD or date of death due to underlying cancer (up to a maximum of 680 days)
Population: RE Analysis Set included all participants with measurable disease at baseline who received study drug and had at least 1 post-baseline response assessment or discontinued treatment due to disease progression (including death due to disease progression) within 16 weeks (+ a 2-week window) of the first dose of study drug. Per planned analysis, the efficacy data for Cohort F were collected and analyzed separately per tumor type.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 81.5 days |
| Cohort B: Head and Neck Squamous Cell Carcinoma | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 45.0 days |
| Cohort C: Cervical Carcinoma | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 120.0 days |
| Cohort E: TMB-H + MSS Solid Tumors | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 57.0 days |
| Cohort F: Rare Tumors (Uveal) | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 109.5 days |
| Cohort F: Rare Tumors (De-diff LPS) | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 108.0 days |
| Cohort F: Rare Tumors (UPS) | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 55.5 days |
| Cohort F: Rare Tumors (Other Sarcoma) | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 53.0 days |
| Cohort F: Rare Tumors (GCT) | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 57.5 days |
| Cohort G: Endometrial Cancer Post- CPI (PD-1/PD-L1 Treated) | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 50.0 days |
| Cohort H: Ovarian Cancer | Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1 | 70.0 days |
Secondary
Number of Participants With Anti-drug Antibodies (ADA) to Etigilimab
Time frame: From first dose of study drug until 100 days after the last dose of study drug or the initiation of any subsequent cancer treatment, whichever occurs first (maximum exposure: 638 days)
Population: The immunogenicity analysis set included all participants with at least 1 evaluable post-treatment immunogenicity sample.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort B: Head and Neck Squamous Cell Carcinoma | Number of Participants With Anti-drug Antibodies (ADA) to Etigilimab | 0 Participants |
| Cohort C: Cervical Carcinoma | Number of Participants With Anti-drug Antibodies (ADA) to Etigilimab | 0 Participants |
| Cohort F: Rare Tumors (Uveal) | Number of Participants With Anti-drug Antibodies (ADA) to Etigilimab | 0 Participants |
| Cohort F: Rare Tumors (UPS) | Number of Participants With Anti-drug Antibodies (ADA) to Etigilimab | 0 Participants |
Secondary
Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions
TEAEs were defined as adverse events (AEs) with an onset date on or after the date of first administration of study drug up to 100 days after the last dose of study drug and before starting any subsequent cancer treatment. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AESIs were defined as events (serious or non-serious) which were of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor might be appropriate. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Time frame: From first dose of study drug until 100 days after the last dose of study drug or the initiation of any subsequent cancer treatment, whichever occurs first (maximum exposure: 638 days)
Population: Safety Analysis Set included all participants who received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any TEAEs | 11 Participants |
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any AESIs | 4 Participants |
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Immune Related AEs | 2 Participants |
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Infusion Reactions | 2 Participants |
| Cohort B: Head and Neck Squamous Cell Carcinoma | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Infusion Reactions | 0 Participants |
| Cohort B: Head and Neck Squamous Cell Carcinoma | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Immune Related AEs | 0 Participants |
| Cohort B: Head and Neck Squamous Cell Carcinoma | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any TEAEs | 1 Participants |
| Cohort B: Head and Neck Squamous Cell Carcinoma | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any AESIs | 0 Participants |
| Cohort C: Cervical Carcinoma | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Immune Related AEs | 2 Participants |
| Cohort C: Cervical Carcinoma | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any AESIs | 3 Participants |
| Cohort C: Cervical Carcinoma | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any TEAEs | 8 Participants |
| Cohort C: Cervical Carcinoma | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Infusion Reactions | 1 Participants |
| Cohort E: TMB-H + MSS Solid Tumors | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any TEAEs | 8 Participants |
| Cohort E: TMB-H + MSS Solid Tumors | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any AESIs | 0 Participants |
| Cohort E: TMB-H + MSS Solid Tumors | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Immune Related AEs | 0 Participants |
| Cohort E: TMB-H + MSS Solid Tumors | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Infusion Reactions | 0 Participants |
| Cohort F: Rare Tumors (Uveal) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any TEAEs | 33 Participants |
| Cohort F: Rare Tumors (Uveal) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Infusion Reactions | 2 Participants |
| Cohort F: Rare Tumors (Uveal) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any AESIs | 5 Participants |
| Cohort F: Rare Tumors (Uveal) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Immune Related AEs | 3 Participants |
| Cohort F: Rare Tumors (De-diff LPS) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any AESIs | 0 Participants |
| Cohort F: Rare Tumors (De-diff LPS) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any TEAEs | 4 Participants |
| Cohort F: Rare Tumors (De-diff LPS) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Immune Related AEs | 0 Participants |
| Cohort F: Rare Tumors (De-diff LPS) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Infusion Reactions | 0 Participants |
| Cohort F: Rare Tumors (UPS) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Immune Related AEs | 1 Participants |
| Cohort F: Rare Tumors (UPS) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any TEAEs | 9 Participants |
| Cohort F: Rare Tumors (UPS) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | Any AESIs | 1 Participants |
| Cohort F: Rare Tumors (UPS) | Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions | AESI Infusion Reactions | 0 Participants |
Secondary
Serum Concentrations of Etigilimab
Time frame: Pre-infusion and 15 minutes post-infusion on Cycle 1 Day 1 and Cycle 4 Day 43
Population: The pharmacokinetic (PK) analysis set included all participants with sufficient plasma concentration data to allow the characterization of the PK parameters. Per planned analysis, PK data were collected and analyzed combined for all arm groups. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Serum Concentrations of Etigilimab | Cycle 1 Day 1 (Pre-infusion) | NA micrograms (μg)/milliliter (mL) | — |
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Serum Concentrations of Etigilimab | Cycle 1 Day 1 (15 minutes post-infusion) | 262 micrograms (μg)/milliliter (mL) | Geometric Coefficient of Variation 22 |
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Serum Concentrations of Etigilimab | Cycle 4 Day 43 (Pre-infusion) | 20.1 micrograms (μg)/milliliter (mL) | Geometric Coefficient of Variation 82 |
| Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive | Serum Concentrations of Etigilimab | Cycle 4 Day 43 (15 minutes post-infusion) | 273 micrograms (μg)/milliliter (mL) | Geometric Coefficient of Variation 27 |