Pharmacokinetics, Solid Tumor, Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms
Conditions
Keywords
Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), Programmed Cell Death Receptor Ligand 2 (PD-L2), PD-1, PDL1, PD-L1, PD-L2
Brief summary
The purpose of this study is to assess the safety and pharmacokinetics of boserolimab (MK-5890) when administered alone and in combination with pembrolizumab (MK-3475) in adults. Boserolimab monotherapy or boserolimab plus pembrolizumab combination therapy will be administered in adults with advanced solid tumors, including endometrial cancer, for up to 35 administrations (approximately 2 years). The safety and pharmacokinetics of boserolimab when administered with pembrolizumab, pemetrexed and carboplatin in adults with non-squamous non-small cell lung cancer (NSCLC) and boserolimab when administered with pembrolizumab and nab-paclitaxel in adults with triple-negative breast cancer (TNBC) will also be assessed.
Detailed description
Participants receiving boserolimab monotherapy who experience disease progression may be eligible to switch to receiving boserolimab plus pembrolizumab combination therapy at an eligible dose for up to 35 cycles (approximately 2 years) at the discretion of the Investigator and approval of the Sponsor. Per protocol, pharmacokinetic (PK) outcome measures will not be analyzed separately for the switch-over treatment arms.
Interventions
DRUGBoserolimab
IV infusion
BIOLOGICALPembrolizumab
IV infusion
DRUGPemetrexed
IV infusion
DRUGCarboplatin
IV infusion
DRUGNab-paclitaxel
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Arms 1 & 2: Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and has received or been intolerant to all treatment known to confer clinical benefit * Arm 3: Histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b per current American Joint Committee on Cancer criteria) non-squamous NSCLC * Arm 4: Triple-negative breast cancer (TNBC) that is locally recurrent, inoperable, not previously treated with chemotherapy, and which cannot be treated with curative intent OR metastatic disease not previously treated with chemotherapy * Measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiologist. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions * Adequate organ function * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Male participants must agree to use adequate contraception during the treatment period and for at least 120 days after the last dose of boserolimab or pembrolizumab OR 180 days after the last dose of chemotherapeutic agents and refrain from donating sperm during this period * Female participants must not be pregnant or breastfeeding and agree to follow use adequate contraception during the treatment period and for at least 120 days after the last dose of boserolimab or pembrolizumab OR 180 days after the last dose of chemotherapeutic agents * Submit an evaluable baseline tumor sample for analysis (either a newly obtained or archival tumor sample)
Exclusion criteria
* History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years * Clinically active central nervous system metastases and/or carcinomatous meningitis * Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAb) and/or other components of the study treatment * Active infection requiring systemic treatment * History of interstitial lung disease * History of (noninfectious) pneumonitis that required steroids or current pneumonitis * Symptomatic ascites or pleural effusion * Previously had a stem cell or bone marrow transplant * Previously had a solid organ transplant * Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy * Known human immunodeficiency virus (HIV) and/or active and acute Hepatitis B or C infections * Not fully recovered from any effects of major surgery without significant detectable infection * Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study * Had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study treatment, or has not recovered to Grade ≤1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier * Expected to require any other form of antineoplastic therapy while participating in this study * On chronic systemic steroid therapy in excess of replacement doses (e.g., exceeding 10 mg/day of prednisone equivalent), or on any other form of immunosuppressive medication * Regular user (including recreational use) of any illicit drugs at the time of signing informed consent, or has a recent history (within the last year) of substance abuse (including alcohol), as determined by the treating investigator. Participants who use cannabis for medicinal purposes or to treat specific symptoms will not be excluded unless it is being abused in the opinion of the treating investigator * Received a live-virus vaccine within 28 days before the first dose of study treatment * Currently participating and receiving study treatment in a study of an investigational agent or has participated and received study treatment in a study of an investigational agent or has used an investigational device within 28 days before the first dose of study treatment Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | Up to 21 days in Cycle 1 | DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. A DLT was defined as any of the following events: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia requiring a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality; Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study drug discontinuation during the DLT evaluation period; Missing \>25% of any study drug during the DLT evaluation period due to a treatment-related AE; or Grade 5 toxicity. The number of participants who experienced one or more DLTs is reported. |
| Number of Participants With One or More AEs | Up to approximately 78 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced one or more AEs is reported. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to 23 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study treatment due to an AE is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Concentration (Cmin) of Boserolimab | Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2 | Cmin of boserolimab was defined as the minimum concentration of boserolimab observed in serum. Samples were taken predose and at specified times postdose to determine the Cmin of boserolimab. PK collection time frames include: Arms 1, 2 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 5, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 1a, 2a, 2b, 3 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1, and predose on Day 1 of Cycle 2. |
| Maximum Concentration (Cmax) of Boserolimab | Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2 | Cmax of boserolimab was defined as the maximum concentration of boserolimab observed in serum. Samples were taken predose and at specified times postdose to determine the Cmax of boserolimab. PK collection time frames include: Arms 1, 2 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 5, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 1a, 2a, 2b, 3 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1, and predose on Day 1 of Cycle 2. |
| Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Up to approximately 78 months | ORR was defined as the percentage of participants who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. As pre-specified in the protocol, ORR was analyzed for participants treated with boserolimab when used as monotherapy in Arm 1a, in combination with pembrolizumab in Switch-over Arm 1a and Arms 2a, 2b, and 2c, or in combination with pembrolizumab + nab-paclitaxel in Arm 4. Per protocol, ORR was not analyzed in Arms 1, 2, or 3. The percentage of participants who experienced a CR or PR, as assessed by the investigator, is reported. |
| Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2 | AUC0-last was defined as the area under the concentration versus time curve for boserolimab from 0 to the time of the last quantifiable concentration in serum. Samples were taken predose and at specified times postdose to determine the AUC0-last of boserolimab. PK collection time frames include: Arms 1, 2 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 5, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 1a, 2a, 2b, 3 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1, and predose on Day 1 of Cycle 2. |
| Arm 4: Number of Participants Who Experienced a DLT | Up to 28 days in Cycle 1 | DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. A DLT was defined as any of the following events: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia requiring a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality; Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study drug discontinuation during the DLT evaluation period; Missing \>25% of any study drug during the DLT evaluation period due to a treatment-related AE; or Grade 5 toxicity. The number of participants who experienced one or more DLTs in Arm 4 is reported. |
| Arm 3 and 4: Number of Participants With One or More AEs | Up to 57 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Arms 3 and 4 who experienced one or more AEs is reported. |
| Arm 3 and 4: Number of Participants Who Discontinued Study Treatment Due to an AE | Up to 27 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Arms 3 or 4 who discontinued study treatment due to an AE is reported. |
| Arm 3: Number of Participants Who Experienced a DLT | Up to 21 days in Cycle 1 | DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. A DLT was defined as any of the following events: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia requiring a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality; Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study drug discontinuation during the DLT evaluation period; Missing \>25% of any study drug during the DLT evaluation period due to a treatment-related AE; or Grade 5 toxicity. The number of participants who experienced one or more DLTs in Arm 3 is reported |
| Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2 | AUC0-3w was defined as the area under the concentration versus time curve for boserolimab from 0 to 3 weeks in serum. Samples were taken predose and at specified times postdose to determine the AUC0-3w of boserolimab. PK collection time frames include: Arms 1, 2 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 5, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 1a, 2a, 2b, 3 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1. |
| Area Under the Concentration-Time Curve From Time 0 to 6 Weeks (AUC0-6w) of Boserolimab | Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1, and predose on Day 1 Cycle 2 | AUC0-6w was defined as the area under the concentration versus time curve for boserolimab from 0 to 6 weeks in serum. Samples were taken predose and at specified times postdose to determine the AUC0-6w of boserolimab. As pre-specified in the protocol, different arms had different sampling schedules and cycle lengths and therefore AUC0-6w was not analyzed for all Arms; AUC0-6w was only analyzed for Arms 2c and 4 which had 6-week cycles. |
Countries
Chile, Israel, Netherlands, South Korea, Spain, Taiwan, United States
Participant flow
Pre-assignment details
Per protocol, pharmacokinetic (PK) outcome measures were not analyzed separately for the switch-over treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Boserolimab 2 mg Q3W Participants received boserolimab 2 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 3 |
| Arm 1 Boserolimab 7 mg Q3W Participants received boserolimab 7 mg via intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long | 3 |
| Arm 1 Boserolimab 20 mg Q3W Participants received boserolimab 20 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 6 |
| Arm 1 Boserolimab 70 mg Q3W Participants received boserolimab 70 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 3 |
| Arm 1 Boserolimab 200 mg Q3W Participants received boserolimab 200 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 9 |
| Arm 1 Boserolimab 700 mg Q3W Participants received boserolimab 700 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 2 |
| Arm 1a Boserolimab 30 mg Q3W (Endometrial) Participants with endometrial cancer received boserolimab 30 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 14 |
| Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W Participants received separate IV infusions of boserolimab 2 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab were administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 3 |
| Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W Participants received separate IV infusions of boserolimab 7 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab were administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 3 |
| Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W Participants received separate IV infusions of boserolimab 20 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab were administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 4 |
| Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W Participants received separate IV infusions of boserolimab 70 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab were administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 7 |
| Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W Participants received separate IV infusions of boserolimab 200 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab were administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 14 |
| Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC) Participants with triple-negative breast cancer (TNBC) received separate IV infusions of boserolimab 30 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab were administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 31 |
| Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial) Participants with endometrial cancer received separate IV infusions of boserolimab 30 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab were administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle was 3 weeks long. | 15 |
| Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial) Participants with endometrial cancer received separate IV infusions of boserolimab 30 mg and pembrolizumab 400 mg. Boserolimab was administered once Q6W on Day 1 of each cycle for a total of up to approximately 4 cycles (up to approximately 6 months). Pembrolizumab was administered once Q6W on Day 1 of each cycle for a total of up to approximately 18 cycles (up to approximately 27 months). Each cycle was 6 weeks long. | 14 |
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) Participants with non-small cell lung cancer (NSCLC) received separate IV infusions of boserolimab 30 mg, pembrolizumab 200 mg, pemetrexed 500 mg/m\^2, and carboplatin area under the curve (AUC) 5 mg/mL/min. Boserolimab was administered once Q3W on Day 1 of each cycle for a total of up to approximately 8 cycles (up to approximately 6 months). Pembrolizumab and pemetrexed were administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Carboplatin was administered once Q3W on Day 1 of each cycle for a total of up to approximately 4 cycles (up to approximately 3 months). Each cycle was 3 weeks long. | 10 |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) Participants with TNBC received separate IV infusions of boserolimab 30 mg, pembrolizumab 400 mg, and nab-paclitaxel 100 mg/m\^2. Boserolimab and pembrolizumab were administered once Q6W on Day 1 of each cycle for a total of up to approximately 18 cycles (up to approximately 27 months). Nab-paclitaxel was administered on a 3-weeks on/1-week off schedule every 28 days (Days 1, 8, 15, 29, and 36 of odd-numbered cycles and Days 1, 15, 22, and 29 of even-numbered cycles). Each cycle was 6 weeks long. | 41 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 | FG025 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Switch-over Period | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 2 | 1 | 2 | 0 | 1 | 6 |
| Switch-over Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Treatment Period | Death | 2 | 2 | 1 | 1 | 3 | 2 | 5 | 3 | 3 | 3 | 7 | 12 | 28 | 14 | 10 | 8 | 18 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Progressive Disease, Switched Over to Boserolimab + Pembrolizumab Combination Treatment | 1 | 1 | 5 | 2 | 5 | 0 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Randomized by Mistake without Study Treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 1 Boserolimab 2 mg Q3W | Arm 1 Boserolimab 7 mg Q3W | Arm 1 Boserolimab 20 mg Q3W | Arm 1 Boserolimab 70 mg Q3W | Arm 1 Boserolimab 200 mg Q3W | Arm 1 Boserolimab 700 mg Q3W | Arm 1a Boserolimab 30 mg Q3W (Endometrial) | Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W | Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W | Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W | Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W | Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W | Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC) | Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial) | Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial) | Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 55.3 Years STANDARD_DEVIATION 18.9 | 57.3 Years STANDARD_DEVIATION 18 | 57.0 Years STANDARD_DEVIATION 15.8 | 54.0 Years STANDARD_DEVIATION 15.7 | 61.6 Years STANDARD_DEVIATION 14.2 | 61.0 Years STANDARD_DEVIATION 2.8 | 71.6 Years STANDARD_DEVIATION 5.7 | 44.7 Years STANDARD_DEVIATION 15.6 | 50.0 Years STANDARD_DEVIATION 24.3 | 61.5 Years STANDARD_DEVIATION 6.2 | 59.9 Years STANDARD_DEVIATION 7.2 | 55.1 Years STANDARD_DEVIATION 16.1 | 50.4 Years STANDARD_DEVIATION 13.3 | 64.6 Years STANDARD_DEVIATION 7.1 | 68.5 Years STANDARD_DEVIATION 9.5 | 61.9 Years STANDARD_DEVIATION 9.4 | 51.7 Years STANDARD_DEVIATION 11.8 | 57.5 Years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 11 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants | 3 Participants | 5 Participants | 2 Participants | 14 Participants | 3 Participants | 3 Participants | 4 Participants | 6 Participants | 14 Participants | 26 Participants | 14 Participants | 13 Participants | 9 Participants | 30 Participants | 158 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 10 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 | 00 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 15 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 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 | 0 Participants | 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 | 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 | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 6 Participants | 3 Participants | 6 Participants | 2 Participants | 13 Participants | 3 Participants | 3 Participants | 4 Participants | 7 Participants | 13 Participants | 30 Participants | 13 Participants | 14 Participants | 10 Participants | 26 Participants | 159 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 14 Participants | 2 Participants | 0 Participants | 1 Participants | 7 Participants | 10 Participants | 31 Participants | 15 Participants | 14 Participants | 6 Participants | 41 Participants | 155 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 4 Participants | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 27 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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 2 / 3 | 1 / 6 | 1 / 3 | 3 / 9 | 2 / 2 | 5 / 14 | 3 / 3 | 3 / 3 | 4 / 4 | 7 / 7 | 12 / 14 | 29 / 31 | 14 / 15 | 10 / 14 | 8 / 10 | 18 / 41 | 0 / 1 | 1 / 1 | 2 / 2 | 2 / 3 | 1 / 2 | 2 / 2 | 0 / 2 | 1 / 1 | 6 / 9 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 3 / 3 | 8 / 8 | 2 / 2 | 14 / 14 | 3 / 3 | 3 / 3 | 3 / 3 | 7 / 7 | 14 / 14 | 30 / 30 | 15 / 15 | 13 / 13 | 10 / 10 | 40 / 41 | 1 / 1 | 1 / 1 | 2 / 2 | 3 / 3 | 2 / 2 | 2 / 2 | 2 / 2 | 1 / 1 | 8 / 9 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 0 / 6 | 0 / 3 | 1 / 8 | 1 / 2 | 2 / 14 | 1 / 3 | 0 / 3 | 1 / 3 | 1 / 7 | 3 / 14 | 11 / 30 | 2 / 15 | 0 / 13 | 9 / 10 | 13 / 41 | 0 / 1 | 0 / 1 | 1 / 2 | 1 / 3 | 0 / 2 | 2 / 2 | 0 / 2 | 0 / 1 | 3 / 9 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study treatment due to an AE is reported.
Time frame: Up to 23 months
Population: All participants in Arms 1, 1a, 2, 2a, 2b, 2c, and Switch-over Arms who received ≥1 dose of study treatment. As pre-specified in the protocol, safety data were analyzed separately for the Switch-over Arms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Arm 1 Boserolimab 20 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Arm 1 Boserolimab 70 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Arm 1 Boserolimab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Arm 1 Boserolimab 700 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| Arm 1a Boserolimab 30 mg Q3W (Endometrial) | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC) | Number of Participants Who Discontinued Study Treatment Due to an AE | 4 Participants |
| Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial) | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial) | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 Boserolimab 20 mg Q3W To Boserolimab 7 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 Boserolimab 20 mg Q3W To Boserolimab 20 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Switch-over Arm 1 Boserolimab 70 mg Q3W To Boserolimab 20 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 Boserolimab 200 mg Q3W To Boserolimab 20 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 Boserolimab 200 mg Q3W To Boserolimab 70 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 Boserolimab 200 mg Q3W To Boserolimab 200 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1a Boserolimab 30mg Q3W (Endometrial) To Boserolimab 30mg + Pembrolizumab 200mg Q3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
Primary
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. A DLT was defined as any of the following events: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia requiring a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality; Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study drug discontinuation during the DLT evaluation period; Missing \>25% of any study drug during the DLT evaluation period due to a treatment-related AE; or Grade 5 toxicity. The number of participants who experienced one or more DLTs is reported.
Time frame: Up to 21 days in Cycle 1
Population: All participants in Arms 1, 1a, 2, 2a, 2b, 2c, and Switch-over Arms who received ≥1 dose of study treatment and who were observed for DLTs for up to 21 days following the first dose of study treatment in Cycle 1. As pre-specified in the protocol, DLTs were analyzed separately for the Switch-over Arms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 1 Boserolimab 20 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
| Arm 1 Boserolimab 70 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 1 Boserolimab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 1 Boserolimab 700 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 2 Participants |
| Arm 1a Boserolimab 30 mg Q3W (Endometrial) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
| Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Switch-over Arm 1 Boserolimab 20 mg Q3W To Boserolimab 7 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Switch-over Arm 1 Boserolimab 20 mg Q3W To Boserolimab 20 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Switch-over Arm 1 Boserolimab 70 mg Q3W To Boserolimab 20 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Switch-over Arm 1 Boserolimab 200 mg Q3W To Boserolimab 20 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Switch-over Arm 1 Boserolimab 200 mg Q3W To Boserolimab 70 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Switch-over Arm 1 Boserolimab 200 mg Q3W To Boserolimab 200 mg + Pembrolizumab 200 mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Switch-over Arm 1a Boserolimab 30mg Q3W (Endometrial) To Boserolimab 30mg + Pembrolizumab 200mg Q3W | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
Primary
Number of Participants With One or More AEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced one or more AEs is reported.
Time frame: Up to approximately 78 months
Population: All participants in Arms 1, 1a, 2, 2a, 2b, 2c, and Switch-over Arms who received ≥1 dose of study treatment. As pre-specified in the protocol, safety data were analyzed separately for the Switch-over Arms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Number of Participants With One or More AEs | 3 Participants |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Number of Participants With One or More AEs | 3 Participants |
| Arm 1 Boserolimab 20 mg Q3W | Number of Participants With One or More AEs | 6 Participants |
| Arm 1 Boserolimab 70 mg Q3W | Number of Participants With One or More AEs | 3 Participants |
| Arm 1 Boserolimab 200 mg Q3W | Number of Participants With One or More AEs | 8 Participants |
| Arm 1 Boserolimab 700 mg Q3W | Number of Participants With One or More AEs | 2 Participants |
| Arm 1a Boserolimab 30 mg Q3W (Endometrial) | Number of Participants With One or More AEs | 14 Participants |
| Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 3 Participants |
| Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 3 Participants |
| Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 3 Participants |
| Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 7 Participants |
| Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 14 Participants |
| Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC) | Number of Participants With One or More AEs | 30 Participants |
| Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial) | Number of Participants With One or More AEs | 15 Participants |
| Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial) | Number of Participants With One or More AEs | 13 Participants |
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Number of Participants With One or More AEs | 1 Participants |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Number of Participants With One or More AEs | 1 Participants |
| Switch-over Arm 1 Boserolimab 20 mg Q3W To Boserolimab 7 mg + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 2 Participants |
| Switch-over Arm 1 Boserolimab 20 mg Q3W To Boserolimab 20 mg + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 3 Participants |
| Switch-over Arm 1 Boserolimab 70 mg Q3W To Boserolimab 20 mg + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 2 Participants |
| Switch-over Arm 1 Boserolimab 200 mg Q3W To Boserolimab 20 mg + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 2 Participants |
| Switch-over Arm 1 Boserolimab 200 mg Q3W To Boserolimab 70 mg + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 2 Participants |
| Switch-over Arm 1 Boserolimab 200 mg Q3W To Boserolimab 200 mg + Pembrolizumab 200 mg Q3W | Number of Participants With One or More AEs | 1 Participants |
| Switch-over Arm 1a Boserolimab 30mg Q3W (Endometrial) To Boserolimab 30mg + Pembrolizumab 200mg Q3W | Number of Participants With One or More AEs | 8 Participants |
Secondary
Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab
AUC0-3w was defined as the area under the concentration versus time curve for boserolimab from 0 to 3 weeks in serum. Samples were taken predose and at specified times postdose to determine the AUC0-3w of boserolimab. PK collection time frames include: Arms 1, 2 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 5, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 1a, 2a, 2b, 3 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1.
Time frame: Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2
Population: All participants who complied with the protocol sufficiently to ensure that the data was likely to exhibit the effects of treatment, according to the underlying scientific model, and who had available AUC0-3w data from ≥1 study treatment. As pre-specified in the protocol, PK outcomes were not analyzed separately for the Switch-over Arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 1.79 day*μg/mL | Geometric Coefficient of Variation 111 |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 7.77 day*μg/mL | — |
| Arm 1 Boserolimab 20 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 44.4 day*μg/mL | Geometric Coefficient of Variation 28.6 |
| Arm 1 Boserolimab 70 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 155 day*μg/mL | Geometric Coefficient of Variation 7.85 |
| Arm 1 Boserolimab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 531 day*μg/mL | Geometric Coefficient of Variation 28.1 |
| Arm 1 Boserolimab 700 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 1060 day*μg/mL | Geometric Coefficient of Variation 0.434 |
| Arm 1a Boserolimab 30 mg Q3W (Endometrial) | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 44.3 day*μg/mL | Geometric Coefficient of Variation 54 |
| Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 1.2 day*μg/mL | Geometric Coefficient of Variation 22 |
| Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 6.69 day*μg/mL | Geometric Coefficient of Variation 47.5 |
| Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 28.1 day*μg/mL | Geometric Coefficient of Variation 50.8 |
| Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 142 day*μg/mL | Geometric Coefficient of Variation 63.3 |
| Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 661 day*μg/mL | Geometric Coefficient of Variation 16.4 |
| Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC) | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 49.9 day*μg/mL | Geometric Coefficient of Variation 41.3 |
| Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial) | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 50.5 day*μg/mL | Geometric Coefficient of Variation 34.2 |
| Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial) | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 48.1 day*μg/mL | Geometric Coefficient of Variation 42.5 |
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 42.2 day*μg/mL | Geometric Coefficient of Variation 41.5 |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab | 60.4 day*μg/mL | Geometric Coefficient of Variation 39.5 |
Secondary
Area Under the Concentration-Time Curve From Time 0 to 6 Weeks (AUC0-6w) of Boserolimab
AUC0-6w was defined as the area under the concentration versus time curve for boserolimab from 0 to 6 weeks in serum. Samples were taken predose and at specified times postdose to determine the AUC0-6w of boserolimab. As pre-specified in the protocol, different arms had different sampling schedules and cycle lengths and therefore AUC0-6w was not analyzed for all Arms; AUC0-6w was only analyzed for Arms 2c and 4 which had 6-week cycles.
Time frame: Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1, and predose on Day 1 Cycle 2
Population: All participants in Arms 2c and 4 who complied with the protocol sufficiently to ensure that the data was likely to exhibit the effects of treatment, according to the underlying scientific model, and who had available AUC0-6w data from ≥1 study treatment. As pre-specified in the protocol, PK outcomes were not analyzed separately for the Switch-over Arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Area Under the Concentration-Time Curve From Time 0 to 6 Weeks (AUC0-6w) of Boserolimab | 55 day*μg/mL | Geometric Coefficient of Variation 49.2 |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Area Under the Concentration-Time Curve From Time 0 to 6 Weeks (AUC0-6w) of Boserolimab | 68.3 day*μg/mL | Geometric Coefficient of Variation 45.4 |
Secondary
Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab
AUC0-last was defined as the area under the concentration versus time curve for boserolimab from 0 to the time of the last quantifiable concentration in serum. Samples were taken predose and at specified times postdose to determine the AUC0-last of boserolimab. PK collection time frames include: Arms 1, 2 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 5, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 1a, 2a, 2b, 3 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1, and predose on Day 1 of Cycle 2.
Time frame: Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2
Population: All participants who complied with the protocol sufficiently to ensure that the data was likely to exhibit the effects of treatment, according to the underlying scientific model, and who had available AUC0-last data from ≥1 study treatment. As pre-specified in the protocol, PK outcomes were not analyzed separately for the Switch-over Arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 0.761 day*μg/mL | Geometric Coefficient of Variation 179 |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 7.61 day*μg/mL | — |
| Arm 1 Boserolimab 20 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 44.4 day*μg/mL | Geometric Coefficient of Variation 28.6 |
| Arm 1 Boserolimab 70 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 150 day*μg/mL | Geometric Coefficient of Variation 14.2 |
| Arm 1 Boserolimab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 469 day*μg/mL | Geometric Coefficient of Variation 42.9 |
| Arm 1 Boserolimab 700 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 918 day*μg/mL | Geometric Coefficient of Variation 21.4 |
| Arm 1a Boserolimab 30 mg Q3W (Endometrial) | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 44.4 day*μg/mL | Geometric Coefficient of Variation 51.7 |
| Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 0.816 day*μg/mL | Geometric Coefficient of Variation 20.8 |
| Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 3.9 day*μg/mL | Geometric Coefficient of Variation 117 |
| Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 26.1 day*μg/mL | Geometric Coefficient of Variation 38.5 |
| Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 84.5 day*μg/mL | Geometric Coefficient of Variation 192 |
| Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 646 day*μg/mL | Geometric Coefficient of Variation 16.3 |
| Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC) | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 41.5 day*μg/mL | Geometric Coefficient of Variation 109 |
| Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial) | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 44.9 day*μg/mL | Geometric Coefficient of Variation 68.6 |
| Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial) | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 47.5 day*μg/mL | Geometric Coefficient of Variation 58.5 |
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 41.6 day*μg/mL | Geometric Coefficient of Variation 44.5 |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab | 62.9 day*μg/mL | Geometric Coefficient of Variation 57.8 |
Secondary
Arm 3 and 4: Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Arms 3 or 4 who discontinued study treatment due to an AE is reported.
Time frame: Up to 27 months
Population: All participants in Arms 3 or 4 who received ≥1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Arm 3 and 4: Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Arm 3 and 4: Number of Participants Who Discontinued Study Treatment Due to an AE | 6 Participants |
Secondary
Arm 3 and 4: Number of Participants With One or More AEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Arms 3 and 4 who experienced one or more AEs is reported.
Time frame: Up to 57 months
Population: All participants in Arms 3 or 4 who received ≥1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Arm 3 and 4: Number of Participants With One or More AEs | 10 Participants |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Arm 3 and 4: Number of Participants With One or More AEs | 41 Participants |
Secondary
Arm 3: Number of Participants Who Experienced a DLT
DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. A DLT was defined as any of the following events: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia requiring a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality; Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study drug discontinuation during the DLT evaluation period; Missing \>25% of any study drug during the DLT evaluation period due to a treatment-related AE; or Grade 5 toxicity. The number of participants who experienced one or more DLTs in Arm 3 is reported
Time frame: Up to 21 days in Cycle 1
Population: All participants in Arm 3 who received ≥1 dose of study treatment and who were observed for DLTs for up to 21 days following the first dose of study treatment in Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Arm 3: Number of Participants Who Experienced a DLT | 0 Participants |
Secondary
Arm 4: Number of Participants Who Experienced a DLT
DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. A DLT was defined as any of the following events: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia requiring a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality; Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study drug discontinuation during the DLT evaluation period; Missing \>25% of any study drug during the DLT evaluation period due to a treatment-related AE; or Grade 5 toxicity. The number of participants who experienced one or more DLTs in Arm 4 is reported.
Time frame: Up to 28 days in Cycle 1
Population: All participants in Arm 4 who received ≥1 dose of study treatment and who were observed for DLTs for up to 28 days following the first dose of study treatment in Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Arm 4: Number of Participants Who Experienced a DLT | 1 Participants |
Secondary
Maximum Concentration (Cmax) of Boserolimab
Cmax of boserolimab was defined as the maximum concentration of boserolimab observed in serum. Samples were taken predose and at specified times postdose to determine the Cmax of boserolimab. PK collection time frames include: Arms 1, 2 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 5, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 1a, 2a, 2b, 3 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1, and predose on Day 1 of Cycle 2.
Time frame: Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2
Population: All participants who complied with the protocol sufficiently to ensure that the data was likely to exhibit the effects of treatment, according to the underlying scientific model, and who had available Cmax data from ≥1 study treatment. As pre-specified in the protocol, PK outcomes were not analyzed separately for the Switch-over Arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Maximum Concentration (Cmax) of Boserolimab | 1.15 μg/mL | Geometric Coefficient of Variation 175 |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Maximum Concentration (Cmax) of Boserolimab | 3.32 μg/mL | — |
| Arm 1 Boserolimab 20 mg Q3W | Maximum Concentration (Cmax) of Boserolimab | 8.16 μg/mL | Geometric Coefficient of Variation 28.6 |
| Arm 1 Boserolimab 70 mg Q3W | Maximum Concentration (Cmax) of Boserolimab | 21.6 μg/mL | Geometric Coefficient of Variation 22 |
| Arm 1 Boserolimab 200 mg Q3W | Maximum Concentration (Cmax) of Boserolimab | 67.8 μg/mL | Geometric Coefficient of Variation 23.1 |
| Arm 1 Boserolimab 700 mg Q3W | Maximum Concentration (Cmax) of Boserolimab | 105 μg/mL | Geometric Coefficient of Variation 8.71 |
| Arm 1a Boserolimab 30 mg Q3W (Endometrial) | Maximum Concentration (Cmax) of Boserolimab | 7.24 μg/mL | Geometric Coefficient of Variation 46.7 |
| Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W | Maximum Concentration (Cmax) of Boserolimab | 0.656 μg/mL | Geometric Coefficient of Variation 5.08 |
| Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W | Maximum Concentration (Cmax) of Boserolimab | 1.75 μg/mL | Geometric Coefficient of Variation 5.75 |
| Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W | Maximum Concentration (Cmax) of Boserolimab | 4.9 μg/mL | Geometric Coefficient of Variation 39 |
| Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W | Maximum Concentration (Cmax) of Boserolimab | 26.9 μg/mL | Geometric Coefficient of Variation 37 |
| Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W | Maximum Concentration (Cmax) of Boserolimab | 83.2 μg/mL | Geometric Coefficient of Variation 16.6 |
| Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC) | Maximum Concentration (Cmax) of Boserolimab | 7.89 μg/mL | Geometric Coefficient of Variation 70.2 |
| Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial) | Maximum Concentration (Cmax) of Boserolimab | 8.68 μg/mL | Geometric Coefficient of Variation 24.6 |
| Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial) | Maximum Concentration (Cmax) of Boserolimab | 8.27 μg/mL | Geometric Coefficient of Variation 37.4 |
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Maximum Concentration (Cmax) of Boserolimab | 7.44 μg/mL | Geometric Coefficient of Variation 37.3 |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Maximum Concentration (Cmax) of Boserolimab | 9.39 μg/mL | Geometric Coefficient of Variation 33.2 |
Secondary
Minimum Concentration (Cmin) of Boserolimab
Cmin of boserolimab was defined as the minimum concentration of boserolimab observed in serum. Samples were taken predose and at specified times postdose to determine the Cmin of boserolimab. PK collection time frames include: Arms 1, 2 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 5, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 1a, 2a, 2b, 3 (Cycle = 3 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15 of Cycle 1, and predose on Day 1 of Cycle 2; Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1, and predose on Day 1 of Cycle 2.
Time frame: Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2
Population: All participants who complied with the protocol sufficiently to ensure that the data was likely to exhibit the effects of treatment, according to the underlying scientific model, and who had available Cmin data from ≥1 study treatment. As pre-specified in the protocol, PK outcomes were not analyzed separately for the Switch-over Arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Minimum Concentration (Cmin) of Boserolimab | NA μg/mL | — |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Minimum Concentration (Cmin) of Boserolimab | 0.0689 μg/mL | Standard Deviation 0.0975 |
| Arm 1 Boserolimab 20 mg Q3W | Minimum Concentration (Cmin) of Boserolimab | 0.421 μg/mL | Standard Deviation 0.103 |
| Arm 1 Boserolimab 70 mg Q3W | Minimum Concentration (Cmin) of Boserolimab | 3.55 μg/mL | Standard Deviation 0.573 |
| Arm 1 Boserolimab 200 mg Q3W | Minimum Concentration (Cmin) of Boserolimab | 15.5 μg/mL | Standard Deviation 8.08 |
| Arm 1 Boserolimab 700 mg Q3W | Minimum Concentration (Cmin) of Boserolimab | 24.3 μg/mL | — |
| Arm 1a Boserolimab 30 mg Q3W (Endometrial) | Minimum Concentration (Cmin) of Boserolimab | 0.617 μg/mL | Standard Deviation 0.498 |
| Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W | Minimum Concentration (Cmin) of Boserolimab | NA μg/mL | — |
| Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W | Minimum Concentration (Cmin) of Boserolimab | 0.0283 μg/mL | Standard Deviation 0.04 |
| Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W | Minimum Concentration (Cmin) of Boserolimab | 0.0629 μg/mL | Standard Deviation 0.0575 |
| Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W | Minimum Concentration (Cmin) of Boserolimab | 3.55 μg/mL | Standard Deviation 3.37 |
| Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W | Minimum Concentration (Cmin) of Boserolimab | 16.2 μg/mL | Standard Deviation 5.14 |
| Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC) | Minimum Concentration (Cmin) of Boserolimab | 0.721 μg/mL | Standard Deviation 0.505 |
| Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial) | Minimum Concentration (Cmin) of Boserolimab | 0.610 μg/mL | Standard Deviation 0.499 |
| Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial) | Minimum Concentration (Cmin) of Boserolimab | 0.126 μg/mL | Standard Deviation 0.258 |
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Minimum Concentration (Cmin) of Boserolimab | 0.471 μg/mL | Standard Deviation 0.473 |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Minimum Concentration (Cmin) of Boserolimab | 0.158 μg/mL | Standard Deviation 0.34 |
Secondary
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
ORR was defined as the percentage of participants who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. As pre-specified in the protocol, ORR was analyzed for participants treated with boserolimab when used as monotherapy in Arm 1a, in combination with pembrolizumab in Switch-over Arm 1a and Arms 2a, 2b, and 2c, or in combination with pembrolizumab + nab-paclitaxel in Arm 4. Per protocol, ORR was not analyzed in Arms 1, 2, or 3. The percentage of participants who experienced a CR or PR, as assessed by the investigator, is reported.
Time frame: Up to approximately 78 months
Population: All participants in Arm 1a, 2a, 2b, 2c, 4, and Switch-over Arm 1a with a baseline scan who demonstrated measurable disease by investigator assessment, and who were administered at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC) | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 7.1 Percentage of Participants |
| Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC) | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 20.0 Percentage of Participants |
| Arm 1 Boserolimab 20 mg Q3W | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 13.3 Percentage of Participants |
| Arm 1 Boserolimab 70 mg Q3W | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 0.0 Percentage of Participants |
| Arm 1 Boserolimab 200 mg Q3W | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 53.7 Percentage of Participants |
| Arm 1 Boserolimab 700 mg Q3W | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 11.1 Percentage of Participants |
Comparison: Difference in percentage of participants who experienced a CR or PR (Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W \[Endometrial\] - Arm 1a Boserolimab 30 mg Q3W \[Endometrial\])95% CI: [-21.2, 32.8]
Comparison: Difference in percentage of participants who experienced a CR or PR (Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W \[Endometrial\] - Arm 1a Boserolimab 30 mg \[Endometrial\])95% CI: [-32.1, 17.2]
Comparison: Difference in percentage of participants who experienced a CR or PR (Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W \[Endometrial\] - Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W \[Endometrial\])95% CI: [-11.7, 38.4]