Study of Boserolimab (MK-5890) as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Adults With Advanced Solid Tumors (MK-5890-001)

Phase 1

Completed

Conditions: Solid Tumor
Pharmacokinetics
Carcinoma, Non-Small-Cell Lung
Triple Negative Breast Neoplasms

Interventions: Drug: Boserolimab
Biological: Pembrolizumab
Drug: Pemetrexed
Drug: Nab-paclitaxel
Drug: Carboplatin

Registration Number: NCT03396445

Lead Sponsor: Merck Sharp & Dohme LLC

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 182

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 Exclusion Criteria for Participants in Arm 3:

Has received radiation therapy to the lung that is >30 Gray (Gy) within 6 months before the first dose of study treatment
Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
Is unable or unwilling to take folic acid or vitamin B12 supplementation

Additional Exclusion Criteria for Participants in Arm 4:

Has a known history of hypersensitivity or allergy to nab-paclitaxel or any of its components
Has neuropathy ≥Grade 2
Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of randomization
Has received previous treatment with immune checkpoint inhibitor(s) (eg, Programmed Cell Death Receptor 1 (PD-1)/PD-L1)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1 Boserolimab 2 mg Q3W	Boserolimab	Participants receive boserolimab 2 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 is 3 weeks long.
Arm 1 Boserolimab 7 mg Q3W	Boserolimab	Participants receive boserolimab 7 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 is 3 weeks long.
Arm 1 Boserolimab 20 mg Q3W	Boserolimab	Participants receive 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 is 3 weeks long.
Arm 1 Boserolimab 70 mg Q3W	Boserolimab	Participants receive 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 is 3 weeks long.
Arm 1 Boserolimab 200 mg Q3W	Boserolimab	Participants receive 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 is 3 weeks long.
Arm 1 Boserolimab 700 mg Q3W	Boserolimab	Participants receive 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 is 3 weeks long.
Arm 1a Boserolimab 30 mg Q3W (Endometrial)	Boserolimab	Participants with endometrial cancer receive 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 is 3 weeks long.
Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W	Boserolimab	Participants receive separate IV infusions of boserolimab 2 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W	Pembrolizumab	Participants receive separate IV infusions of boserolimab 2 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W	Boserolimab	Participants receive separate IV infusions of boserolimab 7 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W	Pembrolizumab	Participants receive separate IV infusions of boserolimab 7 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W	Boserolimab	Participants receive separate IV infusions of boserolimab 20 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W	Pembrolizumab	Participants receive separate IV infusions of boserolimab 20 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W	Boserolimab	Participants receive separate IV infusions of boserolimab 70 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W	Pembrolizumab	Participants receive separate IV infusions of boserolimab 70 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W	Boserolimab	Participants receive separate IV infusions of boserolimab 200 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W	Pembrolizumab	Participants receive separate IV infusions of boserolimab 200 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC)	Boserolimab	Participants with triple-negative breast cancer (TNBC) receive separate IV infusions of boserolimab 30 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC)	Pembrolizumab	Participants with triple-negative breast cancer (TNBC) receive separate IV infusions of boserolimab 30 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial)	Boserolimab	Participants with endometrial cancer receive separate IV infusions of boserolimab 30 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial)	Pembrolizumab	Participants with endometrial cancer receive separate IV infusions of boserolimab 30 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are 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 is 3 weeks long.
Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial)	Boserolimab	Participants with endometrial cancer receive separate IV infusions of boserolimab 30 mg and pembrolizumab 400 mg. Boserolimab was administered once every 6 weeks (Q6W) on Day 1 of each cycle for a total of up to approximately 4 cycles (up to approximately 6 months). Pembrolizumab is 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 is 6 weeks long.
Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial)	Pembrolizumab	Participants with endometrial cancer receive separate IV infusions of boserolimab 30 mg and pembrolizumab 400 mg. Boserolimab was administered once every 6 weeks (Q6W) on Day 1 of each cycle for a total of up to approximately 4 cycles (up to approximately 6 months). Pembrolizumab is 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 is 6 weeks long.
Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC)	Boserolimab	Participants with non-small cell lung cancer (NSCLC) receive 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 is 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 are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Carboplatin is 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 is 3 weeks long.
Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC)	Pembrolizumab	Participants with non-small cell lung cancer (NSCLC) receive 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 is 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 are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Carboplatin is 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 is 3 weeks long.
Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC)	Pemetrexed	Participants with non-small cell lung cancer (NSCLC) receive 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 is 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 are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Carboplatin is 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 is 3 weeks long.
Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC)	Carboplatin	Participants with non-small cell lung cancer (NSCLC) receive 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 is 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 are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Carboplatin is 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 is 3 weeks long.
Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC)	Boserolimab	Participants with TNBC receive separate IV infusions of boserolimab 30 mg, pembrolizumab 400 mg, and nab-paclitaxel 100 mg/m\^2. Boserolimab and pembrolizumab are 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 is 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 is 6 weeks long
Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC)	Pembrolizumab	Participants with TNBC receive separate IV infusions of boserolimab 30 mg, pembrolizumab 400 mg, and nab-paclitaxel 100 mg/m\^2. Boserolimab and pembrolizumab are 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 is 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 is 6 weeks long
Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC)	Nab-paclitaxel	Participants with TNBC receive separate IV infusions of boserolimab 30 mg, pembrolizumab 400 mg, and nab-paclitaxel 100 mg/m\^2. Boserolimab and pembrolizumab are 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 is 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 is 6 weeks long

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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
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.

Trial Locations

Locations (18): University of South Alabama, Mitchell Cancer Institute ( Site 0020)
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Mobile, Alabama, United States
Florida Cancer Specialists ( Site 0002)
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Sarasota, Florida, United States
The West Clinic, P.C. ( Site 0021)
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Germantown, Tennessee, United States
FALP-UIDO ( Site 0502)
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Santiago, Region M. de Santiago, Chile
Bradfordhill-Clinical Area ( Site 0501)
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Santiago, Region M. de Santiago, Chile
Soroka Medical Center-Oncology ( Site 0012)
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Beersheba, Israel
Hadassah Ein Kerem Medical Center ( Site 0010)
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Jerusalem, Israel
The Chaim Sheba Medical Center - Oncology Institute ( Site 0001)
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Ramat Gan, Israel
Antoni van Leeuwenhoek Ziekenhuis ( Site 0003)
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Amsterdam, North Holland, Netherlands
Erasmus MC ( Site 0031)
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Rotterdam, South Holland, Netherlands
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University of South Alabama, Mitchell Cancer Institute ( Site 0020)
🇺🇸Mobile, Alabama, United States