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

Study Overview
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Brief Summary
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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 with advanced solid tumors. The initial course of boserolimab monotherapy or boserolimab plus pembrolizumab combination therapy will be 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
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Participants receiving boserolimab monotherapy who experience disease progression may be eligible to switch to receiving boserolimab plus pembrolizumab combination therapy for up to 35 cycles (approximately 2 years) at the discretion of the Investigator and approval of the Sponsor.

Official Title
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A Phase 1 Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

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

Intervention / Treatment
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* Drug: Boserolimab
* Biological: Pembrolizumab
* Drug: Pemetrexed
* Drug: Carboplatin
* Drug: Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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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 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Boserolimab<br>Participants receive escalating doses of boserolimab via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years). | Drug: Boserolimab<br>* IV infusion<br>* Other names: MK-5890;|
| Experimental: Arm 2: Boserolimab + Pembrolizumab<br>Participants receive escalating doses of boserolimab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years). | Drug: Boserolimab<br>* IV infusion<br>* Other names: MK-5890;Biological: Pembrolizumab<br>* IV infusion<br>* Other names: MK-3475;|
| Experimental: Arm 3: Boserolimab + Pembrolizumab + Pemetrexed + Carboplatin<br>Participants receive boserolimab at the selected dose via IV infusion PLUS pembrolizumab 200 mg via IV infusion PLUS pemetrexed 500 mg/m^2 via IV infusion PLUS carboplatin Area Under the Curve (AUC) 5 mg/mL/min via IV infusion, all given on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years). | Drug: Boserolimab<br>* IV infusion<br>* Other names: MK-5890;Biological: Pembrolizumab<br>* IV infusion<br>* Other names: MK-3475;Drug: Pemetrexed<br>* IV infusion<br>* Other names: ALIMTA®;Drug: Carboplatin<br>* IV infusion<br>* Other names: PARAPLATIN®;|
| Experimental: Arm 4: Boserolimab + Pembrolizumab + Nab-paclitaxel<br>Participants receive boserolimab at the selected dose via IV infusion PLUS pembrolizumab via IV infusion PLUS nab-paclitaxel 100 mg/m^2 via IV infusion. Boserolimab and pembrolizumab will be given on Day 1 of each 6-week cycle (Q6W). Nab-paclitaxel will be given on a 3-week on (Days 1, 8 and 15)/ 1-week off schedule every 28 days. Boserolimab and pembrolizumab will be given for up to a total of 18 cycles (approximately 2 years). | Drug: Boserolimab<br>* IV infusion<br>* Other names: MK-5890;Biological: Pembrolizumab<br>* IV infusion<br>* Other names: MK-3475;Drug: Nab-paclitaxel<br>* IV infusion<br>* Other names: ABRAXANE®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arms 1 and 2: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later | A DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia associated with bleeding that requires a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3 in severity, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required or if abnormality leads to hospitalization, persists for >1 week or results in drug-induced liver injury with exceptions; Grade 3 or 4 febrile neutropenia; Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study treatment discontinuation during Cycle 1; Missing >25% of any study drug during the DLT evaluation period as a result of a drug-related AE; Grade 5 toxicity. | Cycle 1 (Up to 21 days) | 
| Arms 1 and 2: Number of Participants with Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Arms 1 and 2 who experience at least one AE will be presented. | Up to 27 months | 
| Arms 1 and 2: Number of Study Treatment Discontinuations Due to an Adverse Event (AE) | The number of participants in Arms 1 and 2 who discontinue study treatment due to an AE will be presented. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Arms: Area Under the Concentration-Time Curve (AUC) of boserolimab | Blood samples will be obtained at designated time points for the assessment of boserolimab AUC: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of boserolimab infusion, 2 hours post start of boserolimab infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. Each cycle is 21 days. (Up to 25 months) | At designated time points (Up to 25 months) | 
| All Arms: Minimum Serum Concentration (Cmin) of boserolimab | Blood samples will be obtained at designated time points for the assessment of boserolimab Cmin: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of boserolimab infusion, 2 hours post start of boserolimab infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. Each cycle is 21 days. (Up to 25 months) | At designated time points (Up to 25 months) | 
| All Arms: Maximum Serum Concentration (Cmax) of boserolimab | Blood samples will be obtained at designated time points for the assessment of boserolimab Cmax: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of boserolimab infusion, 2 hours post start of boserolimab infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. Each cycle is 21 days. (Up to 25 months) | At designated time points (Up to 25 months) | 
| Arms 1, 2, and 4: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | The ORR is defined as the percentage of participants who have 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) per RECIST 1.1. The ORR of boserolimab when used as monotherapy, in combination with pembrolizumab (Arms 1 and 2), and in combination with pembrolizumab PLUS nab-paclitaxel (Arm 4) as assessed by the investigator will be presented. | Up to 24 months | 
| Arm 3: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later | A DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia associated with bleeding that requires a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3 in severity, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required or if abnormality leads to hospitalization, persists for >1 week or results in drug-induced liver injury with exceptions; Grade 3 or 4 febrile neutropenia; Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study treatment discontinuation during Cycle 1; Missing >25% of any study drug during the DLT evaluation period as a result of a drug-related AE; Grade 5 toxicity. | Cycle 1 (Up to 21 days) | 
| Arm 4: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later | A DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia associated with bleeding that requires a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3 in severity, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required or if abnormality leads to hospitalization, persists for >1 week or results in drug-induced liver injury with exceptions; Grade 3 or 4 febrile neutropenia; Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study treatment discontinuation during Cycle 1; Missing >25% of any study drug during the DLT evaluation period as a result of a drug-related AE; Grade 5 toxicity. | Cycle 1 (Up to 28 days) | 
| Arms 3 and 4: Number of Participants with Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a 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 experience at least one AE will be presented. | Up to 27 months | 
| Arms 3 and 4: Number of Study Treatment Discontinuations Due to an Adverse Event (AE) | The number of participants in Arms 3 and 4 who discontinue study treatment due to an AE will be presented. | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-1, Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), Programmed Cell Death Receptor Ligand 2 (PD-L2), PDL1, PD-L1, PD-L2