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

Merck Sharp & Dohme LLC182 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

182

Conditions

Pharmacokinetics Solid Tumor

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (18)

University of South Alabama, Mitchell Cancer Institute ( Site 0020)

Mobile, Alabama, United States

Florida Cancer Specialists ( Site 0002)

Sarasota, Florida, United States

The West Clinic, P.C. ( Site 0021)

Germantown, Tennessee, United States

FALP-UIDO ( Site 0502)

Santiago, Region M. de Santiago, Chile

Bradfordhill-Clinical Area ( Site 0501)

Santiago, Region M. de Santiago, Chile

Soroka Medical Center-Oncology ( Site 0012)

Beersheba, Israel

Hadassah Ein Kerem Medical Center ( Site 0010)

Jerusalem, Israel

The Chaim Sheba Medical Center - Oncology Institute ( Site 0001)

Ramat Gan, Israel

Antoni van Leeuwenhoek Ziekenhuis ( Site 0003)

Amsterdam, North Holland, Netherlands

Erasmus MC ( Site 0031)

Rotterdam, South Holland, Netherlands

...and 8 more locations

Outcomes

Primary Outcomes

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

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

Number of Participants Who Discontinued Study Treatment Due to an AE

Time frame: Up to 23 months

Secondary Outcomes

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

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

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

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

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

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

Arm 3: Number of Participants Who Experienced a DLT

Time frame: Up to 21 days in Cycle 1

Arm 4: Number of Participants Who Experienced a DLT

Time frame: Up to 28 days in Cycle 1

Arm 3 and 4: Number of Participants With One or More AEs

Time frame: Up to 57 months

Arm 3 and 4: Number of Participants Who Discontinued Study Treatment Due to an AE

Time frame: Up to 27 months

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

Overview

Conditions

Interventions

Eligibility

Locations (18)

Outcomes

Primary Outcomes

Secondary Outcomes