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 (MSD)

Status and phase: Completed; Phase 1

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

Treatments: Drug: Nab-paclitaxel; Biological: Pembrolizumab; Drug: Carboplatin; Drug: Pemetrexed; Drug: Boserolimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03396445

2017-004550-41 (EudraCT Number)

MK-5890-001 (Other Identifier)

5890-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 182 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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182 participants in 17 patient groups

Arm 1 Boserolimab 2 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Arm 1 Boserolimab 7 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Arm 1 Boserolimab 20 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Arm 1 Boserolimab 70 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Arm 1 Boserolimab 200 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Arm 1 Boserolimab 700 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Arm 1a Boserolimab 30 mg Q3W (Endometrial)

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Biological: Pembrolizumab

Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Biological: Pembrolizumab

Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Biological: Pembrolizumab

Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Biological: Pembrolizumab

Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Biological: Pembrolizumab

Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC)

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Biological: Pembrolizumab

Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial)

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Biological: Pembrolizumab

Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial)

Experimental group

Description:

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.

Treatment:

Drug: Boserolimab

Biological: Pembrolizumab

Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC)

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Boserolimab

Drug: Carboplatin

Biological: Pembrolizumab

Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC)

Experimental group

Description:

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

Treatment:

Drug: Boserolimab

Biological: Pembrolizumab

Drug: Nab-paclitaxel