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

• ClinicalTrials.gov Identifier: NCT03396445
• Recruitment Status: Active, not recruiting
• First Posted: January 11, 2018
• Last Update Posted: April 11, 2023
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: January 4, 2018
• First Posted Date: January 11, 2018
• Last Update Posted Date: April 11, 2023
• Actual Study Start Date: February 18, 2018
• Estimated Primary Completion Date: October 25, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2021)

• Arms 1 and 2: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later [ Time Frame: Cycle 1 (Up to 21 days) ]
  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.
• Arms 1 and 2: Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 27 months ]
  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.
• Arms 1 and 2: Number of Study Treatment Discontinuations Due to an Adverse Event (AE) [ Time Frame: Up to 24 months ]
  The number of participants in Arms 1 and 2 who discontinue study treatment due to an AE will be presented.

Original Primary Outcome Measures (submitted: January 4, 2018)

• Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later [ Time Frame: Cycle 1 (Up to 21 days) ]
  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 Grade 4 febrile neutropenia;
  • Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity;
  • Treatment-related toxicity resulting in participant study treatment discontinuation during Cycle 1;
  • Missing >25% of the MK-5890 dose during Cycle 1 resulting from treatment-related AE;
  • Grade 5 toxicity.
• Adverse Events (AEs) [ Time Frame: Up to 27 months ]
  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 who experience at least one AE will be presented.
• Study Treatment Discontinuations Due to an AE [ Time Frame: Up to 24 months ]
  The number of participants who discontinue study treatment due to an AE will be presented.

Current Secondary Outcome Measures (submitted: April 10, 2023)

• All Arms: Area Under the Concentration-Time Curve (AUC) of boserolimab [ Time Frame: At designated time points (Up to 25 months) ]
  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)
• All Arms: Minimum Serum Concentration (Cmin) of boserolimab [ Time Frame: At designated time points (Up to 25 months) ]
  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)
• All Arms: Maximum Serum Concentration (Cmax) of boserolimab [ Time Frame: At designated time points (Up to 25 months) ]
  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)
• Arms 1, 2, and 4: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to 24 months ]
  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.
• Arm 3: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later [ Time Frame: Cycle 1 (Up to 21 days) ]
  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.
• Arm 4: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later [ Time Frame: Cycle 1 (Up to 28 days) ]
  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.
• Arms 3 and 4: Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 27 months ]
  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.
• Arms 3 and 4: Number of Study Treatment Discontinuations Due to an Adverse Event (AE) [ Time Frame: Up to 24 months ]
  The number of participants in Arms 3 and 4 who discontinue study treatment due to an AE will be presented.

Original Secondary Outcome Measures (submitted: January 4, 2018)

• Area Under the Concentration-Time Curve (AUC) of MK-5890 When Administered as Monotherapy and in Combination with Pembrolizumab [ Time Frame: At designated time points (Up to 25 months) ]
  Blood samples will be obtained at designated time points for the assessment of MK-5890 AUC: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. (Up to 25 months)
• Minimum Serum Concentration (Cmin) of MK-5890 When Administered as Monotherapy and in Combination with Pembrolizumab [ Time Frame: At designated time points (Up to 25 months) ]
  Blood samples will be obtained at designated time points for the assessment of MK-5890 Cmin: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. (Up to 25 months)
• Maximum Serum Concentration (Cmin) of MK-5890 When Administered as Monotherapy and in Combination with Pembrolizumab [ Time Frame: At designated time points (Up to 25 months) ]
  Blood samples will be obtained at designated time points for the assessment of MK-5890 Cmax: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. (Up to 25 months)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Boserolimab (MK-5890) as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Adults With Advanced Solid Tumors (MK-5890-001)
• Official Title: A Phase 1 Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
• 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 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: 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Boserolimab
  IV infusion
  Other Name: MK-5890
• Biological: Pembrolizumab
  IV infusion
  Other Name: MK-3475
• Drug: Pemetrexed
  IV infusion
  Other Name: ALIMTA®
• Drug: Carboplatin
  IV infusion
  Other Name: PARAPLATIN®
• Drug: Nab-paclitaxel
  IV infusion
  Other Name: ABRAXANE®

Study Arms

• Experimental: Arm 1: Boserolimab
  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).
  Intervention: Drug: Boserolimab
• Experimental: Arm 2: Boserolimab + Pembrolizumab
  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).
  Interventions:

  • Drug: Boserolimab
  • Biological: Pembrolizumab
• Experimental: Arm 3: Boserolimab + Pembrolizumab + Pemetrexed + Carboplatin
  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).
  Interventions:

  • Drug: Boserolimab
  • Biological: Pembrolizumab
  • Drug: Pemetrexed
  • Drug: Carboplatin
• Experimental: Arm 4: Boserolimab + Pembrolizumab + Nab-paclitaxel
  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).
  Interventions:

  • Drug: Boserolimab
  • Biological: Pembrolizumab
  • Drug: Nab-paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: February 9, 2021): 202
• Original Estimated Enrollment (submitted: January 4, 2018): 88
• Estimated Study Completion Date: October 25, 2024
• Estimated Primary Completion Date: October 25, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Chile, Israel, Korea, Republic of, Netherlands, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT03396445
• Other Study ID Numbers: 5890-001; MK-5890-001 ( Other Identifier: Merck Protocol Number ); 2017-004550-41 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: April 2023