Clinical trial NCT03396445: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Solid Tumor
Carcinoma, Non-Small-Cell Lung
Triple Negative Breast Neoplasms
Keywords: Programmed Cell Death Receptor 1 (PD-1)
Programmed Cell Death Receptor Ligand 1 (PD-L1)
Programmed Cell Death Receptor Ligand 2 (PD-L2)
PD-1
PDL1
PD-L1
PD-L2
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-01-11
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Arms 1 and 2: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later
timeFrame: Cycle 1 (Up to 21 days)
measure: Arms 1 and 2: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 27 months
measure: Arms 1 and 2: Number of Study Treatment Discontinuations Due to an Adverse Event (AE)
timeFrame: Up to 24 months
Secondary outcomes:
measure: All Arms: Area Under the Concentration-Time Curve (AUC) of boserolimab
timeFrame: At designated time points (Up to 25 months)
measure: All Arms: Minimum Serum Concentration (Cmin) of boserolimab
timeFrame: At designated time points (Up to 25 months)
measure: All Arms: Maximum Serum Concentration (Cmax) of boserolimab
timeFrame: At designated time points (Up to 25 months)
measure: Arms 1, 2, and 4: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to 24 months
measure: Arm 3: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later
timeFrame: Cycle 1 (Up to 21 days)
measure: Arm 4: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later
timeFrame: Cycle 1 (Up to 28 days)
measure: Arms 3 and 4: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 27 months
measure: Arms 3 and 4: Number of Study Treatment Discontinuations Due to an Adverse Event (AE)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama, Mitchell Cancer Institute ( Site 0020)
state: Alabama
city: Sarasota
country: United States
facility: Florida Cancer Specialists ( Site 0002)
state: Florida
city: Germantown
country: United States
facility: The West Clinic, P.C. ( Site 0021)
state: Tennessee
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 0502)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradfordhill-Clinical Area ( Site 0501)
state: Region M. De Santiago
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center-Oncology ( Site 0012)
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center ( Site 0010)
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center - Oncology Institute ( Site 0001)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital-Internal Medicine ( Site 0702)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System-Medical oncology ( Site 0701)
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis ( Site 0003)
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC ( Site 0031)
state: Zuid-Holland
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Madrid ( Site 0043)
state: Madrid
city: Barcelona
country: Spain
facility: Instituto Catalan de Oncologia - ICO ( Site 0044)
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz ( Site 0041)
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal START Madrid ( Site 0040)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital-Oncology ( Site 0801)
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center ( Site 0802)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: