Clinical trial NCT05394350: A Study of MK-1088 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (MK-1088-002)
Official title: A Phase 1/Phase 2 Study to Evaluate the Safety and Tolerability of MK-1088 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-05-27
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will evaluate the safety, tolerability, and pharmacokinetics (PK) of MK-1088 in monotherapy and in combination with pembrolizumab in participants with advanced solid tumors who have not responded to conventional therapy. The effect of MK-1088 on tumor size will also be examined.


Eligibility criteria: The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

* Has a histologically- or cytologically-confirmed diagnosis of advanced/metastatic solid tumor by pathology report and have received, have been intolerant to, or have been ineligible for treatment known to confer clinical benefit
* For metastatic castrate-resistant prostate cancer (mCRPC) only: (1) Must have previously received docetaxel, prior treatment with one other chemotherapy is allowed as well as up to 2 second-generation hormonal manipulations and (2) have prostate cancer progression within 6 months before screening, as determined by the investigator
* If human immunodeficiency virus (HIV) positive, has well-controlled HIV on anti-retroviral therapy (ART)

Exclusion Criteria:

* Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
* Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active infection requiring therapy
* Has a history of interstitial lung disease
* Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
* Has an active autoimmune disease that has required systemic treatment in the past 2 years
* Has concurrent active Hepatitis B and Hepatitis C virus infection
* Has HIV with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has not fully recovered from any effects of major surgery without significant detectable infection
* Has a history or current evidence of a gastrointestinal (GI) condition or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Health Association (NYHA) Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
* Has a corrected QT interval using Fridericia's Correction Formula (QTcF) \>470 msec
* Has history of an allogeneic stem cell transplant or a solid organ transplant.
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
* Has received prior radiotherapy within 2 weeks of start of study intervention, or had radiation-related toxicities requiring corticosteroids
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has a "superscan" bone scan

Primary outcomes:
measure: Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)
timeFrame: Up to 21 days
measure: Percentage of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to ~13 months
measure: Percentage of Participants Discontinuing Study Treatment Due to an AE
timeFrame: Up to ~10 months
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Curve (AUC) of MK-1088
timeFrame: Pre-dose and 1, 2, 4, and 8 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2 and Cycle 2 Day 2; Pre-dose on Cycle 3, Cycle 4 and every 4 cycles up to ~3.5 months. Each cycle = 21 days
measure: Maximum Plasma Concentration (Cmax) of MK-1088
timeFrame: Pre-dose and 1, 2, 4, and 8 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2 and Cycle 2 Day 2; Pre-dose on Cycle 3, Cycle 4 and every 4 cycles up to ~3.5 months. Each cycle = 21 days
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-Modified RECIST 1.1 as Assessed by Investigator
timeFrame: Up to ~13 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 0103)
state: Florida
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center ( Site 0102)
state: New York
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START) ( Site 0101)
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0201)
state: Ontario
city: Quebec
country: Canada
facility: Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 0500)
state: Hovedstaden
city: Copenhagen
country: Denmark
facility: Herlev and Gentofte Hospital ( Site 0501)
state: Hovedstaden
city: Odense
country: Denmark
facility: Odense Universitetshospital ( Site 0502)
state: Syddanmark
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology Division ( Site 0300)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center ( Site 0302)
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden-Medizin ( Site 0402)
state: Grisons
city: st.Gallen
country: Switzerland
facility: Cantonal Hospital St.Gallen ( Site 0403)
state: Sankt Gallen
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale Bellinzona e Valli ( Site 0400)
state: Ticino
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: