Clinical trial NCT05382325: A Study of MK-1484 as Monotherapy and in Combination With Pembrolizumab (MK-3475) In Advanced or Metastatic Solid Tumors (MK-1484-001)
Official title: A Phase 1, Open-Label, Multicenter Study to Assess the Safety and Tolerability of MK-1484 as a Monotherapy and in Combination With Pembrolizumab in Adult Participants With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-05-19
Enrollment: 70
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 purpose of this study is to assess the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of MK-1484 administered as monotherapy and in combination with pembrolizumab (MK-3475) in adults with advanced or metastatic solid tumors.


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

Inclusion Criteria:

* Has a 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.
* Has measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by the local site investigator/radiology.
* Has normal cardiac function based on transthoracic echocardiogram (TTE) or multigated acquisition scan (MUGA)
* Has provided an evaluable archival or newly obtained tumor tissue sample for biomarker analysis.
* Has adequate organ function.
* A male participant must agree to use contraception and should refrain from donating sperm during the specified period(s) of at least 120 days after study interventions.
* A female participant is eligible to participate if she is not pregnant or breastfeeding and at least 1 of the following: not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period for at least 120 days after study intervention.

Exclusion Criteria:

* Has and chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related AEs). Participants receiving ongoing replacement hormone therapy for endocrine immune-related AEs will not be excluded from participation in this study.
* 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 had a severe hypersensitivity reaction to treatment with a monoclonal antibody and/or components of the study interventions.
* Has an active infection requiring therapy.
* Has a history of interstitial lung disease.
* Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy.
* Participants with known human immunodeficiency virus (HIV) and/or hepatitis B or C infections, or known to be positive for hepatitis B surface antigen (HBsAg)/hepatitis B virus (HBV) DNA or hepatitis C Antibody or ribonucleic acid (RNA).
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, make administration of the study drugs hazardous, or make it difficult to monitor adverse effects such that it is not in the best interest of the participant to participate.
* Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the study.
* Has not fully recovered from any effects of major surgery without significant detectable infection. Surgeries that required general anesthesia must be completed at least 2 weeks before first study intervention administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study intervention administration and participants should be recovered.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the start of study treatment.
* Has had an allogeneic tissue/solid organ transplant in the last 5 years or has evidence of graft-versus-host disease.
* Has received any prior interleukin-2 (IL-2) based therapy.

Primary outcomes:
measure: Number of Participants with a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 5.0
timeFrame: Cycle 1 (Up to 21 days)
measure: Number of Participants Who Experience At Least One AE
timeFrame: Up to approximately 27 months
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Area Under the Curve (AUC) of MK-1484
timeFrame: At designated time points (Up to approximately 24 months)
measure: Minimum Serum Concentration (Cmin) of MK-1484
timeFrame: At designated time points (Up to approximately 24 months)
measure: Maximum Serum Concentration (Cmax) of MK-1484
timeFrame: At designated time points (Up to approximately 24 months)
Other outcomes:
Locations:
city: Sioux Falls
country: United States
facility: Sanford Cancer Center ( Site 0005)
state: South Dakota
city: San Antonio
country: United States
facility: NEXT Oncology ( Site 0001)
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0011)
state: Ontario
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology ( Site 0021)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-ONCOLOGY ( Site 0020)
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut - Antoni van Leeuwenhoek - NKI-AVL ( Site 0035)
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum-Medical Oncology ( Site 0036)
state: Zuid-Holland
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 0037)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: