A Study of MK-1484 as Monotherapy and in Combination With Pembrolizumab (MK-3475) In Advanced or Metastatic Solid Tumors (MK-1484-001)

NCT05382325 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: 1484-001MK-1484-0012023-505067-362021-005220-38
• Study Type: interventional
• Target: 70
• Locations: 4 countries
• Sites: 8

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.

Conditions

Advanced or Metastatic Solid Tumors

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Outcome Measures

Primary Outcomes (3)

• Number of Participants with a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 5.0

  DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment: Grade (Gr) 4 nonhematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia: Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia associated with clinically significant bleeding; Gr 4 anemia regardless of duration; Nonhematologic AE Gr ≥3 in severity, with exceptions; Any Gr 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; Gr 3 or Gr 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-1484 dose during Cycle 1 resulting from treatment-related AE; Gr 5 toxicity.

  Cycle 1 (Up to 21 days)

• Number of Participants Who Experience At Least One AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported.

  Up to approximately 27 months

• Number of Participants Who Discontinue Study Treatment Due to an AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE will be reported.

  Up to approximately 24 months

Secondary Outcomes (3)

• Area Under the Curve (AUC) of MK-1484

  At designated time points (Up to approximately 24 months)

• Minimum Serum Concentration (Cmin) of MK-1484

  At designated time points (Up to approximately 24 months)

• Maximum Serum Concentration (Cmax) of MK-1484

  At designated time points (Up to approximately 24 months)

Study Arms (2)

MK-1484

EXPERIMENTAL

Participants will receive MK-1484 every 3 weeks (Q3W) or 21-day cycle at escalating dose levels from 0.2-60 mg for up to a total of 35 cycles (up to approximately 24 months).

Biological: MK-1484

MK-1484 + Pembrolizumab

EXPERIMENTAL

Participants will receive MK-1484 Q3W at escalating dose levels from 10-60 mg plus pembrolizumab 200 mg once every 21-day cycle for up to a total of 35 cycles (up to approximately 24 months).

Biological: MK-1484; Biological: Pembrolizumab

Interventions

MK-1484 BIOLOGICAL

Subcutaneous (SC) injection

Also known as: SP'482

MK-1484; MK-1484 + Pembrolizumab

Pembrolizumab BIOLOGICAL

Intravenous (IV) infusion

Also known as: MK-3475, Keytruda®

MK-1484 + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (8)

Sanford Cancer Center ( Site 0005)

Sioux Falls, South Dakota, 57104, United States

Location

NEXT Oncology ( Site 0001)

San Antonio, Texas, 78229, United States

Location

Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0011)

Toronto, Ontario, M5G 2M9, Canada

Location

Rambam Health Care Campus-Oncology ( Site 0021)

Haifa, 3109601, Israel

Location

Sheba Medical Center-ONCOLOGY ( Site 0020)

Ramat Gan, 5265601, Israel

Location

Nederlands Kanker Instituut - Antoni van Leeuwenhoek - NKI-AVL ( Site 0035)

Amsterdam, North Holland, 1066CX, Netherlands

Location

Erasmus Medisch Centrum-Medical Oncology ( Site 0036)

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 0037)

Utrecht, 3584 CX, Netherlands

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: May 19, 2022
• Study Start: June 16, 2022
• Primary Completion: July 31, 2026
• Study Completion: July 31, 2026
• Last Updated: November 14, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

IL (2); CA (1); US (2); NL (3)