Study of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors (MK-4464-001)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 1

Conditions: Neoplasms; Advanced/Metastatic Solid Tumors

Treatments: Biological: MK-4464; Drug: 89Zr-MK-4464; Biological: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05514444

2021-005882-42 (EudraCT Number)

4464-001

MK-4464-001 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of MK-4464 as monotherapy and in combination with pembrolizumab in participants with advanced/metastatic solid tumors.

Enrollment: 260 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

The key Inclusion Criteria include but are not limited to the following:

• Have a histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit
• Must submit a baseline tumor sample for analysis
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART)
• Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before randomization.

Exclusion criteria

The key Exclusion Criteria include but are not limited to the following:

• Has had 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 CTCAE Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
• 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
• History of an allogenic stem cell transplant or a solid organ transplant
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• 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
• Has received radiation therapy to the lung that is >30 gray (Gy) within 6 months of the first dose of study treatment
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 28 days

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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260 participants in 3 patient groups

MK-4464

Experimental group

Description:

Participants will receive an intravenous (IV) infusion of MK-4464 administered in escalating doses every 3 weeks for up to 35 cycles. Escalation to subsequent MK-4464 doses will be based on safety of previous dose.

Treatment:

Biological: MK-4464

MK-4464 + Pembrolizumab

Experimental group

Description:

Participants will receive an IV infusion of MK-4464 administered in escalating doses and a 200 mg IV infusion of Pembrolizumab every 3 weeks for up to 35 cycles. Escalation to subsequent MK-4464 doses will be based on safety of MK-4464 monotherapy arm.

Treatment:

Biological: Pembrolizumab

Biological: MK-4464

MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464

Experimental group

Description:

Participants will receive an IV infusion of 89Zr-MK-4464 + IV infusion of MK-4464 on Cycle 1 Day 1, followed by an IV infusion of MK-4464 + a 200 mg IV infusion of pembrolizumab starting on Cycle 2 Day 1 and every 3 weeks for up to 35 cycles. Each cycle=3 weeks. MK-4464 doses will be based on safety of MK-4464 monotherapy arm. Participants may receive a 200 mg IV infusion of pembrolizumab on cycle 36.

Treatment:

Drug: 89Zr-MK-4464

Biological: Pembrolizumab

Biological: MK-4464