A Study of Bispecific Antibody MCLA-145 in Patients with Advanced or Metastatic Malignancies

Merus

Status and phase: Active, not recruiting; Phase 1

Conditions: Advanced Cancer; Solid Tumor, Adult; B-cell Lymphoma, Adult

Treatments: Drug: MCLA-145; Drug: Pembrolizumab (Keytruda)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03922204

MCLA-145-CL01/MCLA-145-101

2018-004396-13 (EudraCT Number)

Details and patient eligibility

About

This is an open-label, non-randomized, Phase 1 study to determine the safety, tolerability, and preliminary efficacy of MCLA-145 in adult patients with advanced metastatic solid tumors or B-cell lymphomas. The study will be conducted in 2 parts.

Full description

Study Design: This open label, multicenter, first in human study consists of 2 parts. Part 1 is a dose escalation to find the recommended dose of MCLA-145 in monotherapy or in combination with pembrolizumab.

Part 2 is a dose expansion to confirm the dose of MCLA-145, alone or in combination through further evaluation of safety, tolerability, Pk, preliminary antitumor activity, and functional target engagement.

The study includes three periods: Screening (up to 28 days prior to the first dose of study drug); Treatment (first dose of study drug with treatment cycles of 28 days for patients treated Q2W and 21 days for patients treated Q3W); Safety Follow-up (30 and 90 days after the last dose) including survival follow-up checks every 2 months up to 12 months after the last dose.

Enrollment: 238 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed advanced or recurrent/metastatic solid tumors or B-cell lymphomas, that are considered non-amenable to surgery or other curative treatments or procedures (if applicable)
• Measureable disease per RECIST v1.1 or Lugano Criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Received prior standard therapy for advanced or recurrent/metastatic disease as applicable to tumor type
• Received a maximum of 4 prior systemic treatment regimens (inclusive of chemotherapy, immunotherapy, and targeted therapy regimens) for advanced or recurrent/metastatic disease
• Life expectancy of ≥12 weeks, as per investigator judgement

Exclusion criteria

• The following B-cell neoplasms: Burkitt lymphoma, lymphoblastic leukemia/lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia
• Prior therapy containing an anti-PD-L1 agent or T-cell agonist
• Current serious illness or medical condition including, but not limited to uncontrolled active infection
• Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting MCLA-145
• Prior ≥ Grade 3 immune-mediated AEs with anti-PD-1 therapy
• History of any grade immune-mediated ocular AEs.
• Known hypersensitivity or severe reaction to any component of MCLA-145 or formulation components
• Participants who have active or inactive autoimmune disease or syndrome (eg, rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) that has required systemic treatment in the past 2 years or who are receiving systemic therapy for an autoimmune or inflammatory disease (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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238 participants in 2 patient groups

MCLA-145

Experimental group

Description:

In Part 1, the dose escalation phase, patients with advanced or recurrent/metastatic solid tumors or B-cell lymphomas will receive escalating doses of MCLA-145 (either Q2W for those patients in treatment at the time of Amendment #4 or Q3W with Amendment #4 approval). Treatment will be with MCLA-145 (monotherapy) for Group A, or in combination with pembrolizumab for Group B, until MTD or RDE is reached. In Part 2, the expansion phase, participants with advanced or metastatic solid tumors will receive intravenous infusion of MCLA-145 either in monotherapy (Group A) or in combination with pembrolizumab (Group B) at the recommended phase II dose every 3 weeks. The duration of each treatment cycle is 21 days

Treatment:

Drug: MCLA-145

Group B Combination Treatment

Experimental group

Description:

Patients in Group B will be treated with MCLA-145 in Combination with pembrolizumab 200mg Q3W.

Treatment:

Drug: Pembrolizumab (Keytruda)

Drug: MCLA-145