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

NCT ID: NCT03922204

Last Updated: 2024-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-08

Study Completion Date

2024-11-07

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Advanced Cancer Solid Tumor, Adult B-cell Lymphoma, Adult

Keywords

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First-in-human MCLA-145 Antibodies Bispecific

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MCLA-145

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

Group Type EXPERIMENTAL

MCLA-145

Intervention Type DRUG

full-length IgG1 bispecific antibody specifically targeting PD-L1 and CD137

Group B Combination Treatment

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

Group Type EXPERIMENTAL

MCLA-145

Intervention Type DRUG

full-length IgG1 bispecific antibody specifically targeting PD-L1 and CD137

Pembrolizumab (Keytruda)

Intervention Type DRUG

Group B patients will be treated in combination with MCLA-145 and pembrolizumab 200mg Q3W.

Interventions

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MCLA-145

full-length IgG1 bispecific antibody specifically targeting PD-L1 and CD137

Intervention Type DRUG

Pembrolizumab (Keytruda)

Group B patients will be treated in combination with MCLA-145 and pembrolizumab 200mg Q3W.

Intervention Type DRUG

Other Intervention Names

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bispecific

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merus N.V.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gianluca Laus, MD

Role: STUDY_DIRECTOR

Merus N.V.

Locations

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Moores Cancer Centre

La Jolla, California, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University Hospital Antwerp

Antwerp, Edegem, Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

Netherlands Cancer Institute

Amsterdam, , Netherlands

Site Status

Hospital Universitario Fundarcion Jimenez Diaz

Madrid, , Spain

Site Status

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status

Countries

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United States Belgium Netherlands Spain

Other Identifiers

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2018-004396-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MCLA-145-CL01/MCLA-145-101

Identifier Type: -

Identifier Source: org_study_id