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

NCT03922204 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: MCLA-145-CL01/MCLA-145-1012018-004396-13
• Study Type: interventional
• Target: 72
• Locations: 4 countries
• Sites: 8

Brief Summary

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.

Conditions

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

Keywords

First-in-human; MCLA-145; Antibodies; Bispecific

Outcome Measures

Primary Outcomes (2)

• Number of patients with Dose Limiting Toxicities

  first 28 days of treatment

• Number of patients with Adverse Events and Serious Adverse Events

  up to 90 days post-last dose

Secondary Outcomes (8)

• Overall response rate (ORR)

  Every 8 to 12 weeks until study ends, approximately 4 years

• Duration of response ( DOR)

  Every 8 to 12 weeks until study ends, approximately 4 years

• Disease control rate ( DCR)

  Every 8 to 12 weeks until study ends, approximately 4 years

• Progression Free Survival ( PFS)

  Every 8 to 12 weeks until study ends, approximately 4 years

• Incidence of anti-drug antibodies against MCLA-145

  12 months

Study Arms (2)

MCLA-145

EXPERIMENTAL

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

Drug: MCLA-145

Group B Combination Treatment

EXPERIMENTAL

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

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

Interventions

MCLA-145 DRUG

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

Also known as: bispecific

Group B Combination Treatment; MCLA-145

Pembrolizumab (Keytruda) DRUG

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

Group B Combination Treatment

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merus B.V.: lead

Study Sites (8)

Moores Cancer Centre

La Jolla, California, 92093-0987, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University Hospital Antwerp

Antwerp, Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Netherlands Cancer Institute

Amsterdam, 1066CX, Netherlands

Location

Hospital Universitario Fundarcion Jimenez Diaz

Madrid, 28040 EP, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008 EP, Spain

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Gianluca Laus, MD

  Merus B.V.

  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: April 15, 2019
• First Posted: April 19, 2019
• Study Start: May 8, 2019
• Primary Completion: November 7, 2024
• Study Completion: November 7, 2024
• Last Updated: December 11, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); ES (2); NL (1); BE (2)