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

A Phase 1, Open-Label, Dose-Escalation, Safety, Tolerability, and Preliminary Efficacy Study of MCLA-145 in Participants With Advanced or Metastatic Malignancies

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.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer; Solid Tumor, Adult; B-cell Lymphoma, Adult
• Intervention / Treatment: Drug: MCLA-145; Drug: Pembrolizumab (Keytruda)

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Edegem
    • Antwerp, Edegem, Belgium, 2650
      • University Hospital Antwerp
• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Netherlands Cancer Institute
• Spain
  • Madrid, Spain, 28040 EP
    • Hospital Universitario Fundarcion Jimenez Diaz
  • Pamplona, Spain, 31008 EP
    • Clinica Universidad de Navarra
• United States
  • California
    • La Jolla, California, United States, 92093-0987
      • Moores Cancer Centre
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: MCLA-145; full-length IgG1 bispecific antibody specifically targeting PD-L1 and CD137; Other Names: bispecific
Experimental: Group B Combination Treatment; Patients in Group B will be treated with MCLA-145 in Combination with pembrolizumab 200mg Q3W.	Drug: MCLA-145; full-length IgG1 bispecific antibody specifically targeting PD-L1 and CD137; Other Names: bispecific; Drug: Pembrolizumab (Keytruda); Group B patients will be treated in combination with MCLA-145 and pembrolizumab 200mg Q3W.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Peak plasma concentration [Cmax]	12 months
Area under the plasma concentration versus time curve [AUC]	12 months
Half-life [t1/2]	12 months

Collaborators and Investigators

• Sponsor: Merus N.V.
• Collaborators: Incyte Corporation
• Investigators: Study Director: Gianluca Laus, MD, Merus N.V.

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2019
• Primary Completion (Actual): November 7, 2024
• Study Completion (Actual): November 7, 2024

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 18, 2019
• First Posted (Actual): April 19, 2019

Study Record Updates

• Last Update Posted (Actual): December 11, 2024
• Last Update Submitted That Met QC Criteria: December 6, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Antibodies; First-in-human; MCLA-145; Bispecific
• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: MCLA-145-CL01/MCLA-145-101; 2018-004396-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No