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

• ClinicalTrials.gov Identifier: NCT03922204
• Recruitment Status: Recruiting
• First Posted: April 19, 2019
• Last Update Posted: May 27, 2022
• Sponsor: Merus N.V.
• Collaborator: Incyte Corporation
• Information provided by (Responsible Party): Merus N.V.

Study Description

Brief Summary:

This is a Phase 1, open label, non-randomised, dose-escalation single agent study with expansion cohorts for dose confirmation/safety and preliminary efficacy of MCLA-145 in advanced or metastatic malignancies

Condition or disease	Intervention/treatment	Phase
Advanced Cancer; Solid Tumor, Adult; B-cell Lymphoma, Adult	Drug: MCLA-145	Phase 1

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 for the expansion.

Part 2 is a dose expansion to confirm the dose of MCLA-145 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); and Follow-up ( 30 days and 90 days after the last dose) including survival follow-up checks every 2 months up to 12 months after the last dose.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 118 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label, Dose-Escalation, Safety, Tolerability, and Preliminary Efficacy Study of MCLA-145 in Participants With Advanced or Metastatic Malignancies
• Actual Study Start Date: May 8, 2019
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

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 ( every 2 weeks ) 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 at the recommended phase II dose every 2 weeks. The duration of each treatment cycle is 28 days

Drug: MCLA-145; full-length IgG1 bispecific antibody specifically targeting PD-L1 and CD137; Other Name: bispecific

Outcome Measures

Primary Outcome Measures :

1. Number of patients with Dose Limiting Toxicities [ Time Frame: first 28 days of treatment ]
2. Number of patients with Adverse Events and Serious Adverse Events [ Time Frame: up to 90 days post-last dose ]

Secondary Outcome Measures :

1. Overall response rate (ORR) [ Time Frame: Every 8 to 12 weeks until study ends, approximately 4 years ]
2. Duration of response ( DOR) [ Time Frame: Every 8 to 12 weeks until study ends, approximately 4 years ]
3. Disease control rate ( DCR) [ Time Frame: Every 8 to 12 weeks until study ends, approximately 4 years ]
4. Progression Free Survival ( PFS) [ Time Frame: Every 8 to 12 weeks until study ends, approximately 4 years ]
5. Incidence of anti-drug antibodies against MCLA-145 [ Time Frame: 12 months ]
6. Peak plasma concentration [Cmax] [ Time Frame: 12 months ]
7. Area under the plasma concentration versus time curve [AUC] [ Time Frame: 12 months ]
8. Half-life [t1/2] [ Time Frame: 12 months ]

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Contacts

Contact: Gianluca Laus, MD; +31850162500; enquires@merus.nl

Contact: Andrew Joe, MD; +31850162500; enquires@merus.nl

Locations

United States, California

Moores Cancer Centre; Recruiting

La Jolla, California, United States, 92093-0987

Contact: Sandip Patel, MD

Principal Investigator: Sandip Patel, MD

United States, Massachusetts

Dana-Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Stephen Hodi, MD

Principal Investigator: Stephen Hodi, MD

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

Contact: Chrisann Kyi, MD

Principal Investigator: Chrisann Kyi, MD

Belgium

University Hospital Antwerp; Recruiting

Antwerp, Edegem, Belgium, 2650

Contact: Hans Prenen, MD, Ph.D

Principal Investigator: Hans Prenen, MD, Ph.D

Universitair Ziekenhuis Gent; Recruiting

Gent, Belgium, 9000

Contact: Sylvie Rottey, MD

Principal Investigator: Sylvie Rottey, MD

Netherlands

Netherlands Cancer Institute; Recruiting

Amsterdam, Netherlands, 1066CX

Contact: Marloes Van Dongen, MD

Principal Investigator: Marloes Van Dongen, MD, Ph.D

Spain

Clinica Universidad de Navarra; Recruiting

Madrid, Spain, 28027

Contact: Ignacio Melero Bermejo, MD

Principal Investigator: Ingnacio Melero Bermejo, MD

Hospital Universitario Fundarcion Jimenez Diaz; Recruiting

Madrid, Spain, 28040 EP

Contact: Victor Moreno Garcia, MD

Principal Investigator: Victor Moreno Garcia, MD, Ph.D

Hospital Universitario Virgen de la Victoria; Recruiting

Málaga, Spain, 29010

Contact: Laura Medina Rodriguez, MD

Principal Investigator: Laura Medina Rodriguez, MD

Clinica Universidad de Navarra; Recruiting

Pamplona, Spain, 31008 EP

Contact: Ignacio Melero Bermejo, MD

Principal Investigator: Ignacio Melero Bermejo, MD

Sponsors and Collaborators

Merus N.V.

Incyte Corporation

Investigators

• Study Director: Gianluca Laus, MD; Merus N.V.

More Information

• Responsible Party: Merus N.V.
• ClinicalTrials.gov Identifier: NCT03922204
• Other Study ID Numbers: MCLA-145-CL01/MCLA-145-101; 2018-004396-13 ( EudraCT Number )
• First Posted: April 19, 2019
• Last Update Posted: May 27, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merus N.V.:

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