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

Advanced Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03922204
• Other study ID #: MCLA-145-CL01/MCLA-145-101
• Secondary ID: 2018-004396-13
• Status: Recruiting
• Phase: Phase 1
• Start date: May 8, 2019
• Est. completion date: December 2022

Study information

• Verified date: May 2022
• Source: Merus N.V.
• Contact: Gianluca Laus, MD
• Phone: +31850162500
• Email: enquires[@]merus.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 118
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Belgium	University Hospital Antwerp	Antwerp	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Netherlands	Netherlands Cancer Institute	Amsterdam
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital Universitario Fundarcion Jimenez Diaz	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Clinica Universidad de Navarra	Pamplona
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Moores Cancer Centre	La Jolla	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Merus N.V.	Incyte Corporation

Countries where clinical trial is conducted

United States,  Belgium,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with Dose Limiting Toxicities		first 28 days of treatment
Primary	Number of patients with Adverse Events and Serious Adverse Events		up to 90 days post-last dose
Secondary	Overall response rate (ORR)		Every 8 to 12 weeks until study ends, approximately 4 years
Secondary	Duration of response ( DOR)		Every 8 to 12 weeks until study ends, approximately 4 years
Secondary	Disease control rate ( DCR)		Every 8 to 12 weeks until study ends, approximately 4 years
Secondary	Progression Free Survival ( PFS)		Every 8 to 12 weeks until study ends, approximately 4 years
Secondary	Incidence of anti-drug antibodies against MCLA-145		12 months
Secondary	Peak plasma concentration [Cmax]		12 months
Secondary	Area under the plasma concentration versus time curve [AUC]		12 months
Secondary	Half-life [t1/2]		12 months