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

Study Overview
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Brief Summary
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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

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 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.

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

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

Intervention / Treatment
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* Drug: MCLA-145


Participation Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MCLA-145<br>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<br>* full-length IgG1 bispecific antibody specifically targeting PD-L1 and CD137<br>* Other names: bispecific;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First-in-human, MCLA-145, Antibodies, Bispecific