Advanced Cancer, B-cell Lymphoma, Adult, Solid Tumor, Adult
Conditions
Keywords
First-in-human, MCLA-145, Antibodies, Bispecific
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.
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.
Interventions
DRUGMCLA-145
full-length IgG1 bispecific antibody specifically targeting PD-L1 and CD137
Group B patients will be treated in combination with MCLA-145 and pembrolizumab 200mg Q3W.
Sponsors
Merus N.V.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Overall response rate (ORR) | Every 8 to 12 weeks until study ends, approximately 4 years |
| Area under the plasma concentration versus time curve [AUC] | 12 months |
| Half-life [t1/2] | 12 months |
| Peak plasma concentration [Cmax] | 12 months |
| Duration of response ( DOR) | Every 8 to 12 weeks until study ends, approximately 4 years |
Countries
Belgium, Netherlands, Spain, United States
Outcome results
None listed