Description:
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
Title
- Brief Title: A Study of Bispecific Antibody MCLA-145 in Patients With Advanced or Metastatic Malignancies
- 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 IDs
- ORG STUDY ID:
MCLA-145-CL01/MCLA-145-101
- SECONDARY ID:
2018-004396-13
- NCT ID:
NCT03922204
Conditions
- Advanced Cancer
- Solid Tumor, Adult
- B-cell Lymphoma, Adult
Interventions
Drug | Synonyms | Arms |
---|
MCLA-145 | bispecific | MCLA-145 |
Purpose
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
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.
Trial Arms
Name | Type | Description | Interventions |
---|
MCLA-145 | Experimental | 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 | |
Eligibility 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)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of patients with Dose Limiting Toxicities |
Time Frame: | first 28 days of treatment |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Overall response rate (ORR) |
Time Frame: | Every 8 to 12 weeks until study ends, approximately 4 years |
Safety Issue: | |
Description: | |
Measure: | Duration of response ( DOR) |
Time Frame: | Every 8 to 12 weeks until study ends, approximately 4 years |
Safety Issue: | |
Description: | |
Measure: | Disease control rate ( DCR) |
Time Frame: | Every 8 to 12 weeks until study ends, approximately 4 years |
Safety Issue: | |
Description: | |
Measure: | Progression Free Survival ( PFS) |
Time Frame: | Every 8 to 12 weeks until study ends, approximately 4 years |
Safety Issue: | |
Description: | |
Measure: | Incidence of anti-drug antibodies against MCLA-145 |
Time Frame: | 12 months |
Safety Issue: | |
Description: | |
Measure: | Peak plasma concentration [Cmax] |
Time Frame: | 12 months |
Safety Issue: | |
Description: | |
Measure: | Area under the plasma concentration versus time curve [AUC] |
Time Frame: | 12 months |
Safety Issue: | |
Description: | |
Measure: | Half-life [t1/2] |
Time Frame: | 12 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Merus N.V. |
Trial Keywords
- First-in-human
- MCLA-145
- Antibodies
- Bispecific
Last Updated
December 3, 2020