Clinical trial NCT03922204: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Solid Tumor, Adult
B-cell Lymphoma, Adult
Keywords: First-in-human
MCLA-145
Antibodies
Bispecific
Lead sponsor: Merus N.V.
Sponsor class: INDUSTRY
First posted: 2019-04-19
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Number of patients with Dose Limiting Toxicities
timeFrame: first 28 days of treatment
measure: Number of patients with Adverse Events and Serious Adverse Events
timeFrame: up to 90 days post-last dose
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Every 8 to 12 weeks until study ends, approximately 4 years
measure: Duration of response ( DOR)
timeFrame: Every 8 to 12 weeks until study ends, approximately 4 years
measure: Disease control rate ( DCR)
timeFrame: Every 8 to 12 weeks until study ends, approximately 4 years
measure: Progression Free Survival ( PFS)
timeFrame: Every 8 to 12 weeks until study ends, approximately 4 years
measure: Incidence of anti-drug antibodies against MCLA-145
timeFrame: 12 months
measure: Peak plasma concentration [Cmax]
timeFrame: 12 months
measure: Area under the plasma concentration versus time curve [AUC]
timeFrame: 12 months
measure: Half-life [t1/2]
timeFrame: 12 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores Cancer Centre
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
state: Edegem
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Madrid
country: Spain
facility: Hospital Universitario Fundarcion Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
Study officials:
affiliation: Merus N.V.
name: Gianluca Laus, MD
role: STUDY_DIRECTOR
References: