This is a Phase 1/2 open-label, multi-center, multi-national study with an initial dose escalation part to determine the recommended Phase II dose (RP2D) of MCLA-158 single agent in patients with mCRC.
The dose escalation part has been completed and the RP2D will be further evaluated in an expansion part of the study. Cohorts of selected solid tumor indications for which there is evidence of EGFR dependency and potential sensitivity to EGFR inhibition will be evaluated including head and neck cancer and metastatic colorectal cancer (mCRC).
The study will further assess the safety, tolerability, PK, PD, immunogenicity, and anti-tumor activity of MCLA-158 in monotherapy or in combination with other therapies.
Histologically or cytologically confirmed solid tumors with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent.
A baseline fresh tumor sample (FFPE) from a metastatic or primary site (if safe/feasible).
Amenable for biopsy (if safe/feasible).
Measurable disease as defined by RECIST version 1.1 by radiologic methods.
Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 14 days of study entry.
Known leptomeningeal involvement.
Participation in another clinical study or treatment with any investigational drug within 4 weeks prior to study entry.
Any systemic anticancer therapy within 4 weeks or 5 half-lives whichever is shorter of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity ( e.g. mitomycin C,nitrosoureas), or anticancer immunotherapies, a washout period of 6 weeks is required.
Parallel
MCLA-158
Drugfull-length IgG1 bispecific antibody targeting EGFR and LGR5
MCLA-158 + Pembrolizumab
Combination productMCLA-158 in combination with pembrolizumab will be explored first in HNSCC patients eligible to receive pembrolizumab as first-line monotherapy.
MCLA-158 + FOLFIRI
Combination productMCLA-158 in combination with FOLFIRI will be explored in mCRC patients with up to 1 line of prior regimen.
MCLA-158 + FOLFOX
Combination productMCLA-158 in combination with FOLFOX will be explored in mCRC patients with up to 1 line of prior regimen.
Escalation: Number of patients with Dose Limiting Toxicities (DLTs) during Cycle 1
Evaluation of the number and severity of participants with treatment related toxicities observed during the dose escalation.
Expansion (Single agent - randomized expansion in 2/3L Head and Neck cancer, and combination cohorts): Safety and tolerability: AEs and SAEs
Incidence, severity, and relationship of AEs and SAEs
Expansion (Single agent - randomized expansion in 2/3L Head and Neck cancer): Treatment discontinuations and dose modifications due to AEs
Treatment discontinuations due to AEs and dose modifications due to AEs
Expansion (single agent - randomized expansion in 2/3L Head and Neck cancer): Best overall response (BOR)
Evaluation of clinical benefit assessed by RECIST v1.1 determining Best overall response (BOR)
Escalation & Expansion: (mCRC subcutaneous cohort): Best Overall Response (BOR)
Evaluation of clinical benefit assessed by RECIST v1.1 determining Best overall response (BOR)
Expansion: Duration of response (DOR)
Evaluation of clinical benefit assessed by RECIST v1.1 determining duration of response (DOR)
Expansion: Progression Free Survival (PFS)
Evaluation of clinical benefit assessed by RECIST v1.1 determining progression free survival (PFS)
Expansion (mCRC combination cohorts): Progression Free Survival (PFS) rate at 4 months
Evaluation of clinical benefit assessed by RECIST v1.1 determining progression free survival (PFS) rate at 4 months
