Study of Safety and Tolerability of BCA101 Alone and in Combination With Pembrolizumab in Patients With EGFR-driven Advanced Solid Tumours

Official Title

First-in-Human, Phase 1/1b, Open-label, Multicentre Study of Bifunctional EGFR/TGFβ Fusion Protein BCA101 Alone and in Combination With Pembrolizumab in Patients With EGFR-Driven Advanced Solid Tumours

Summary:

The investigational drug to be studied in this protocol, BCA101, is a first-in-class compound that combines EGFR with TGFβ. Based on preclinical data, this dual targeted, bifunctional antibody may exert synergistic activity in patients with EGFR-driven tumours.

Trial Description

Primary Outcome:

• Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs
• Tolerability of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs
• Incidence of Dose Limiting Toxicities (DLTs)

Secondary Outcome:

• Objective Response Rate
• Clinical Benefit Rate
• Progression free survival
• Duration of Response
• Overall Survival
• AUC of BCA101 and pembrolizumab
• Cmax of BCA101 and pembrolizumab
• Tmax of BCA101 and pembrolizumab
• Concentration vs time profile of BCA101 and pembrolizumab
• Half-life of BCA101 and pembrolizumab
• Immunogenicity of BCA101 and pembrolizumab

This is a Phase 1/1b, open-label study, which consists of dose escalation parts (Part A) followed by expansion cohorts (Part B) for both single agent BCA101 and combination BCA101 plus pembrolizumab. The first dose escalation part will be conducted with single agent BCA101 in subjects with advanced EGFR-driven advanced solid tumours. The study population in Part A consists of subjects with EGFR-driven advanced solid tumours who are refractory to standard of care or for whom standard of care is not available. Targeting both the EGFR and TGFβ pathways may provide synergistic activity in these patients. This dose-finding part of the study will lead to selected subject population in Part B of the study. Once the maximum tolerated dose (MTD) / recommended dose (RD) of single agent BCA101 is determined, the study will continue with expansion cohorts with select tumour types. Part A consists of another dose escalation part of BCA101 and pembrolizumab in head and neck squamous cell carcinoma and squamous cell carcinoma of the anal canal, followed by an expansion part. Part B (cohort expansion) will begin enrolling subjects once the corresponding arm has established an RD. Planned expansion cohorts for single agent BCA101 include 1) PD-L1 negative, EGFR-amplified squamous cell cancer of the lung; 2) RAS wild-type, microsatellite stable colorectal carcinoma; 3) EGFR-amplified triple negative breast cancer; and 4) any solid tumour with a KRAS G12D or G13D mutation. Planned expansion cohorts for the combination of BCA101 and pembrolizumab include: 1) head and neck squamous cell carcinoma and 2) squamous cell carcinoma of the anal canal.

View this trial on ClinicalTrials.gov