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 targets both EGFR with TGFβ. Based on preclinical data, this 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 study population in dose escalation (Part A) of single agent BCA101 consists of subjects with EGFR-driven advanced solid tumours refractory to standard of care or for whom no standard of care is available. Dose escalation (Part A) of combination BCA101 and pembrolizumab consists of subjects with either Squamous Cell Carcinoma of the Head and Neck (HNSCC) or Squamous Cell Carcinoma of the Anal Canal (SCCAC) whose tumours are refractory to standard of care or for whom no standard of care is available. Once the maximum tolerated dose (MTD) / recommended dose (RD) of single agent BCA101 is determined, the study will continue with expansion cohorts (Part B) with select tumour types. Planned expansion cohorts for single agent BCA101 include 1) PD-L1 negative, EGFR-amplified Squamous Cell Lung Cancer (SqCLC); 2) RAS wild-type, microsatellite stable Colorectal Carcinoma (RAS wt, MSS CRC); 3) EGFR-amplified Triple Negative Breast Cancer; and 4) any solid tumour with either a KRAS G12D or G13D mutation. Planned expansion cohorts for the combination of BCA101 and pembrolizumab include: 1) HNSCC and 2) SCCAC.

View this trial on ClinicalTrials.gov