Study Of Safety And Tolerability Of BCA101 Monotherapy And In Combination Therapy In Patients With EGFR-driven Advanced Solid Tumors

Study Overview

Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors

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 tumors.

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 tumors 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 tumors 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 tumor types. Expansion cohorts for single agent BCA101 will include cutaneous squamous cell carcinoma. Planned expansion cohorts for the combination of BCA101 and pembrolizumab include: 1) HNSCC and 2) SCCAC.

Head and Neck Squamous Cell Carcinoma
Squamous Cell Carcinoma of Anal Canal
Colorectal Cancer
Squamous Cell Carcinoma of the Lung
EGFR Amplification
Epithelial Ovarian Cancer
Pancreas Cancer
Cutaneous Squamous Cell Carcinoma
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck

DRUG: BCA101
DRUG: Pembrolizumab

BCA101X1101
KEYNOTE-E28 (OTHER Identifier) (OTHER: Merck Sharp & Dohme LLC)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2020-06-10	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-01-23
First Submitted that Met QC Criteria 2020-06-11	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-01-27
First Posted (ACTUAL) 2020-06-12	Results First Posted N/A	Last Verified 2025-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: BCA101 Monotherapy Route: IV Infusion Frequency: QW Current Dose: 1500mg	DRUG: BCA101 EGFR/TGFβ fusion monoclonal antibody
EXPERIMENTAL: BCA101 + pembrolizumab Route: IV Infusion Frequency: Q3W Dose: 200mg	DRUG: BCA101 EGFR/TGFβ fusion monoclonal antibody DRUG: Pembrolizumab anti-PD-1

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: BCA101 Monotherapy

Route: IV Infusion Frequency: QW Current Dose: 1500mg

DRUG: BCA101

EGFR/TGFβ fusion monoclonal antibody

EXPERIMENTAL: BCA101 + pembrolizumab

Route: IV Infusion Frequency: Q3W Dose: 200mg

DRUG: BCA101

EGFR/TGFβ fusion monoclonal antibody

DRUG: Pembrolizumab

anti-PD-1

Primary Outcome Measures	Measure Description	Time Frame
Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs	Incidence and severity of AEs and SAEs	24 months
Tolerability of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs	Incidence and severity of AEs and SAEs	24 months
Incidence of Dose Limiting Toxicities (DLTs)	Incidence of DLTs during the first cycle of treatment with BCA101 monotherapy or the combination of BCA101 and pembrolizumab.	21 days

Secondary Outcome Measures	Measure Description	Time Frame
Objective Response Rate	Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST	24 months
Clinical Benefit Rate	Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST	24 months
Progression free survival	Determine PFS in each part of the study, per RECIST v1.1 and iRECIST	24 months
Duration of Response	Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST	24 months
Overall Survival	Determine survival rates in each part of the study.	24 months
AUC of BCA101 and pembrolizumab	AUC	24 months
Cmax of BCA101 and pembrolizumab	Cmax	24 months
Tmax of BCA101 and pembrolizumab	Tmax	24 months
Concentration vs time profile of BCA101 and pembrolizumab	Ctrough	24 months
Half-life of BCA101 and pembrolizumab	Half-life	24 months
Immunogenicity of BCA101 and pembrolizumab	Incidence and titer of anti-drug-antibodies	24 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: David Bohr

Phone Number: 6178000335

Email: info@bicara.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patient must have measurable disease amendable to biopsy and be willing to undergo both a pre-treatment and on-treatment biopsy, as well as provide archival tumor if available from the primary tumor (a paraffin embedded tumor tissue block sufficient to obtain at least 10 sections of 4 to 5 micrometer thickness).
Patient must have a performance status of ≤1 on the Eastern Cooperative Oncology Group Performance Scale.
Patients must have evaluable or measurable disease (computed tomography [CT]/magnetic resonance imaging [MRI] scans performed within 21 days before the screening visit are acceptable) demonstrating measurable disease, i.e., at least 1 unidimensional measurable lesion as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) and Immune Response Evaluation Criteria in Solid Tumors (iRECIST).
Tumor eligibility:

Expansion Cohort 3: Squamous Carcinoma of the Anal Canal (SCAC), locally advanced/unresectable or metastatic.

Expansion Cohort 5: Squamous Non-Small Cell Lung Cancer (SqNSCLC) i. Patients must have a histologically or cytologically confirmed diagnosis of stage IV (AJCC 8th edition) squamous NSCLC. Patients with mixed histology (e.g., adenosquamous) are not allowed.

For Part A: Exposure to anti-EGFR antibodies within 4 weeks of the first dose of study drug.
Prior treatment with any anti-TGFβ therapy.
Prior history of Grade ≥ 2 intolerance or hypersensitivity reaction to cetuximab or other anti-EGFR therapy or other murine proteins or prior discontinuation of therapy in the setting of toxicity related to treatment.
Pregnant or breastfeeding women.
Any condition requiring systemic treatment with either corticosteroids (>10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days prior to the first dose of study drug, with the exception of topical, intranasal, intrabronchial, or ocular steroids.
Known history of a hematologic malignancy (or solid tumor other than the ones indicated for this study), unless the patient has undergone potentially curative therapy with no evidence of that disease for 2 years. Does not include tumors with a negligible risk of metastasis or death (e.g. adequately treated basal or squamous cell carcinoma, stage 1 prostate cancer, or carcinoma in situ of the cervix or carcinoma in situ of the breast). Subjects enrolling in the CSCC cohort may have chronic lymphocytic leukemia as long as the patient is not on active treatment.
Known cases of human immunodeficiency virus (HIV) are excluded if patients have a CD4+ T-cell (CD4+) count <250 cells/uL. To ensure that effective antiretroviral therapy (ART) is tolerated and that toxicities are not confused with investigational drug toxicities, trial participants should be on established ART for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
Patients with chronic HBV infection with active disease who meet the criteria for anti-HBV therapy and are not on a suppressive antiviral therapy prior to initiation of study treatment
Patients with a known history of hepatitis C who have not completed curative antiviral treatment or have a HCV viral load above the limit of quantification

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Merck Sharp & Dohme LLC

Investigators

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