Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors
First-in-Human, Phase 1/1b, Open-label, Multicenter Study of Bifunctional EGFR/TGFβ Fusion Protein BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-Driven Advanced Solid Tumors
2 other identifiers
interventional
292
3 countries
20
Brief 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 tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2020
Longer than P75 for phase_1
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2020
CompletedFirst Submitted
Initial submission to the registry
June 10, 2020
CompletedFirst Posted
Study publicly available on registry
June 12, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
August 15, 2025
August 1, 2025
6.6 years
June 10, 2020
August 14, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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 Outcomes (11)
Objective Response Rate
24 months
Clinical Benefit Rate
24 months
Progression free survival
24 months
Duration of Response
24 months
Overall Survival
24 months
- +6 more secondary outcomes
Study Arms (2)
BCA101 Monotherapy
EXPERIMENTALRoute: IV Infusion Frequency: QW Current Dose: 1500mg
BCA101 + pembrolizumab
EXPERIMENTALRoute: IV Infusion Frequency: Q3W Dose: 200mg
Interventions
EGFR/TGFβ fusion monoclonal antibody
Eligibility Criteria
You may qualify if:
- 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:
- PART B (Cohort expansion):
- Single agent BCA101 - patients with the following tumor type will be eligible:
- Expansion Cohort 1: Cutaneous Squamous Cell Carcinoma (CSCC) - i. patients must have received (or been intolerant to or ineligible for) prior anti-PD-1 therapy in the metastatic or locally advanced setting.
- ii. No prior history of treatment with anti-EGFR antibodies in the unresectable/metastatic setting (prior treatment with radiotherapy in the adjuvant setting is allowed).
- Combination BCA101 and pembrolizumab - patients with the following tumor types will be eligible:
- Expansion Cohort 2: Head and Neck Squamous Cell Carcinoma (HNSCC), metastatic or unresectable, recurrent with a Combined Positive Score (CPS) equal to or greater than 1, as determined by an CLIA-approved laboratory test. Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology).
- i. Patients must have no prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed \>6 months prior if given as part of multimodal treatment for locally advanced disease) or prior history of immune checkpoint inhibitors with the exception of neoadjuvant therapy (\>6 months prior to study drug initiation). No prior history of anti-EGFR antibodies (with the exception of radiosensitizing agents and multimodal treatment for locally advanced disease).
- ii. Patients must provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate is not sufficient): A newly obtained biopsy (within 90 days prior to start of study treatment) is preferred but an archival sample is acceptable.
- iii. Patients must have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer
- Expansion Cohort 3: Squamous Carcinoma of the Anal Canal (SCAC), locally advanced/unresectable or metastatic.
- i. Patients must have received (or been intolerant to or ineligible for) at least 1 prior line of chemotherapy and received no more than 2 prior lines of systemic treatments for treatment of unresectable and/or metastatic disease. No prior history of immune checkpoint inhibitors.
- +5 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bicara Therapeuticslead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (20)
Moores Cancer Center UC San Diego Health
La Jolla, California, 92093, United States
Keck School of Medicine of USC
Los Angeles, California, 90033, United States
UCLA
Los Angeles, California, 90095, United States
University of California, Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
H. Lee Moffitt Cancer Center and Research Institute, Inc
Tampa, Florida, 33612, United States
Dana Farber/Partners Cancer Care Inc
Boston, Massachusetts, 02115, United States
Memorial Sloan Kettering
New York, New York, 10017, United States
Columbia University Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Medical University of South Carolina, Hollings Cancer Center
Charleston, South Carolina, 29425, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050, Australia
Calvary Mater Newcastle
Waratah, New South Wales, 2298, Australia
Austin Hospital
Heidelberg, Victoria, 3084, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 10, 2020
First Posted
June 12, 2020
Study Start
June 1, 2020
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
June 1, 2027
Last Updated
August 15, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will not share