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

  • End date
    Jun 1, 2024
  • participants needed
  • sponsor
    Bicara Therapeutics
Updated on 16 October 2022
ct scan
monoclonal antibodies
measurable disease
breast cancer
squamous cell carcinoma
lung cancer
investigational drug
experimental drug
primary tumor
chemotherapy regimen
gastric cancer
programmed cell death 1 ligand 1
cancer chemotherapy
solid tumour
solid tumor
advanced solid tumor
squamous cell carcinoma of head and neck
human papillomavirus
head and neck carcinoma
carcinoma of oropharynx


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.

Condition 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
Treatment Pembrolizumab, BCA101
Clinical Study IdentifierNCT04429542
SponsorBicara Therapeutics
Last Modified on16 October 2022


Yes No Not Sure

Inclusion Criteria

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)
i. Single agent BCA101 - patients with the following tumor type will be
• 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)
ii. 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

Exclusion Criteria

For Part A: Exposure to anti-EGFR antibodies within 4 weeks of the first dose of study
Pregnant or breastfeeding women
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
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
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