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Investigating BCA101 for advanced solid tumors driven by EGFR

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

PHASE1 · Bicara Therapeutics · NCT04429542

This study is testing a new treatment called BCA101 to see if it can help people with advanced solid tumors that are driven by EGFR, especially those who haven't responded to other therapies.

Quick facts

PhasePHASE1
Study typeInterventional
Enrollment292 (estimated)
Ages18 Years and up
SexAll
SponsorBicara Therapeutics (industry)
Drugs / interventionspembrolizumab, cetuximab, chemotherapy, prednisone
Locations20 sites (La Jolla, California and 19 other locations)
Trial IDNCT04429542 on ClinicalTrials.gov

What this trial studies

This Phase 1/1b clinical trial evaluates the safety and tolerability of BCA101, a first-in-class bifunctional antibody targeting both EGFR and TGFβ, in patients with advanced solid tumors that are EGFR-driven. The study includes a dose escalation phase for both single-agent BCA101 and its combination with pembrolizumab, focusing on patients whose tumors are refractory to standard treatments. Participants will undergo biopsies to assess tumor response and will be monitored for side effects throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include patients with EGFR-driven advanced solid tumors who have exhausted standard treatment options or for whom no standard care is available.

Not a fit: Patients with tumors that are not driven by EGFR or those who have not yet received standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced EGFR-driven solid tumors that currently have limited treatment options.

How similar studies have performed: Other studies have shown promise with similar approaches targeting EGFR and TGFβ, suggesting potential for success in this novel treatment strategy.

Eligibility criteria

Show full inclusion / exclusion criteria 
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):

1. 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).
2. 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.
   * 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.

   ii. Patients must have progressed on one prior systemic therapy in the metastatic setting.

   iii. No prior history of treatment with anti-EGFR antibodies in the metastatic setting.

   • Expansion Cohort 6: Head and Neck Squamous Cell Carcinoma (HNSCC), metastatic or unresectable, recurrent with a Combined Positive Score (CPS) less than 1, as determined by PD-L1 IHC 22C3 pharmDx.
3. Randomized to either ficerafusp alfa alone or in combination with pembrolizumab • Expansion Cohort 9: Colorectal cancer (CRC) i. Patients must have received at least 2 and no more than 3 prior lines of systemic therapy including two standard treatment regimens.

Exclusion Criteria:

* 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

Where this trial is running

La Jolla, California and 19 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: 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

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.