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

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.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Neoplasms; Carcinoma, Squamous Cell; Colorectal Cancer; Squamous Cell Carcinoma of Head and Neck; Epithelial Ovarian Cancer; Head and Neck Squamous Cell Carcinoma; Pancreas Cancer; Squamous Cell Carcinoma of the Lung; Cutaneous Squamous Cell Carcinoma; Squamous Cell Carcinoma of Anal Canal; EGFR Amplification
• Intervention / Treatment: Drug: BCA101; Drug: Pembrolizumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 292
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: David Bohr; Phone Number: 6178000335; Email: info@bicara.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris O'Brien Lifehouse
      • Contact: Jenny Lee, MBBS, FRACP
      • Principal Investigator: Jenny Lee, MBBS, FRACP
    • Waratah, New South Wales, Australia, 2298
      • Recruiting
      • Calvary Mater Newcastle
      • Contact: Phone Number: +61 2 40143590
      • Principal Investigator: Fiona Day
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Hospital
      • Contact: Alesha Thai, MBBS, FRACP, PhD; Phone Number: +61394965000
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter Maccallum Cancer Centre
      • Contact: Phone Number: +61 3 8559 5000
      • Principal Investigator: Danny Rischin, MD
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre
      • Contact: Phone Number: 18007110500
      • Principal Investigator: Phillippe Bedard, MD
• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • Moores Cancer Center UC San Diego Health
      • Principal Investigator: Assuntina Sacco, MD
      • Contact: Debanjali Ghosh; Phone Number: 858.246.0357; Email: d1ghosh@health.ucsd.edu
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA
      • Principal Investigator: Deborah Wong, MD
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Keck School of Medicine of USC
      • Principal Investigator: Gino In, MD
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California, Davis Comprehensive Cancer Center
      • Contact: Andrew Birkeland, MD
      • Principal Investigator: Andrew Birkeland, MD
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • H. Lee Moffitt Cancer Center and Research Institute, Inc
      • Principal Investigator: Christine Chung, MD
      • Contact: Hamza Elmohd; Phone Number: (813)-745-5554; Email: Hamza.elmohd@moffitt.org
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana Farber/Partners Cancer Care Inc
      • Principal Investigator: Glenn Hanna, MD
      • Contact: DFCI Clinical Trials Hotline; Phone Number: 8773387425
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Herbert Irving Comprehensive Cancer Center
      • Principal Investigator: Catherine Shu, MD
      • Contact: CPDM Nurse Navigator; Phone Number: 2123425162; Email: cancerclinicaltrials@cumc.columbia.edu
    • New York, New York, United States, 10017
      • Recruiting
      • Memorial Sloan Kettering
      • Contact: Phone Number: 646-608-3759
      • Principal Investigator: Paul Paik, MD
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
      • Contact: Daniel R Carrizosa, MD, MS, FACP; Phone Number: 980-442-3213
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Principal Investigator: Tamara Sussman, MD
      • Contact: Phone Number: (866) 223-8100; Email: TaussigResearch@ccf.org
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • UPMC Hillman Cancer Center
      • Contact: Sarah Brodeur; Email: brodeurs@upmc.edu
      • Principal Investigator: Dan Zanberg, MD
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
      • Principal Investigator: Ariel Birnbaum, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina, Hollings Cancer Center
      • Contact: Carly Fecio; Phone Number: 8437923479; Email: fecio@musc.edu
      • Principal Investigator: John Kaczmar, MD
      • Contact: Lilli Neal; Phone Number: 8437928113; Email: nealli@musc.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: Jennifer Choe, MD, PhD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Principal Investigator: Van Morris, MD
      • Contact: Beryl Tross; Phone Number: 7137450774; Email: bmtross@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

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; Other Names: Ficerafusp alfa
Experimental: BCA101 + pembrolizumab; Route: IV Infusion Frequency: Q3W Dose: 200mg	Drug: BCA101; EGFR/TGFβ fusion monoclonal antibody; Other Names: Ficerafusp alfa; Drug: Pembrolizumab; anti-PD-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bicara Therapeutics
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Estimated): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 14, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: EGFR; pembrolizumab; TGFβ; ficerafusp alfa
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Neoplasms, Squamous Cell; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Lung Neoplasms; Carcinoma, Squamous Cell; Pancreatic Neoplasms; Head and Neck Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: BCA101X1101; KEYNOTE-E28 (Other Identifier: Merck Sharp & Dohme LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No