Head and Neck Squamous Cell CarcinomaPhase 1NCT04429542
Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors
A Phase 1 study testing BCA101 and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma and Squamous Cell Carcinoma of Anal Canal, run by Bicara Therapeutics at 21 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma, Squamous Cell Carcinoma of Anal Canal, Colorectal Cancer
- What is being tested?
- BCA101 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 473 participants
- Where
- 21 sitesin 3 countries
- Study dates
- 1 Jun 2020to 30 Mar 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
- 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).
- 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).
- 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.
- 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.
- 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.
- Patients must have progressed on one prior systemic therapy in the metastatic setting.
- 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.
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
21 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 3 countries
United States15 sites, 15 recruiting
- Recruiting
Dana Farber/Partners Cancer Care Inc
Boston, Massachusetts, 02115
DFCI Clinical Trials Hotline, 877-338-7425
Michael Dennis, MD
- Recruiting
Medical University of South Carolina, Hollings Cancer Center
Charleston, South Carolina, 29425
843-792-9300, nealli@musc.edu
Carly Fecio, 8437923479, fecio@musc.edu
- Recruiting
Levine Cancer Institute
Charlotte, North Carolina, 28204
980-442-3213
Daniel Carrizosa, MD
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
866-223-8100, TaussigResearch@ccf.org
Tamara Sussman, MD
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Beryl Tross, 713-745-0774, bmtross@mdanderson.org
Van Morris, MD
- Recruiting
Moores Cancer Center UC San Diego Health
La Jolla, California, 92093
Moores UCSD Cancer Center Clinical Trials Office, 858-822-5354, d1ghosh@health.ucsd.edu
Assuntina Sacco, MD
- Recruiting
Keck School of Medicine of USC
Los Angeles, California, 90033
Clinical Trials Office, 323-442-1900
Gino In, MD
- Recruiting
UCLA
Los Angeles, California, 90095
UCLA Clinical Trials Office, 310-794-8783
Deborah Wong, MD
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Vanderbilt Clinical Research Center, 615-322-2312
Jennifer Choe, MD, PhD
- Recruiting
Memorial Sloan Kettering
New York, New York, 10017
646-608-3759
Eric Sherman, MD
- Recruiting
Columbia University Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
CPDM Nurse Navigator, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
Catherine Shu, MD
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Clinical Trials Office, 412-755-2930, brodeurs@upmc.edu
Dan Zanberg, MD
- Recruiting
Rhode Island Hospital
Providence, Rhode Island, 02903
Brown Health Clinical Trials Office, 401-444-5113
Ariel Birnbaum, MD
- Recruiting
University of California, Davis Comprehensive Cancer Center
Sacramento, California, 95817
Clinical Trials Office, 916-703-9184
Andrew Birkeland, MD
- Recruiting
H. Lee Moffitt Cancer Center and Research Institute, Inc
Tampa, Florida, 33612
Clinical Trials Office, 813-945-3563
Christine Chung, MD
Australia4 sites, 4 recruiting
- Recruiting
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
(02) 8514 0000
Jenny Lee, MBBS, FRACP
- Recruiting
Austin Hospital
Heidelberg, Victoria, 3084
+61394965000
Alesha Thai, MBBS, FRACP, PhD
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
+61 3 8559 5000
Danny Rischin, MD
- Recruiting
Calvary Mater Newcastle
Waratah, New South Wales, 2298
+61 2 40143590
Fiona Day
Canada2 sites, 2 recruiting
- Recruiting
Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec
(514) 890-8000
Antoine Desilets, MD
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
18007110500
Phillippe Bedard, MD
About this study
Official title: 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.
Read the 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.
- 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
- Being tested
- BCA101, Pembrolizumab
- Keywords
- TGFβ, EGFR, pembrolizumab, ficerafusp alfa
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Colorectal Neoplasms, Carcinoma, Ovarian Epithelial, Pancreatic Neoplasms, Head and Neck Neoplasms, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCA101Drug
Also called Ficerafusp alfa
EGFR/TGFβ fusion monoclonal antibody
PembrolizumabDrug
anti-PD-1
| Study group | Role | What they receive |
|---|---|---|
| BCA101 Monotherapy | Experimental | Route: IV Infusion Frequency: QW Current Dose: 1500mg Receives: Drug: BCA101 |
| BCA101 + pembrolizumab | Experimental | Route: IV Infusion Frequency: Q3W Dose: 200mg Receives: Drug: BCA101; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs
Incidence and severity of AEs and SAEs
Measured: 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
Measured: 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.
Measured: 21 days
Secondary outcomes (11)
Objective Response Rate
Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST
Measured: 24 months
Clinical Benefit Rate
Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST
Measured: 24 months
Progression free survival
Determine PFS in each part of the study, per RECIST v1.1 and iRECIST
Measured: 24 months
Duration of Response
Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST
Measured: 24 months
Overall Survival
Determine survival rates in each part of the study.
Measured: 24 months
AUC of BCA101 and pembrolizumab
AUC
Measured: 24 months
Cmax of BCA101 and pembrolizumab
Cmax
Measured: 24 months
Tmax of BCA101 and pembrolizumab
Tmax
Measured: 24 months
Concentration vs time profile of BCA101 and pembrolizumab
Ctrough
Measured: 24 months
Half-life of BCA101 and pembrolizumab
Half-life
Measured: 24 months
Immunogenicity of BCA101 and pembrolizumab
Incidence and titer of anti-drug-antibodies
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2020
- Study start1 Jun 2020
- Primary completion31 Oct 2027 (estimated)
- Study completion30 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 473 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bicara Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04429542
- Sponsor's protocol ID
- BCA101X1101
- Other IDs
- KEYNOTE-E28
- Status last verified
- Oct 2026
- First submitted
- 10 Jun 2020
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hanna GJ, Zandberg DP, Wong DJ, Sherman E, Sacco AG, Yilmaz E, Hernando-Calvo A, Reiners RD, Bohr D, Salazar RL, O'Connell BC, Raben D, Schulten J, Chung CH, Kaczmar J. Ficerafusp Alfa (BCA101) With Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Two-Year Results of an Expansion Cohort of a Phase I/Ib Trial. J Clin Oncol. 2026 Jun 20;44(18):1697-1708. doi: 10.1200/JCO-25-02027. Epub 2026 May 8.
PubMed 42102329