AzTrials
AzTrials

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.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

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
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
Are there results?
Not yet: the study is under way

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:
Show all 20Show fewer
  • 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.
Show all 9Show fewer
  • 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.

David Bohr contact

6178000335

info@bicara.com

21 sites in 3 countries

United States15 sites, 15 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

    Recruiting

Other trials in United States

Australia4 sites, 4 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

    Recruiting

Other trials in Australia

Canada2 sites, 2 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

    Recruiting

Other trials in Canada

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.

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 groups in NCT04429542
Study groupRoleWhat they receive
BCA101 MonotherapyExperimentalRoute: IV Infusion Frequency: QW Current Dose: 1500mg
Receives: Drug: BCA101
BCA101 + pembrolizumabExperimentalRoute: 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.

  1. 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

  2. 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

  3. 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)

  1. Objective Response Rate

    Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST

    Measured: 24 months

  2. Clinical Benefit Rate

    Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST

    Measured: 24 months

  3. Progression free survival

    Determine PFS in each part of the study, per RECIST v1.1 and iRECIST

    Measured: 24 months

  4. Duration of Response

    Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST

    Measured: 24 months

  5. Overall Survival

    Determine survival rates in each part of the study.

    Measured: 24 months

  6. AUC of BCA101 and pembrolizumab

    AUC

    Measured: 24 months

  7. Cmax of BCA101 and pembrolizumab

    Cmax

    Measured: 24 months

  8. Tmax of BCA101 and pembrolizumab

    Tmax

    Measured: 24 months

  9. Concentration vs time profile of BCA101 and pembrolizumab

    Ctrough

    Measured: 24 months

  10. Half-life of BCA101 and pembrolizumab

    Half-life

    Measured: 24 months

  11. 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.

  1. First posted12 Jun 2020
  2. Study start1 Jun 2020
  3. Primary completion31 Oct 2027 (estimated)
  4. Study completion30 Mar 2028 (estimated)

Resources

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)
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

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact David Bohr (6178000335, info@bicara.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs (time frame: 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04429542, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
Clinical Trial NCT04429542 | AzTrials