Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors

NCT ID: NCT04429542

Last Updated: 2025-08-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

292 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-01

Study Completion Date

2027-06-01

Brief Summary

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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.

Detailed Description

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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

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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BCA101 Monotherapy

Route: IV Infusion Frequency: QW Current Dose: 1500mg

Group Type EXPERIMENTAL

BCA101

Intervention Type DRUG

EGFR/TGFβ fusion monoclonal antibody

BCA101 + pembrolizumab

Route: IV Infusion Frequency: Q3W Dose: 200mg

Group Type EXPERIMENTAL

BCA101

Intervention Type DRUG

EGFR/TGFβ fusion monoclonal antibody

Pembrolizumab

Intervention Type DRUG

anti-PD-1

Interventions

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BCA101

EGFR/TGFβ fusion monoclonal antibody

Intervention Type DRUG

Pembrolizumab

anti-PD-1

Intervention Type DRUG

Other Intervention Names

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Ficerafusp alfa

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Bicara Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Moores Cancer Center UC San Diego Health

La Jolla, California, United States

Site Status RECRUITING

Keck School of Medicine of USC

Los Angeles, California, United States

Site Status RECRUITING

UCLA

Los Angeles, California, United States

Site Status RECRUITING

University of California, Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status RECRUITING

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, United States

Site Status RECRUITING

Dana Farber/Partners Cancer Care Inc

Boston, Massachusetts, United States

Site Status RECRUITING

Memorial Sloan Kettering

New York, New York, United States

Site Status RECRUITING

Columbia University Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status RECRUITING

Medical University of South Carolina, Hollings Cancer Center

Charleston, South Carolina, United States

Site Status RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Site Status RECRUITING

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Site Status RECRUITING

Austin Hospital

Heidelberg, Victoria, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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United States Australia Canada

Central Contacts

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David Bohr

Role: CONTACT

6178000335

Facility Contacts

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Debanjali Ghosh

Role: primary

858.246.0357

Andrew Birkeland, MD

Role: primary

Hamza Elmohd

Role: primary

(813)-745-5554

DFCI Clinical Trials Hotline

Role: primary

8773387425

Role: primary

646-608-3759

CPDM Nurse Navigator

Role: primary

2123425162

Daniel R Carrizosa, MD, MS, FACP

Role: primary

980-442-3213

Role: primary

(866) 223-8100

Sarah Brodeur

Role: primary

Lilli Neal

Role: primary

8437928113

Carly Fecio

Role: backup

8437923479

Beryl Tross

Role: primary

7137450774

Jenny Lee, MBBS, FRACP

Role: primary

Role: primary

+61 2 40143590

Alesha Thai, MBBS, FRACP, PhD

Role: primary

+61394965000

Role: primary

+61 3 8559 5000

Role: primary

18007110500

Other Identifiers

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KEYNOTE-E28

Identifier Type: OTHER

Identifier Source: secondary_id

BCA101X1101

Identifier Type: -

Identifier Source: org_study_id

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