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

• ClinicalTrials.gov Identifier: NCT04429542
• Recruitment Status: Recruiting
• First Posted: June 12, 2020
• Last Update Posted: January 3, 2024
• Sponsor: Bicara Therapeutics
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Bicara Therapeutics

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
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	Drug: BCA101; Drug: Pembrolizumab	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 292 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 1, 2020
• Estimated Primary Completion Date: December 31, 2024
• Estimated Study Completion Date: June 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: BCA101 Monotherapy; Route: IV Infusion Frequency: QW Current Dose: 1500mg	Drug: BCA101; EGFR/TGFβ fusion monoclonal antibody
Experimental: BCA101 + pembrolizumab; Route: IV Infusion Frequency: Q3W Dose: 200mg	Drug: BCA101; EGFR/TGFβ fusion monoclonal antibody; Drug: Pembrolizumab; anti-PD-1

Outcome Measures

Primary Outcome Measures :

1. Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs [ Time Frame: 24 months ]
   Incidence and severity of AEs and SAEs
2. Tolerability of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs [ Time Frame: 24 months ]
   Incidence and severity of AEs and SAEs
3. Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 21 days ]
   Incidence of DLTs during the first cycle of treatment with BCA101 monotherapy or the combination of BCA101 and pembrolizumab.

Secondary Outcome Measures :

1. Objective Response Rate [ Time Frame: 24 months ]
   Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST
2. Clinical Benefit Rate [ Time Frame: 24 months ]
   Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST
3. Progression free survival [ Time Frame: 24 months ]
   Determine PFS in each part of the study, per RECIST v1.1 and iRECIST
4. Duration of Response [ Time Frame: 24 months ]
   Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST
5. Overall Survival [ Time Frame: 24 months ]
   Determine survival rates in each part of the study.
6. AUC of BCA101 and pembrolizumab [ Time Frame: 24 months ]
   AUC
7. Cmax of BCA101 and pembrolizumab [ Time Frame: 24 months ]
   Cmax
8. Tmax of BCA101 and pembrolizumab [ Time Frame: 24 months ]
   Tmax
9. Concentration vs time profile of BCA101 and pembrolizumab [ Time Frame: 24 months ]
   Ctrough
10. Half-life of BCA101 and pembrolizumab [ Time Frame: 24 months ]
    Half-life
11. Immunogenicity of BCA101 and pembrolizumab [ Time Frame: 24 months ]
    Incidence and titer of anti-drug-antibodies

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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):

i. 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).

ii. 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.

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

Contacts and Locations

Contacts

Contact: David Bohr; 6178000335; info@bicara.com

Locations

United States, California

Moores Cancer Center UC San Diego Health; Recruiting

La Jolla, California, United States, 92093

Contact: Debanjali Ghosh 858-246-0357 d1ghosh@health.ucsd.edu

Principal Investigator: Assuntina Sacco, MD

Keck School of Medicine of USC; Recruiting

Los Angeles, California, United States, 90033

Principal Investigator: Gino In, MD

UCLA; Recruiting

Los Angeles, California, United States, 90095

Principal Investigator: Deborah Wong, MD

United States, Florida

H. Lee Moffitt Cancer Center and Research Institute, Inc; Recruiting

Tampa, Florida, United States, 33612

Contact: Hamza Elmohd 813-745-5554 Hamza.elmohd@moffitt.org

Principal Investigator: Jameel Muzaffar, MD

United States, Kentucky

Markey Cancer Center; Recruiting

Lexington, Kentucky, United States, 40536

United States, Massachusetts

Dana Farber/Partners Cancer Care Inc; Recruiting

Boston, Massachusetts, United States, 02115

Contact: DFCI Clinical Trials Hotline 877-338-7425

Principal Investigator: Glen Hanna, MD

United States, New York

Memorial Sloan Kettering; Recruiting

New York, New York, United States, 10017

Contact 646-608-3759

Principal Investigator: Paul Paik, MD

Columbia University Herbert Irving Comprehensive Cancer Center; Recruiting

New York, New York, United States, 10032

Contact: CPDM Nurse Navigator 212-342-5162 cancerclinicaltrials@cumc.columbia.edu

United States, Ohio

Cleveland Clinic; Recruiting

Cleveland, Ohio, United States, 44195

Contact 866-223-8100 TaussigResearch@ccf.org

United States, Pennsylvania

UPMC Hillman Cancer Center; Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contact: Sarah Brodeur brodeurs@upmc.edu

Principal Investigator: Dan Zanberg, MD

United States, Rhode Island

Rhode Island Hospital; Recruiting

Providence, Rhode Island, United States, 02903

United States, South Carolina

Medical University of South Carolina, Hollings Cancer Center; Recruiting

Charleston, South Carolina, United States, 29425

Contact: Lilli Neal 843-792-8113 nealli@musc.edu

Contact: Carly Fecio 8437923479 fecio@musc.edu

Principal Investigator: John Kaczmar, MD

United States, Tennessee

Vanderbilt University Medical Center; Recruiting

Nashville, Tennessee, United States, 37232

Contact: MD

Principal Investigator: Mike Gibson, MD

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Beryl Tross 713-745-0774 bmtross@mdanderson.org

Principal Investigator: Van Morris, MD

Canada, Ontario

Princess Margaret Cancer Centre; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contact 18007110500

Principal Investigator: Phillippe Bedard, MD

Sponsors and Collaborators

Bicara Therapeutics

Merck Sharp & Dohme LLC

More Information

• Responsible Party: Bicara Therapeutics
• ClinicalTrials.gov Identifier: NCT04429542
• Other Study ID Numbers: BCA101X1101; KEYNOTE-E28 ( Other Identifier: Merck Sharp & Dohme LLC )
• First Posted: June 12, 2020
• Last Update Posted: January 3, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bicara Therapeutics:

TGFβ; EGFR; pembrolizumab

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Ovarian Epithelial; Pancreatic Neoplasms; Head and Neck Neoplasms; Lung Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Neoplasms, Squamous Cell; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Pancreatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms