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

Tracking Information

• First Submitted Date: June 10, 2020
• First Posted Date: June 12, 2020
• Last Update Posted Date: January 3, 2024
• Actual Study Start Date: June 1, 2020
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 11, 2020)

• 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
• 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
• 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 11, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors
• 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
• 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.

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
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

• Drug: BCA101
  EGFR/TGFβ fusion monoclonal antibody
• Drug: Pembrolizumab
  anti-PD-1

Study Arms

• Experimental: BCA101 Monotherapy
  Route: IV Infusion Frequency: QW Current Dose: 1500mg
  Intervention: Drug: BCA101
• Experimental: BCA101 + pembrolizumab
  Route: IV Infusion Frequency: Q3W Dose: 200mg
  Interventions:

  • Drug: BCA101
  • Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 11, 2020): 292
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 1, 2025
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT04429542
• Other Study ID Numbers: BCA101X1101; KEYNOTE-E28 ( Other Identifier: Merck Sharp & Dohme LLC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bicara Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Bicara Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Not Provided
• PRS Account: Bicara Therapeutics
• Verification Date: January 2024