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

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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 Phase

Phase 1

Study Type

Interventional


Primary Outcome

Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs

Secondary Outcome

 Objective Response Rate

Condition

Head and Neck Squamous Cell Carcinoma

Intervention

BCA101

Study Arms / Comparison Groups

 BCA101 Monotherapy
Description:  Route: IV Infusion Frequency: QW Current Dose: 1500mg

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

292

Start Date

June 1, 2020

Completion Date

June 1, 2024

Primary Completion Date

December 31, 2023

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.

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, 6178000335, [email protected]

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT04429542

Organization ID

BCA101X1101

Secondary IDs

KEYNOTE-E28

Responsible Party

Sponsor

Study Sponsor

Bicara Therapeutics

Collaborators

 Merck Sharp & Dohme LLC

Study Sponsor

, , 


Verification Date

September 2022