Clinical Trials /

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

NCT04429542

Description:

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.

Related Conditions:
  • Anal Canal Squamous Cell Carcinoma
  • Breast Carcinoma
  • Chordoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Glioblastoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Squamous Cell Lung Carcinoma
  • Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Safety and Tolerability of BCA101 Alone and in Combination With Pembrolizumab 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 Alone and in Combination With Pembrolizumab in Patients With EGFR-Driven Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BCA101X1101
  • NCT ID: NCT04429542

Conditions

  • TNBC - Triple-Negative Breast Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Squamous Cell Carcinoma of Anal Canal
  • Uveal Melanoma
  • Glioblastoma
  • Colorectal Cancer
  • Chordoma
  • Squamous Cell Carcinoma of the Lung
  • KRAS G12D
  • KRAS G13D
  • EGFR Amplification
  • Epithelial Ovarian Cancer
  • Hepatocellular Carcinoma
  • Anaplastic Thyroid Cancer
  • Pancreas Cancer

Interventions

DrugSynonymsArms
BCA101BCA101 + pembrolizumab
PembrolizumabBCA101 + pembrolizumab

Purpose

The investigational drug to be studied in this protocol, BCA101, is a first-in-class compound that combines EGFR with TGFβ. Based on preclinical data, this dual targeted, 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 first dose escalation part will be conducted with single agent BCA101
      in subjects with advanced EGFR-driven advanced solid tumors.

      The study population in Part A consists of subjects with EGFR-driven advanced solid tumors
      who are refractory to standard of care or for whom standard of care is not available.
      Targeting both the EGFR and TGFβ pathways may provide synergistic activity in these patients.
      This dose-finding part of the study will lead to selected subject population in Part B of the
      study.

      Once the maximum tolerated dose (MTD) / recommended dose (RD) of single agent BCA101 is
      determined, the study will continue with expansion cohorts with select tumor types. Part A
      consists of another dose escalation part of BCA101 and pembrolizumab in head and neck
      squamous cell carcinoma and squamous cell carcinoma of the anal canal, followed by an
      expansion part.

      Part B (cohort expansion) will begin enrolling subjects once the corresponding arm has
      established an RD. Planned expansion cohorts for single agent BCA101 include 1) PD-L1
      negative, EGFR-amplified squamous cell cancer of the lung; 2) RAS wild-type, microsatellite
      stable colorectal carcinoma; 3) EGFR-amplified triple negative breast cancer; and 4) any
      solid tumor with a KRAS G12D or G13D mutation. Planned expansion cohorts for the combination
      of BCA101 and pembrolizumab include: 1) head and neck squamous cell carcinoma and 2) squamous
      cell carcinoma of the anal canal.
    

Trial Arms

NameTypeDescriptionInterventions
BCA101 MonotherapyExperimentalRoute: IV Infusion Frequency: QW Dose: 64mg, 240mg, 800mg, 1600mg
  • BCA101
BCA101 + pembrolizumabExperimentalRoute: IV Infusion Frequency: Q3W Dose: 200mg
  • BCA101
  • Pembrolizumab

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 A (Dose Escalation): Patient must have histologically or cytologically confirmed,
        EGFR-driven, advanced solid tumor refractory to current standard of care therapy.

        i Single agent BCA101 - patients with the following tumor types will be eligible: 1)
        Squamous cell carcinoma of the lung (SQCLC) 2) Head and neck squamous cell carcinoma
        (HNSCC) 3) RAS wild type microsatellite stable colorectal carcinoma (RAS WT MSS CRC) 4)
        Triple negative breast cancer (TNBC) 5) Chordoma 6) Squamous cell carcinoma of the anal
        canal (SCCAC) 7) Uveal melanoma 8) Glioblastoma (GBM) 9) Gastric cancer 10) Any solid tumor
        with a KRAS G12D or G13D mutation 11) Any solid tumor with EGFR amplification 12)
        Epithelial ovarian cancer 13) Hepatocellular carcinoma (HCC) 14) Anaplastic thyroid cancer
        (ATC) 15) Pancreatic cancer 16) Other EGFR-driven advanced solid tumors (if there is
        compelling data or evidence to enroll a patient with a tumor type other than those listed
        in 1 - 15, the treating physician may discuss the patient with the Sponsor to determine
        eligibility). ii. Combination BCA101 and pembrolizumab - patients with the following tumor
        types will be eligible:

          1. HNSCC

          2. SCCAC

        PART B (Cohort expansion): Patients must have histologically or cytologically confirmed
        EGFR-driven, advanced solid tumor refractory to current standard of care therapy.

        i Single agent BCA101 - patients with the following tumor types will be eligible:

          1. PD-L1 negative, EGFR-amplified SQCLC

          2. CRC RAS, WT MSS

          3. EGFR-amplified TNBC

          4. Any solid tumor with a KRAS G12D or G13D mutation ii. Combination BCA101 and
             pembrolizumab - patients with the following tumor types will be eligible:

        1) HNSCC 2) SCCAC

        Exclusion Criteria:

          -  Exposure to anti-EGFR antibodies within 4 weeks of the first dose of study drug or any
             history of treatment with anti-TGFβ therapies.

          -  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.

          -  For Part B only: Prior history of Grade ≥ 2 intolerance or hypersensitivity reaction
             to immune checkpoint inhibitors or any history of treatment discontinuation in the
             setting of toxicity to an immune checkpoint inhibitor.

          -  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 case of human immunodeficiency virus (HIV), or active hepatitis B (hepatitis B
             surface antigen; HBsAg) or hepatitis C.

        Note: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
        (defined as having a negative HBsAg test and a positive antibody to hepatitis B core
        antigen [anti HBc] antibody test) are eligible. Patients positive for hepatitis C virus
        (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs
Time Frame:24 months
Safety Issue:
Description:Incidence and severity of AEs and SAEs

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bicara Therapeutics

Trial Keywords

  • TGFβ
  • EGFR

Last Updated

June 11, 2020