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

Trial Status: Active

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.

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 Lung Cancer (SqCLC) 2) Squamous Cell Carcinoma of the Head and Neck (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:
  • HNSCC
  • 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:
  • PD-L1 negative, EGFR-amplified SqCLC
  • RAS WT MSS CRC
  • EGFR-amplified TNBC
  • Any solid tumor with a KRAS G12D or G13D mutation ii. Combination BCA101 and pembrolizumab - patients with the following tumor types will be eligible:

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.

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Paul K. Paik
Phone: 646-888-4202
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE
Contact: Vanda Stepanek
Phone: 713-792-4964

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.

Planned expansion cohorts for single agent BCA101 include 1) PD-L1 negative, EGFR-amplified

Squamous Cell Lung Cancer (SqCLC); 2) RAS wild-type, microsatellite stable Colorectal

Carcinoma (RAS wt, MSS CRC); 3) EGFR-amplified Triple Negative Breast Cancer; and 4) any

solid tumor with either a KRAS G12D or G13D mutation. Planned expansion cohorts for the

combination of BCA101 and pembrolizumab include: 1) HNSCC and 2) SCCAC.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Bicara Therapeutics

  • Primary ID BCA101X1101
  • Secondary IDs NCI-2020-04796
  • Clinicaltrials.gov ID NCT04429542