Overview

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

Status:
Recruiting
Trial end date:
2023-06-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Bicara Therapeutics
Treatments:
Pembrolizumab
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 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:

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. RAS WT MSS CRC

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.