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

• ClinicalTrials.gov Identifier: NCT04429542
• Recruitment Status: Recruiting
• First Posted: June 12, 2020
• Last Update Posted: January 14, 2021
• Sponsor: Bicara Therapeutics
• Information provided by (Responsible Party): Bicara Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: BCA101; Drug: Pembrolizumab	Phase 1

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. 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.

Study Design

• Study Type: Interventional
• Estimated Enrollment: 292 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 1, 2020
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: June 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: BCA101 Monotherapy; Route: IV Infusion Frequency: QW Dose: 64mg, 240mg, 800mg, 1600mg	Drug: BCA101; EGFR/TGFβ fusion monoclonal antibody
Experimental: BCA101 + pembrolizumab; Route: IV Infusion Frequency: Q3W Dose: 200mg	Drug: BCA101; EGFR/TGFβ fusion monoclonal antibody; Drug: Pembrolizumab; anti-PD-1

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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
3. 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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: David Bohr, MS MPH MBA; 5166037631; david.bohr@bicara.com

Locations

United States, Massachusetts

Dana Farber/Partners Cancer Care Inc; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Karly Griffin 617-632-6287 Karly_Griffin@DFCI.HARVARD.EDU

Principal Investigator: Glen Hanna, MD

United States, New York

Memorial Sloan Kettering; Recruiting

New York, New York, United States, 10017

Contact: Robert C Dyson 646-888-4202 DysonR@mskcc.org

Principal Investigator: Paul Paik, MD

Columbia University Herbert Irving Comprehensive Cancer Center; Recruiting

New York, New York, United States, 10032

Contact: CPDM Nurse Navigator 212-342-5162

Principal Investigator: Richard Carvajal, MD

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Vanda Stepanek, MD PhD CCRP 713-792-4964 vstepane@mdanderson.org

Principal Investigator: Filip Janku, MD

Canada, Ontario

Princess Margaret Cancer Centre; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contact 18007110500

Principal Investigator: Phillippe Bedard, MD

Sponsors and Collaborators

Bicara Therapeutics

More Information

• Responsible Party: Bicara Therapeutics
• ClinicalTrials.gov Identifier: NCT04429542
• Other Study ID Numbers: BCA101X1101
• First Posted: June 12, 2020
• Last Update Posted: January 14, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Bicara Therapeutics:

TGFβ; EGFR

Additional relevant MeSH terms:

Glioblastoma; Carcinoma; Carcinoma, Squamous Cell; Triple Negative Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Ovarian Epithelial; Pancreatic Neoplasms; Chordoma; Thyroid Carcinoma, Anaplastic; Lung Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Neoplasms, Squamous Cell; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Astrocytoma; Glioma