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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04429542
Recruitment Status : Recruiting
First Posted : June 12, 2020
Last Update Posted : January 14, 2021
Sponsor:
Information provided by (Responsible Party):
Bicara Therapeutics

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.

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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


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




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04429542


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

Locations
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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
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Responsible Party: Bicara Therapeutics
ClinicalTrials.gov Identifier: NCT04429542    
Other Study ID Numbers: BCA101X1101
First Posted: June 12, 2020    Key Record Dates
Last Update Posted: January 14, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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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