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Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy 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 : July 20, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
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
Head and Neck Squamous Cell Carcinoma Squamous Cell Carcinoma of Anal Canal Colorectal Cancer Squamous Cell Carcinoma of the Lung EGFR Amplification Epithelial Ovarian Cancer Pancreas Cancer Cutaneous Squamous Cell Carcinoma Head and Neck Neoplasms Carcinoma, Squamous Cell Squamous Cell Carcinoma of Head and Neck 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. Expansion cohorts for single agent BCA101 will include cutaneous squamous cell carcinoma. Planned expansion cohorts for the combination of BCA101 and pembrolizumab include: 1) HNSCC and 2) SCCAC.

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Study Type : Interventional  (Clinical Trial)
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 Monotherapy and in Combination Therapy 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 Current Dose: 1500mg
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 B (Cohort expansion):

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

• Expansion Cohort 1: Cutaneous Squamous Cell Carcinoma (CSCC) - i. patients must have received (or been intolerant to or ineligible for) prior anti-PD-1 therapy in the metastatic or locally advanced setting.

ii. No prior history of treatment with anti-EGFR antibodies in the unresectable/metastatic setting (prior treatment with radiotherapy in the adjuvant setting is allowed).

ii. Combination BCA101 and pembrolizumab - patients with the following tumor types will be eligible: • Expansion Cohort 2: Head and Neck Squamous Cell Carcinoma (HNSCC), metastatic or unresectable, recurrent with a Combined Positive Score (CPS) equal to or greater than 1, as determined by an CLIA-approved laboratory test. Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology).

i. Patients must have no prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally advanced disease) or prior history of immune checkpoint inhibitors with the exception of neoadjuvant therapy (>6 months prior to study drug initiation). No prior history of anti-EGFR antibodies (with the exception of radiosensitizing agents and multimodal treatment for locally advanced disease).

ii. Patients must provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate is not sufficient): A newly obtained biopsy (within 90 days prior to start of study treatment) is preferred but an archival sample is acceptable.

iii. Patients must have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer

• Expansion Cohort 3: Squamous Carcinoma of the Anal Canal (SCAC), locally advanced/unresectable or metastatic.

i. Patients must have received (or been intolerant to or ineligible for) at least 1 prior line of chemotherapy and received no more than 2 prior lines of systemic treatments for treatment of unresectable and/or metastatic disease. No prior history of immune checkpoint inhibitors.

Exclusion Criteria:

  • For Part A: Exposure to anti-EGFR antibodies within 4 weeks of the first dose of study drug.
  • Prior treatment with any anti-TGFβ therapy.
  • 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.
  • 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 history of a hematologic malignancy (or solid tumor other than the ones indicated for this study), unless the patient has undergone potentially curative therapy with no evidence of that disease for 2 years. Does not include tumors with a negligible risk of metastasis or death (e.g. adequately treated basal or squamous cell carcinoma, stage 1 prostate cancer, or carcinoma in situ of the cervix or carcinoma in situ of the breast). Subjects enrolling in the CSCC cohort may have chronic lymphocytic leukemia as long as the patient is not on active treatment.
  • Known cases of human immunodeficiency virus (HIV) are excluded if patients have a CD4+ T-cell (CD4+) count <250 cells/uL. To ensure that effective antiretroviral therapy (ART) is tolerated and that toxicities are not confused with investigational drug toxicities, trial participants should be on established ART for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
  • Patients with chronic HBV infection with active disease who meet the criteria for anti-HBV therapy and are not on a suppressive antiviral therapy prior to initiation of study treatment
  • Patients with a known history of hepatitis C who have not completed curative antiviral treatment or have a HCV viral load above the limit of quantification

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 6178000335 info@bicara.com

Locations
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United States, California
Moores Cancer Center UC San Diego Health Not yet recruiting
La Jolla, California, United States, 92093
Contact: Debanjali Ghosh    858-246-0357    d1ghosh@health.ucsd.edu   
Principal Investigator: Assuntina Sacco, MD         
UCLA Recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Deborah Wong, MD         
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute, Inc Recruiting
Tampa, Florida, United States, 33612
Contact: Hamza Elmohd    813-745-5554    Hamza.elmohd@moffitt.org   
Principal Investigator: Jameel Muzaffar, MD         
United States, Massachusetts
Dana Farber/Partners Cancer Care Inc Recruiting
Boston, Massachusetts, United States, 02115
Contact: DFCI Clinical Trials Hotline    877-338-7425      
Principal Investigator: Glen Hanna, MD         
United States, New York
Memorial Sloan Kettering Recruiting
New York, New York, United States, 10017
Contact    646-608-3759      
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    cancerclinicaltrials@cumc.columbia.edu   
Principal Investigator: Richard Carvajal, MD         
United States, Pennsylvania
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Sarah Brodeur       brodeurs@upmc.edu   
Principal Investigator: Dan Zanberg, MD         
United States, South Carolina
Medical University of South Carolina, Hollings Cancer Center Recruiting
Charleston, South Carolina, United States, 29425
Contact: Lilli Neal    843-792-8113    nealli@musc.edu   
Contact: Carly Fecio    8437923479    fecio@musc.edu   
Principal Investigator: John Kaczmar, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Beryl Tross    713-745-0774    bmtross@mdanderson.org   
Principal Investigator: Van Morris, 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
Merck Sharp & Dohme LLC
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Responsible Party: Bicara Therapeutics
ClinicalTrials.gov Identifier: NCT04429542    
Other Study ID Numbers: BCA101X1101
KEYNOTE-E28 ( Other Identifier: Merck Sharp & Dohme LLC )
First Posted: June 12, 2020    Key Record Dates
Last Update Posted: July 20, 2022
Last Verified: July 2022
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
pembrolizumab
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Carcinoma, Ovarian Epithelial
Pancreatic Neoplasms
Head and Neck Neoplasms
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
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
Pancreatic Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents