- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04429542
Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors
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
Study Overview
Status
Conditions
- Head and Neck Neoplasms
- Carcinoma, Squamous Cell
- Colorectal Cancer
- Squamous Cell Carcinoma of Head and Neck
- Epithelial Ovarian Cancer
- Head and Neck Squamous Cell Carcinoma
- Pancreas Cancer
- Squamous Cell Carcinoma of the Lung
- Cutaneous Squamous Cell Carcinoma
- Squamous Cell Carcinoma of Anal Canal
- EGFR Amplification
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: David Bohr
- Phone Number: 6178000335
- Email: info@bicara.com
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5G 2M9
- Recruiting
- Princess Margaret Cancer Centre
-
Contact:
- Phone Number: 18007110500
-
Principal Investigator:
- Phillippe Bedard, MD
-
-
-
-
California
-
La Jolla, California, United States, 92093
- Recruiting
- Moores Cancer Center UC San Diego Health
-
Contact:
- Debanjali Ghosh
- Phone Number: 858-246-0357
- Email: d1ghosh@health.ucsd.edu
-
Principal Investigator:
- Assuntina Sacco, MD
-
Los Angeles, California, United States, 90095
- Recruiting
- UCLA
-
Principal Investigator:
- Deborah Wong, MD
-
Los Angeles, California, United States, 90033
- Recruiting
- Keck School of Medicine of USC
-
Principal Investigator:
- Gino In, MD
-
-
Florida
-
Tampa, Florida, United States, 33612
- Recruiting
- H. Lee Moffitt Cancer Center and Research Institute, Inc
-
Contact:
- Hamza Elmohd
- Phone Number: 813-745-5554
- Email: Hamza.elmohd@moffitt.org
-
Principal Investigator:
- Jameel Muzaffar, MD
-
-
Kentucky
-
Lexington, Kentucky, United States, 40536
- Recruiting
- Markey Cancer Center
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Recruiting
- Dana Farber/Partners Cancer Care Inc
-
Principal Investigator:
- Glen Hanna, MD
-
Contact:
- DFCI Clinical Trials Hotline
- Phone Number: 877-338-7425
-
-
New York
-
New York, New York, United States, 10032
- Recruiting
- Columbia University Herbert Irving Comprehensive Cancer Center
-
Contact:
- CPDM Nurse Navigator
- Phone Number: 212-342-5162
- Email: cancerclinicaltrials@cumc.columbia.edu
-
New York, New York, United States, 10017
- Recruiting
- Memorial Sloan Kettering
-
Contact:
- Phone Number: 646-608-3759
-
Principal Investigator:
- Paul Paik, MD
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- Recruiting
- Cleveland Clinic
-
Contact:
- Phone Number: 866-223-8100
- Email: TaussigResearch@ccf.org
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15232
- Recruiting
- UPMC Hillman Cancer Center
-
Contact:
- Sarah Brodeur
- Email: brodeurs@upmc.edu
-
Principal Investigator:
- Dan Zanberg, MD
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02903
- Recruiting
- Rhode Island Hospital
-
-
South Carolina
-
Charleston, South Carolina, United States, 29425
- Recruiting
- Medical University of South Carolina, Hollings Cancer Center
-
Contact:
- Lilli Neal
- Phone Number: 843-792-8113
- Email: nealli@musc.edu
-
Contact:
- Carly Fecio
- Phone Number: 8437923479
- Email: fecio@musc.edu
-
Principal Investigator:
- John Kaczmar, MD
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Recruiting
- Vanderbilt University Medical Center
-
Principal Investigator:
- Mike Gibson, MD
-
Contact:
- MD
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- MD Anderson Cancer Center
-
Contact:
- Beryl Tross
- Phone Number: 713-745-0774
- Email: bmtross@mdanderson.org
-
Principal Investigator:
- Van Morris, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
- Expansion Cohort 5: Squamous Non-Small Cell Lung Cancer (SqNSCLC) i. Patients must have a histologically or cytologically confirmed diagnosis of stage IV (AJCC 8th edition) squamous NSCLC. Patients with mixed histology (e.g., adenosquamous) are not allowed.
ii. Patients must have progressed on one prior systemic therapy in the metastatic setting.
iii. No prior history of treatment with anti-EGFR antibodies in the metastatic setting.
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BCA101 Monotherapy
Route: IV Infusion Frequency: QW Current Dose: 1500mg
|
EGFR/TGFβ fusion monoclonal antibody
|
Experimental: BCA101 + pembrolizumab
Route: IV Infusion Frequency: Q3W Dose: 200mg
|
EGFR/TGFβ fusion monoclonal antibody
anti-PD-1
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
24 months
|
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
|
24 months
|
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.
|
21 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate
Time Frame: 24 months
|
Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST
|
24 months
|
Clinical Benefit Rate
Time Frame: 24 months
|
Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST
|
24 months
|
Progression free survival
Time Frame: 24 months
|
Determine PFS in each part of the study, per RECIST v1.1 and iRECIST
|
24 months
|
Duration of Response
Time Frame: 24 months
|
Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST
|
24 months
|
Overall Survival
Time Frame: 24 months
|
Determine survival rates in each part of the study.
|
24 months
|
AUC of BCA101 and pembrolizumab
Time Frame: 24 months
|
AUC
|
24 months
|
Cmax of BCA101 and pembrolizumab
Time Frame: 24 months
|
Cmax
|
24 months
|
Tmax of BCA101 and pembrolizumab
Time Frame: 24 months
|
Tmax
|
24 months
|
Concentration vs time profile of BCA101 and pembrolizumab
Time Frame: 24 months
|
Ctrough
|
24 months
|
Half-life of BCA101 and pembrolizumab
Time Frame: 24 months
|
Half-life
|
24 months
|
Immunogenicity of BCA101 and pembrolizumab
Time Frame: 24 months
|
Incidence and titer of anti-drug-antibodies
|
24 months
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Pancreatic Diseases
- Neoplasms, Squamous Cell
- Ovarian Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Head and Neck Neoplasms
- Lung Neoplasms
- Carcinoma
- Pancreatic Neoplasms
- Carcinoma, Ovarian Epithelial
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- BCA101X1101
- KEYNOTE-E28 (Other Identifier: Merck Sharp & Dohme LLC)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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