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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04429542




Registration number
NCT04429542
Ethics application status
Date submitted
10/06/2020
Date registered
12/06/2020

Titles & IDs
Public title
Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients with EGFR-driven Advanced Solid Tumors
Scientific title
First-in-Human, Phase 1/1b, Open-label, Multicenter Study of Bifunctional EGFR/TGFß Fusion Protein BCA101 Monotherapy and in Combination Therapy in Patients with EGFR-Driven Advanced Solid Tumors
Secondary ID [1] 0 0
KEYNOTE-E28
Secondary ID [2] 0 0
BCA101X1101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Squamous Cell Carcinoma 0 0
Squamous Cell Carcinoma of Anal Canal 0 0
Colorectal Cancer 0 0
Squamous Cell Carcinoma of the Lung 0 0
EGFR Amplification 0 0
Epithelial Ovarian Cancer 0 0
Pancreas Cancer 0 0
Cutaneous Squamous Cell Carcinoma 0 0
Head and Neck Neoplasms 0 0
Carcinoma, Squamous Cell 0 0
Squamous Cell Carcinoma of Head and Neck 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Pancreatic
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BCA101
Treatment: Drugs - Pembrolizumab

Experimental: BCA101 Monotherapy - Route: IV Infusion Frequency: QW Current Dose: 1500mg

Experimental: BCA101 + pembrolizumab - Route: IV Infusion Frequency: Q3W Dose: 200mg


Treatment: Drugs: BCA101
EGFR/TGFß fusion monoclonal antibody

Treatment: Drugs: Pembrolizumab
anti-PD-1
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs
Timepoint [1] 0 0
24 months
Primary outcome [2] 0 0
Tolerability of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs
Timepoint [2] 0 0
24 months
Primary outcome [3] 0 0
Incidence of Dose Limiting Toxicities (DLTs)
Timepoint [3] 0 0
21 days
Secondary outcome [1] 0 0
Objective Response Rate
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Clinical Benefit Rate
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Progression free survival
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Duration of Response
Timepoint [4] 0 0
24 months
Secondary outcome [5] 0 0
Overall Survival
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
AUC of BCA101 and pembrolizumab
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
Cmax of BCA101 and pembrolizumab
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Tmax of BCA101 and pembrolizumab
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Concentration vs time profile of BCA101 and pembrolizumab
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
Half-life of BCA101 and pembrolizumab
Timepoint [10] 0 0
24 months
Secondary outcome [11] 0 0
Immunogenicity of BCA101 and pembrolizumab
Timepoint [11] 0 0
24 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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-TGFß 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2027
Actual
Sample size
Target
292
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Rhode Island
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bicara Therapeutics
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
David Bohr
Address 0 0
Country 0 0
Phone 0 0
6178000335
Fax 0 0
Email 0 0
info@bicara.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04429542