Estudio de seguridad y tolerabilidad de BCA101 en monoterapia y en terapia combinada en pacientes con tumores sólidos avanzados impulsados por EGFR
Primer estudio en humanos, de fase 1/1b, abierto, multicéntrico de la proteína de fusión bifuncional EGFR/TGFβ BCA101 en monoterapia y en terapia combinada en pacientes con tumores sólidos avanzados impulsados por EGFR
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.
Descripción general del estudio
Estado
Condiciones
- Neoplasias de Cabeza y Cuello
- Carcinoma De Células Escamosas
- Cáncer colonrectal
- Carcinoma de células escamosas de cabeza y cuello
- Cáncer epitelial de ovario
- Carcinoma de células escamosas de cabeza y cuello
- Cáncer de páncreas
- Carcinoma de células escamosas de pulmón
- Carcinoma cutáneo de células escamosas
- Carcinoma de células escamosas del canal anal
- Amplificación de EGFR
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: David Bohr
- Número de teléfono: 6178000335
- Correo electrónico: info@bicara.com
Ubicaciones de estudio
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New South Wales
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Camperdown, New South Wales, Australia, 2050
- Reclutamiento
- Chris O'Brien Lifehouse
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Investigador principal:
- Jenny Lee, MBBS, FRACP
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Contacto:
- Número de teléfono: (02) 8514 0000
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Waratah, New South Wales, Australia, 2298
- Reclutamiento
- Calvary Mater Newcastle
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Contacto:
- Número de teléfono: +61 2 40143590
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Investigador principal:
- Fiona Day
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Victoria
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Heidelberg, Victoria, Australia, 3084
- Reclutamiento
- Austin Hospital
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Contacto:
- Número de teléfono: +61394965000
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Investigador principal:
- Alesha Thai, MBBS, FRACP, PhD
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Melbourne, Victoria, Australia, 3000
- Reclutamiento
- Peter MacCallum Cancer Centre
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Contacto:
- Número de teléfono: +61 3 8559 5000
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Investigador principal:
- Danny Rischin, MD
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Ontario
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Toronto, Ontario, Canadá, M5G 2M9
- Reclutamiento
- Princess Margaret Cancer Centre
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Contacto:
- Número de teléfono: 18007110500
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Investigador principal:
- Phillippe Bedard, MD
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Quebec
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Montreal, Quebec, Canadá
- Reclutamiento
- Centre hospitalier de l'Université de Montréal (CHUM)
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Contacto:
- Número de teléfono: (514) 890-8000
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Investigador principal:
- Antoine Desilets, MD
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California
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La Jolla, California, Estados Unidos, 92093
- Reclutamiento
- Moores Cancer Center UC San Diego Health
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Investigador principal:
- Assuntina Sacco, MD
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Contacto:
- Moores UCSD Cancer Center Clinical Trials Office
- Número de teléfono: 858-822-5354
- Correo electrónico: d1ghosh@health.ucsd.edu
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Los Angeles, California, Estados Unidos, 90095
- Reclutamiento
- UCLA
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Investigador principal:
- Deborah Wong, MD
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Contacto:
- UCLA Clinical Trials Office
- Número de teléfono: 310-794-8783
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Los Angeles, California, Estados Unidos, 90033
- Reclutamiento
- Keck School of Medicine of USC
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Investigador principal:
- Gino In, MD
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Contacto:
- Clinical Trials Office
- Número de teléfono: 323-442-1900
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Sacramento, California, Estados Unidos, 95817
- Reclutamiento
- University of California, Davis Comprehensive Cancer Center
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Investigador principal:
- Andrew Birkeland, MD
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Contacto:
- Clinical Trials Office
- Número de teléfono: 916-703-9184
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Florida
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Tampa, Florida, Estados Unidos, 33612
- Reclutamiento
- H. Lee Moffitt Cancer Center and Research Institute, Inc
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Investigador principal:
- Christine Chung, MD
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Contacto:
- Clinical Trials Office
- Número de teléfono: 813-945-3563
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Reclutamiento
- Dana Farber/Partners Cancer Care Inc
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Contacto:
- DFCI Clinical Trials Hotline
- Número de teléfono: 877-338-7425
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Investigador principal:
- Michael Dennis, MD
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New York
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New York, New York, Estados Unidos, 10032
- Reclutamiento
- Columbia University Herbert Irving Comprehensive Cancer Center
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Contacto:
- CPDM Nurse Navigator
- Número de teléfono: 212-342-5162
- Correo electrónico: cancerclinicaltrials@cumc.columbia.edu
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Investigador principal:
- Catherine Shu, MD
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New York, New York, Estados Unidos, 10017
- Reclutamiento
- Memorial Sloan Kettering
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Contacto:
- Número de teléfono: 646-608-3759
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Investigador principal:
- Eric Sherman, MD
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North Carolina
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Charlotte, North Carolina, Estados Unidos, 28204
- Reclutamiento
- Levine Cancer Institute
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Investigador principal:
- Daniel Carrizosa, MD
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Contacto:
- Número de teléfono: 980-442-3213
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Ohio
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Cleveland, Ohio, Estados Unidos, 44195
- Reclutamiento
- Cleveland Clinic
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Contacto:
- Número de teléfono: 866-223-8100
- Correo electrónico: TaussigResearch@ccf.org
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Investigador principal:
- Tamara Sussman, MD
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15232
- Reclutamiento
- UPMC Hillman Cancer Center
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Investigador principal:
- Dan Zanberg, MD
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Contacto:
- Clinical Trials Office
- Número de teléfono: 412-755-2930
- Correo electrónico: brodeurs@upmc.edu
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Rhode Island
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Providence, Rhode Island, Estados Unidos, 02903
- Reclutamiento
- Rhode Island Hospital
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Investigador principal:
- Ariel Birnbaum, MD
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Contacto:
- Brown Health Clinical Trials Office
- Número de teléfono: 401-444-5113
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South Carolina
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Charleston, South Carolina, Estados Unidos, 29425
- Reclutamiento
- Medical University of South Carolina, Hollings Cancer Center
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Contacto:
- Carly Fecio
- Número de teléfono: 8437923479
- Correo electrónico: fecio@musc.edu
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Investigador principal:
- John Kaczmar, MD
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Contacto:
- Número de teléfono: 843-792-9300
- Correo electrónico: nealli@musc.edu
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37232
- Reclutamiento
- Vanderbilt University Medical Center
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Investigador principal:
- Jennifer Choe, MD, PhD
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Contacto:
- Vanderbilt Clinical Research Center
- Número de teléfono: 615-322-2312
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Texas
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Houston, Texas, Estados Unidos, 77030
- Reclutamiento
- MD Anderson Cancer Center
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Contacto:
- Beryl Tross
- Número de teléfono: 713-745-0774
- Correo electrónico: bmtross@mdanderson.org
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Investigador principal:
- Van Morris, MD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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):
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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).
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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
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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.
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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.
• Expansion Cohort 6: Head and Neck Squamous Cell Carcinoma (HNSCC), metastatic or unresectable, recurrent with a Combined Positive Score (CPS) less than 1, as determined by PD-L1 IHC 22C3 pharmDx.
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Randomized to either ficerafusp alfa alone or in combination with pembrolizumab • Expansion Cohort 9: Colorectal cancer (CRC) i. Patients must have received at least 2 and no more than 3 prior lines of systemic therapy including two standard treatment regimens.
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: BCA101 Monotherapy
Route: IV Infusion Frequency: QW Current Dose: 1500mg |
EGFR/TGFβ fusion monoclonal antibody
Otros nombres:
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Experimental: BCA101 + pembrolizumab
Route: IV Infusion Frequency: Q3W Dose: 200mg |
EGFR/TGFβ fusion monoclonal antibody
Otros nombres:
anti-PD-1 |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs
Periodo de tiempo: 24 months
|
Incidence and severity of AEs and SAEs |
24 months
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Tolerability of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs
Periodo de tiempo: 24 months
|
Incidence and severity of AEs and SAEs |
24 months
|
|
Incidence of Dose Limiting Toxicities (DLTs)
Periodo de tiempo: 21 days
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Incidence of DLTs during the first cycle of treatment with BCA101 monotherapy or the combination of BCA101 and pembrolizumab. |
21 days
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Objective Response Rate
Periodo de tiempo: 24 months
|
Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST |
24 months
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Clinical Benefit Rate
Periodo de tiempo: 24 months
|
Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST |
24 months
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Progression free survival
Periodo de tiempo: 24 months
|
Determine PFS in each part of the study, per RECIST v1.1 and iRECIST |
24 months
|
|
Duration of Response
Periodo de tiempo: 24 months
|
Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST |
24 months
|
|
Overall Survival
Periodo de tiempo: 24 months
|
Determine survival rates in each part of the study. |
24 months
|
|
AUC of BCA101 and pembrolizumab
Periodo de tiempo: 24 months
|
AUC |
24 months
|
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Cmax of BCA101 and pembrolizumab
Periodo de tiempo: 24 months
|
Cmax |
24 months
|
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Tmax of BCA101 and pembrolizumab
Periodo de tiempo: 24 months
|
Tmax |
24 months
|
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Concentration vs time profile of BCA101 and pembrolizumab
Periodo de tiempo: 24 months
|
Ctrough |
24 months
|
|
Half-life of BCA101 and pembrolizumab
Periodo de tiempo: 24 months
|
Half-life |
24 months
|
|
Immunogenicity of BCA101 and pembrolizumab
Periodo de tiempo: 24 months
|
Incidence and titer of anti-drug-antibodies |
24 months
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Enfermedades Genitales
- Enfermedades del sistema endocrino
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Enfermedades intestinales
- Neoplasias por tipo histológico
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Neoplasias Intestinales
- Enfermedades Rectales
- Enfermedades Genitales Femeninas
- Neoplasias de glándulas endocrinas
- Enfermedades pancreáticas
- Neoplasias Glandulares y Epiteliales
- Enfermedades del Colon
- Enfermedades Ováricas
- Enfermedades anexiales
- Neoplasias Genitales Femeninas
- Trastornos gonadales
- Carcinoma
- Neoplasias De Células Escamosas
- Neoplasias Ováricas
- Carcinoma Epitelial De Ovario
- Carcinoma de células escamosas de cabeza y cuello
- Neoplasias colorrectales
- Carcinoma De Células Escamosas
- Neoplasias pancreáticas
- Neoplasias de Cabeza y Cuello
- pembrolizumab
Otros números de identificación del estudio
- BCA101X1101
- KEYNOTE-E28 (Otro identificador: Merck Sharp & Dohme LLC)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .