Resumen

Este estudio se realiza para evaluar si un fármaco denominado disitamab vedotín, solo o combinado con pembrolizumab, resulta eficaz para tratar el cáncer urotelial con expresión de HER2. También se evaluará la seguridad del fármaco en los participantes. Los participantes presentarán un cáncer que se ha diseminado en el organismo en la zona de origen (localmente avanzado) y que no puede extirparse (irresecable) o que se ha diseminado a distancia (metastásico). Asimismo, se estudiarán los efectos adversos que se producen cuando los participantes reciben el fármaco. Un efecto adverso es cualquier efecto que produce un fármaco en el organismo más allá del tratamiento de la enfermedad.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Cohorts A and B
Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra
Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy
At least one measurable lesion by investigator assessment based on RECIST version 1.1.
HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
Cohort C
Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra
No prior systemic therapy for LA/mUC
Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy
At least one measurable lesion by investigator assessment based on RECIST v1.1.
Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation
HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, on the provided tumor tissue sample
ECOG performance status of 0, 1, or 2
Cohort D
Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra
Based on a participant's eligibility to receive treatment with standard of care therapies in Japan, participants must have received all of the following lines of therapy for LA/mUC:
a. One prior line of platinum-containing chemotherapy.
b. Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second line treatment.
c. Prior enfortumab vedotin therapy.
At least one measurable lesion by investigator assessment based on RECIST v1.1.
ECOG performance status of 0 or 1
Cohort E
Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra
No prior systemic therapy for LA/mUC
Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy.
At least one measurable lesion by investigator assessment based on RECIST v1.1.
Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation
HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
ECOG performance status of 0 or 1
Cohort G
Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra
Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of therapy containing enfortumab vedotin as monotherapy or in combination with pembrolizumab
The last administration of enfortumab vedotin must be 90 days from the start of study treatment. Intervening therapies are allowed between the final dose of enfortumab vedotin and the start of disitamab vedotin.
At least one measurable lesion by investigator assessment based on RECIST version 1.1.
HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Criterios de exclusión

Cohorts A and B
Known hypersensitivity to disitamab vedotin or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohorts A and B)
Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
Major surgery that has not fully recovered within 4 weeks prior to dose administration
Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline
Cohort C
Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study defined as Cycle 1 Day 1 for the single-arm part of Cohort C and as randomization date for the randomized part of Cohort C)
Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
Major surgery that has not fully recovered within 4 weeks prior to dose administration
Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
Participants who have previously received any prior treatment with an agent directed to another stimulatory or co-inhibitory T cell receptor (including but not limited to CD137 agonists, CAR-T cell therapy, CTLA-4 inhibitors, or OX-40 agonists) are excluded.
Cohort D
Known hypersensitivity to disitamab vedotin or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort D)
Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
Prior HER2-directed therapy
Any prior history of ≥ Grade 3 non-hematological AEs related to prior therapy
Major surgery that has not fully recovered within 4 weeks prior to dose administration
Peripheral sensory or motor neuropathy ≥ Grade 1 at baseline
Cohort E
Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort E)
Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
Any prior history of ≥ Grade 3 non-hematological AEs related to prior therapy
Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
Major surgery that has not fully recovered within 4 weeks prior to dose administration
Peripheral sensory or motor neuropathy ≥ Grade 1 at baseline
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
Cohort G
Known hypersensitivity to disitamab vedotin or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort G)
Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
Prior HER2-directed therapy
Major surgery that has not fully recovered within 4 weeks prior to dose administration
Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline

Ubicaciones

Centro de Investigaciones Médicas y Desarrollo LC S.R.L

Buenos Aires, Buenos Aires F.D., Argentina

ACTIVE_NOT_RECRUITING

Clinica Viedma

Viedma, Río Negro Province, Argentina

RECRUITING

Hospital Aleman

Buenos Aires, Argentina

RECRUITING

Instituto Medico Especializado Alexander Fleming

Buenos Aires, Argentina

RECRUITING

Hospital Sirio Libanes - Buenos Aires

Buenos Aires, Argentina

RECRUITING

Centro Medico Austral

CABA, Argentina

RECRUITING

Centro Oncologico Korben

Caba, Argentina

RECRUITING

Instituto Oncologico de Cordoba

Córdoba, Argentina

RECRUITING

Estudio clínico de fase 2, multicohort, abierto y multicéntrico para evaluar la eficacia y seguridad de disitamab vedotín (RC48-ADC) solo o en combinación con pembrolizumab en sujetos con carcinoma urotelial localmente avanzado irresecable o metastásico que expresa HER2

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

disitamab vedotin

pembrolizumab

Ubicaciones

Centro de Investigaciones Médicas y Desarrollo LC S.R.L

Clinica Viedma

Hospital Aleman

Instituto Medico Especializado Alexander Fleming

Hospital Sirio Libanes - Buenos Aires

Centro Medico Austral

Centro Oncologico Korben

Instituto Oncologico de Cordoba

Patrocinadores

Contactos

Pfizer CT.gov Call Center