| Titre |
A Phase 2 Multi-Cohort, Open-Label, Multi-Center Clinical Study Evaluating the Efficacy and Safety of Disitamab Vedotin (RC48-ADC) Alone and in Combination With Pembrolizumab in Subjects With Locally-Advanced Unresectable or Metastatic Urothelial Carcinoma That Expresses HER2 |
| Protocole ID |
KEYNOTE-D78 |
| ClinicalTrials.gov ID |
NCT04879329 |
| Type(s) de cancer |
Vessie/urothélial |
| Phase |
Phase II |
| Stade |
Maladie avancée ou métastatique |
| Type étude |
Clinique |
| Médicament |
Disitamab vedotin seul et en association avec le pembrolizumab |
| Institution |
CIUSSS DE L'ESTRIE – CENTRE HOSP. UNIV. DE SHERBROOKE
 HOPITAL FLEURIMONT
3001 12e Avenue Nord, Sherbrooke, QC, J1H 5N4
|
| Ville |
Sherbrooke |
| Investigateur(trice) principal(e) |
Dr Michel Pavic
|
| Coordonnateur(trice) |
Anick Champoux
819-346-1110 poste 12811
|
| Statut |
 Actif en recrutement |
| Date d'activation |
10-02-2023 |
| Critètes d'éligibilité |
Cohorts A and B (***la cohorte B est fermée au recrutement en date du 15 mars 2024***)
- 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 2 or 3 prior lines of systemic therapy for LA/mUC, including the following:
- 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.
- Participants with available tissue should provide archived or freshly sectioned slides
- 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
|
| Critètes d'exclusion |
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
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)
- 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
There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.
|
Groupe d'étude en oncologie du Québec