Locally Advanced or Metastatic Urothelial Carcinoma
Conditions
Keywords
Avelumab, Avelumab in combination, Bladder cancer, M6223 (anti-TIGIT antibody), PD-L1, Sacituzumab govitecan (Trop-2 antibody drug conjugate), NKTR-255 (IL-15 agonist)
Brief summary
The purpose of this study is to assess the safety and efficacy of avelumab in combination with other anti-tumor agents as a maintenance treatment in participants with bladder cancer.
Interventions
DRUGAvelumab
Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment.
DRUGSacituzumab Govitecan
Participants will receive sacituzumab govitecan intravenous infusion at dose of 10 milligrams per kilogram (mg/kg) of body weight once a week (Q1W) on Day 1 and 8 of 21-day treatment cycles, in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.
DRUGM6223
Participants will receive M6223 (anti-T cell-immuno-receptor with Ig and ITM domains \[anti-TIGIT\]) intravenous infusion at dose of 1600 mg Q2W in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.
DRUGNKTR-255
Participants will receive NKTR-255 intravenous infusion at a dose of 3 micrograms per kilogram body weight (mcg/kg) once every 4 weeks (Q4W) in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with histologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma. Both transitional cell and mixed transitional/non- transitional cell histologies are allowed, but transitional cell carcinoma must be the predominant histology * Participants has documented Stage IIIA/IIIB with N1-N3, or Stage IV disease (per American Joint Committee on Cancer/International Union for Cancer Control Tumor Node Metastasis system, 8th edition) at the start of first line chemotherapy. * The last dose of first line chemotherapy must have been received no less than 4 weeks, and no more than 10 weeks, prior to randomization in the present study * Estimated life expectancy of at least 3 months * Participants without progressive disease as per RECIST v1.1 guidelines following completion of 4 to 6 cycles of 1L chemotherapy. Eligibility based on this criterion will be determined by Investigator review of pre chemotherapy and post chemotherapy radiological assessments (CT/MRI scans). * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 * Adequate hematological, hepatic, and renal function as defined in the protocol * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Participants with prior immunotherapy with Interleukin-2 (IL-2), IL-15, interferon alfa (IFN-α), or an anti programmed death receptor-1 (PD-1), anti programmed death-ligand 1 (PD-L1), anti PD-L2, anti CD137, or cytotoxic T cell lymphocyte-4 (CTLA-4) antibody (including ipilimumab), anti TROP2, anti-T-cell-immuno-receptor with Ig and ITM domains (anti-TIGIT) any other antibody or drug specifically targeting T cell costimulation or immune checkpoint pathways, agents targeting Nectin-4, or any of the investigational drugs used in combination with avelumab. * Participants with active infection 48 hours before randomization requiring systemic therapy * Participants with known prior or suspected hypersensitivity to study drugs or any component in their formulations * Participants with prior adjuvant or neoadjuvant systemic therapy within 12 months of randomization * Participants with vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines) administered \>= 2 weeks prior first dose of study treatment. All severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccines approved or authorized by local Health Authorities are allowed * Other protocol defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator | Time from randomization of study drug until first documentation of progressive disease (PD) or death, assessed approximately up to 51 months |
| Number of Participants with Treatment Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, and AEs of Special Interest (AESIs) as per Qualitative Toxicity Scale [National Cancer Institute-Common Terminology Criteria for Adverse Events 5.0] | From Randomization up to the last safety follow-up visit at approximately up to 51 months |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) | Time from randomization of study drug until death, assessed approximately up to 51 months |
| Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator | Time from randomization of study drug up to 51 months |
| Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator | Time from first documented objective response to PD or death due to any cause, assessed approximately up to 51 months |
| Pharmacokinetic Serum Concentration of Avelumab, M6223, Sacituzumab govitecan and NKTR255 | Pre-dose up to safety follow up, assessed approximately up to maximum 51 months |
| Number of Participants with Positive Anti-Drug Antibody (ADA) of Avelumab, M6223, Sacituzumab govitecan and NKTR-255 | Baseline up to 51 months |
| Change From Baseline in National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Disease Related Symptoms-Physical Subscale (DRS-P) Scores | Baseline, Week 13 |
Countries
Australia, Belgium, Canada, France, Germany, Greece, Italy, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Responsible
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Outcome results
None listed