A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)

Condition(s) studied

Investigational drug(s) / intervention(s)

Avelumab: Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Sacituzumab Govitecan (SG): Participants received intravenous infusion SG at dose of 10 mg/kg of bodyweight once a week on Day 1 and 8 of each 21-daytreatment cycles until unacceptable toxicity, withdraw consent or initiation of a new treatment.

M6223: Participants intravenous infusion of M6223 at dose of 1600 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.

NKTR-255: Participants intravenous infusion of NKTR-255 at a dose of 3 mcg/kg of body weight once every 4 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.

JB100: As per the Clinical Study Protocol, the control group (avelumab alone) was extended by data from an external control, i.e. the JAVELIN Bladder 100 study (JB100) (NCT02603432). Participants received an intravenous infusion of 10 mg/kg of Avelumab along with best supportive care (BSC), on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered asper the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anticancer therapy.

Study 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.

Eligibility

Primary outcome measure(s)

• Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator - Avelumab + Sacituzumab Govitecan Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control]) — Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
  PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions. The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times. PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm. PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
• Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator - Avelumab + M6223 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control]) — Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
  PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions. The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times. PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm. PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
• Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator - Avelumab + NKTR-255 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control]) — Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
  PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions. The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times. PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm. PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, and AEs of Special Interest (AESIs) — Up to 32 months and 12 days (Current study) and 61 months and 11 days (JB100 extended control group)
  Adverse Event (AE): any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as events with onset date or worsening during the on-treatment period, defined as the time from the first dose of study intervention administration days to the last administration day + 30 days, or the start day of subsequent anticancer therapy - 1 day, whichever occurred first. TEAEs included serious AEs and non- serous AEs. AESIs included Infusion-related reactions (IRRs), Immune-related AEs (irAEs), Thromboembolic events, Cytokine release syndrome, QT interval prolongation.

Trial sites (98)

+ 58 more sites — see the full list on the official registry below.

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