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

OS: time from date of randomization to death. OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates. PS were used as weights to minimize the impact of confounding factors on the 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 the sum of weights adding up to number of participants in randomized control arm. Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates. OS 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.

OS: time from date of randomization to death. OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates. PS were used as weights to minimize the impact of confounding factors on the 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 the sum of weights adding up to number of participants in randomized control arm. Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates. OS 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.

OS: time from date of randomization to death. OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates. PS were used as weights to minimize the impact of confounding factors on the 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 the sum of weights adding up to number of participants in randomized control arm. Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates. OS 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.

ORR is defined as percentage of participants who achieved either a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1 from randomization to first observation of progression disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

ORR is defined as percentage of participants who achieved either a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1 from randomization to first observation of progression disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

ORR is defined as percentage of participants who achieved either a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1 from randomization to first observation of progression disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

DoR was defined as time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to PD or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

DoR was defined as time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to PD or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

DoR was defined as time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to PD or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

Serum concentrations of Avelumab were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".

Serum concentrations of Avelumab in investigational arm (Avelumab + Sacituzumab Govitecan (SG) were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".

Serum concentrations of Avelumab in investigational arm (Avelumab + M6623) were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day"

Serum concentrations of Avelumab in investigational arm (Avelumab + NKTR-255) were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".

Serum concentrations of SG were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".

Serum concentrations of M6223 were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".

Serum concentrations of NKTR-255 were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".

Number of participants with positive ADA of Avelumab and combination drugs (Sacituzumab Govitecan [SG], M6223 and NKTR-255) were reported.

The NCCN FACT FBlSI-18 is designed to be a stand-alone instrument to measure symptoms and quality of life in participants with urothelial carcinoma and was created using inputs from participants and oncologists. The disease-related symptoms - physical (DRS-P) subscale uses a subset of physical symptoms which are specific to urothelial carcinoma, i.e., pain, weight loss, urination, weakness, dizziness, meeting family needs, appetite, erection in males, and sleep. Each question offers 5 answers: not at all (0), a little bit (1), somewhat (2), quite a bit (3), very much (4). The overall summary range is 0-36. The scores of negatively stated items (e.g., pain) are reversed and added together with the positively stated scores. The sum of these item scores are multiplied by the number of items in the subscale, i.e., by 9, and divided by the number of items answered. In general, higher scores are better than lower scores.

The NCCN FACT FBlSI-18 is designed to be a stand-alone instrument to measure symptoms and quality of life in participants with urothelial carcinoma and was created using inputs from participants and oncologists. The disease-related symptoms - physical (DRS-P) subscale uses a subset of physical symptoms which are specific to urothelial carcinoma, i.e., pain, weight loss, urination, weakness, dizziness, meeting family needs, appetite, erection in males, and sleep. Each question offers 5 answers: not at all (0), a little bit (1), somewhat (2), quite a bit (3), very much (4). The overall summary range is 0-36. The scores of negatively stated items (e.g., pain) are reversed and added together with the positively stated scores. The sum of these item scores are multiplied by the number of items in the subscale, i.e., by 9, and divided by the number of items answered. In general, higher scores are better than lower scores.

The NCCN FACT FBlSI-18 is designed to be a stand-alone instrument to measure symptoms and quality of life in participants with urothelial carcinoma and was created using inputs from participants and oncologists. The disease-related symptoms - physical (DRS-P) subscale uses a subset of physical symptoms which are specific to urothelial carcinoma, i.e., pain, weight loss, urination, weakness, dizziness, meeting family needs, appetite, erection in males, and sleep. Each question offers 5 answers: not at all (0), a little bit (1), somewhat (2), quite a bit (3), very much (4). The overall summary range is 0-36. The scores of negatively stated items (e.g., pain) are reversed and added together with the positively stated scores. The sum of these item scores are multiplied by the number of items in the subscale, i.e., by 9, and divided by the number of items answered. In general, higher scores are better than lower scores.