A Study of Sasanlimab in People With Non-muscle Invasive Bladder Cancer

EFS: time from randomization till recurrence of high-grade disease, progression of disease, persistence of carcinoma in situ (CIS), death due to any cause, whichever occurred first. Recurrence of high-grade disease: re-appearance of high-grade disease after randomization/study intervention initiation, re-appearance of high-grade disease after complete response (CR) for CIS participants or re-appearance of high-grade disease before CR for CIS participants and concurrent papillary disease at baseline. Progression of disease defined as any of following: Lamina propria invasion, muscle invasive disease, lymph node positive disease, metastatic disease, high-grade stage of bladder cancer (non-invasive papillary carcinoma [Ta] or invasion into the lamina propria without invasion into the muscularis propria [T1]) in participants with CIS only at baseline before achieving CR. Persistence of CIS: persistent CIS after induction, re-induction. EFS estimated using Kaplan-Meier analysis.

EFS: time from randomization till recurrence of high-grade disease, progression of disease, CIS, death due to any cause, whichever occurred first. Recurrence of high-grade disease: re-appearance of high-grade disease after randomization/study intervention initiation, re-appearance of high-grade disease after CR for CIS participants or re-appearance of high-grade disease before CR for CIS participants and concurrent papillary disease at baseline. Progression of disease defined as any of following: Lamina propria invasion, muscle invasive disease, lymph node positive disease, metastatic disease, high-grade stage of bladder cancer (non-invasive papillary carcinoma [Ta] or invasion into the lamina propria without invasion into the muscularis propria [T1]) in participants with CIS only at baseline before achieving CR. Persistence of CIS: persistent CIS after induction, re-induction. EFS estimated using Kaplan-Meier analysis.

Overall survival was defined as the time in months from the date of randomization to the date of death due to any cause. Participants last known to be alive will be censored at the date of last contact

Overall survival was defined as the time in months from the date of randomization to the date of death due to any cause. Participants last known to be alive will be censored at the date of last contact.

CR was defined as histologic disappearance of malignancy on bladder biopsy with negative cytology and cystoscopy or negative cytology and positive cystoscopy with biopsy-proven low-grade stage of bladder cancer defined as a non-invasive papillary carcinoma (Ta) lesion or non-malignant tissue for participants with CIS at randomization. 95% CI was based on Clopper-Pearson method.

Duration of CR was defined as the time from the first documentation of CR to the date of an EFS event for participants with CR. EFS was defined as the time in months from randomization until recurrence of high-grade disease, progression of disease, persistence of CIS or death due to any cause, whichever occurred first. CR was defined as histologic disappearance of malignancy on bladder biopsy with negative cytology and cystoscopy or negative cytology and positive cystoscopy with biopsy-proven low-grade stage of bladder cancer defined as a non-invasive papillary carcinoma (Ta) lesion or non-malignant tissue for participants with CIS at randomization. Kaplan-Meier method was used. 95% CI was estimated based on Brookmeyer and Crowley method.

Time to recurrence of low-grade disease was defined as the time from randomization to the date of first documentation of recurrence of low-grade disease. Recurrence of low-grade disease was defined as re-appearance of low-grade disease (low-grade Ta) after randomization based on positive biopsy, cystoscopy or cytology result. Kaplan-Meier method was used. 95% CI was estimated based on Brookmeyer and Crowley method.

Time to cystectomy was defined as time from randomization to cystectomy. Participants without a cystectomy will be censored at death date or last date known to be alive.

DSS was defined as the time from randomization to death resulting from bladder cancer, as assessed by the investigator. Participants last known to be alive will be censored at the date of last contact.

An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment up to 30 days after last dose of study treatment or 1 day before start day of new anti-cancer therapy.

An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment up to 30 days after last dose of study treatment or 1 day before start day of new anti-cancer therapy. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death or was life threatening or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant disability/incapacity, resulted in congenital anomaly/birth defect or other events.

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment up to 30 days after last dose of study treatment or 1 day before start day of new anti-cancer therapy. A SAE was any untoward medical occurrence at any dose that: resulted in death or was life threatening or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant disability/incapacity resulted in congenital anomaly/birth defect or other events. Relatedness was based on the investigator's judgement.

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment up to 30 days after last dose of study treatment or 1 day before start day of new anti-cancer therapy. NCI-CTCAE version 5.0, severity was graded as Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe and Grade 4 Life threatening and Grade 5: Death.

Laboratory parameters: hematocrit, hemoglobin, platelets, white blood cells, absolute neutrophil count, lymphocytes, monocytes, eosinophils, basophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium and bilirubin, blood urea nitrogen, urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus/phosphate, lipase, amylase, thyroid function test + reflex free thyroxine, free triiodothyronine, adrenocorticotropic hormone, international normalized ratio, partial thromboplastin time (PTT)/activated PTT, hepatitis B surface antigen, hepatitis C virus antibody. Severity grades per NCI-CTCAE v5.0: 1: Mild, 2: Moderate, 3: Severe, 4: Life threatening,5: Death.

The EORTC QLQ-C30 was a 30 self-administered questionnaire, which comprised of 5 functional domain subscales (physical functioning subscale, a role functioning subscale, an emotional functioning subscale, a cognitive functioning subscale and a social functioning subscale), 3 symptom scale (fatigue, pain, nausea and vomiting), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. All the scales and single-item measures range in score from 0 (poor functioning/no symptoms) to 100 (excellent functioning/greater degree of symptoms). Higher scores on functional domains indicated higher levels of functioning and higher scores on symptom scale/single items indicated greater presence of symptoms.

The EORTC QLQ NMIBC24 is a PRO developed and tested by the EORTC group specifically for participants with non-muscle invasive bladder cancer. The NMIBC24 has 24 items which can be grouped into 6 subscales: urinary symptoms (7 items), malaise (2 items), future worries (4 items), bloating/flatulence (2 items), sexual functioning (2 items), and male sexual issues (2 items). The NMIBC24 also assesses intravesical treatment, female sexual issues, sexual intimacy, risk of contaminating a partner, and sexual enjoyment (1 item each). All of the subscales and single-item measures range in score from 0 (poor functioning/no symptoms) to 100 (excellent functioning/greater degree of symptoms). Higher scores indicate greater impairment, except for sexual function and sexual enjoyment items, where higher scores indicate better function.

The PTAB questionnaire was a 2-item PRO designed to assess, from the participant perspective, any pain associated with the treatment administration and the burden of the amount of time required to complete the treatment administration procedures (1 item each). The items were scored on a range of 0 to 4, where 0=no pain/ not at all burdensome and 4= extremely severe pain/ extremely burdensome.

Concentration at Trough is defined as Predose/trough concentration Observed directly from data.

A participant was considered ADA (or NAb) positive if (1) baseline titer was missing or negative and participant had >= 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a >= 4-fold dilution increase in titer from baseline in >= 1 post-treatment sample (treatment-boosted).

PD-L1 expression was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and immune cells in regions of interest that were defined by tumor cell morphology. PDL-1 status was high if >=25% tumor cell or (immune cells present in the tumor area > 1% and PD-L1 positive immune cells+ >=25%) or (immune cells present in the tumor area = 1% and PD-L1 positive immune cells = 100%), and low if < 25% tumor cell and [(immune cells present in the tumor area > 1% and immune cells <25%) or (immune cells present in the tumor area = 1% and PD-L1 positive immune cells< 100%) or immune cells present = 0].