Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Atezolizumab · 2 trials · 8 indications
The number of local and regional SignateraTM ctDNA positive patients identified over 12 months in the setting of NED after all SOC definitive therapies (identified patients). This data will be obtained on a local and regional level through the SignateraTM company, Natera.
Percentage and absolute number of contacted patients who ultimately enrolled on trial (enrolled patients)
Percentage of patients in each cohort (and collectively) who achieve ctDNA CR (defined as ctDNA clearance on two sequential tests compared to baseline ctDNA and ongoing NED clinically/radiographically) within 12 weeks ± 14 days of study therapy.
Percentage of patients in each cohort (and collectively) who achieve ctDNA PR (ctDNA does not clear on two sequential tests, ctDNA does not double on each of two consecutive tests, does not increase on each of three consecutive tests, and ongoing NED clinically/radiographically) within 12 weeks ± 14 days of study therapy.
Rate of ctDNA POD or clinical/radiographic relapse is defined as the percentage of patients in each cohort (and collectively) who experience ctDNA doubling (at least) on each of two consecutive, sequential tests using the prior ctDNA value as the reference point for doubling for each test, ctDNA rise on each of three consecutive ctDNA tests using the prior ctDNA value as the reference point for each test (ctDNA POD), or clinical/radiographic relapse within 12 weeks ± 14 days of study therapy.
INV-DFS, defined as the time from randomization to the first occurrence of a DFS event, defined as any of the following: * Local (pelvic) recurrence of urothelial carcinoma (UC) (including soft tissue and regional lymph nodes); * Urinary tract recurrence of UC (including all pathological stages and grades); * Distant metastasis of UC; * Death from any cause.
| Arm | Type | Description |
|---|---|---|
| Atezolizumab plus Bevacizumab | EXPERIMENTAL | atezolizumab 1200 mg and bevacizumab 15 mg/kg given intravenously on Day 1 of each 21-day cycle (every 3 weeks \[Q3W\]) for a maximum of 12 months. |
| Arm A: Atezolizumab | EXPERIMENTAL | Atezolizumab will be administered intravenously (IV) at a dose of 1680 milligrams (mg) on Day 1 of each 28-day cycle for 12 cycles or up to 1 year (whichever occurs first). Atezolizumab will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor. |
| Arm B: Placebo | PLACEBO_COMPARATOR | Placebo will be administered IV on Day 1 of each 28-day cycle. Placebo will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor. Following the primary analysis, participants randomized to the comparator arm might discontinue placebo and may receive treatment outside the study at the investigator's discretion. |
| Arm C: Surveillance Follow-Up | EXPERIMENTAL | Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter surveillance follow-up. |
| Name | Type | Description |
|---|---|---|
| Atezolizumab | DRUG | Atezolizumab is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, |
| Bevacizumab | DRUG | Bevacizumab is a tumor-starving (anti-angiogenic) therapy. Avastin is designed to block a protein called vascular endothelial growth factor, or VEGF. |
| Placebo | OTHER | ctDNA positive participants will receive placebo IV, Q4W on Day 1 of each 28-day cycle |
| Signatera | DEVICE | Signatera will be used to evaluate whether ctDNA is detected during serial monitoring of peripheral blood samples for participants enrolled in surveillance. Participants with a ctDNA positive result will be screened for inclusion in the treatment phase. Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter surveillance follow-up. |
Inclusion Criteria: 1. Signed Informed Consent Form 2. Age \>= 18 years at time of signing Informed Consent Form 3. Ability to comply with the study protocol, in the investigator's judgment 4. Histologically or cytologically confirmed colorectal adenocarcinoma, gastric adenocarcinoma, pancreatic ad...