A Phase II, Randomized, Open Label, Parallel-group Study of Atezolizumab With or Without Tiragolumab Following Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Radiotherapy
- Conditions
- Rectal Neoplasms
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 58
- Locations
- 10
- Primary Endpoint
- Percentage of Participants With Pathological Complete Response (pCR)
- Status
- Active, not recruiting
- Last Updated
- 11 days ago
Overview
Brief Summary
This study will evaluate the efficacy and safety of atezolizumab plus tiragolumab or atezolizumab alone following neoadjuvant chemoradiotherapy (nCRT) in participants with locally advanced rectal cancer (LARC). The study consists of a safety run-in phase and a randomization phase. Participants enrolled in the safety run-in phase will receive atezolizumab + tiragolumab following nCRT. Upon determination of the safety of the treatment regimen, the study will be proceed to the randomization phase. Participants will be randomized in a 1:1 ratio to the atezolizumab + tiragolumab arm or atezolizumab arm.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed diagnosis of adenocarcinoma of the rectum
- •Resectable locally advanced rectal cancer, with clinical stage as cT3N+M0 or cT4NanyM0 per American Joint Committee on Cancer (AJCC)/ International Union Against Cancer (UICC) 8th edition
- •The inferior margin of the tumor ≤10cm from the anal verge
- •No prior anti-cancer treatment for rectal cancer
- •Availability of a representative tumor specimen that is suitable for pathological evaluation and biomarker expression analysis
- •Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 or 1
- •At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RESIST) v1.1
- •Adequate hematologic and end-organ function
- •For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- •Negative HIV test at screening
Exclusion Criteria
- •Evidence of metastatic disease
- •Histology consistent with small cell carcinoma, squamous carcinoma, or mixed carcinoma
- •Presence of synchronous colorectal cancer
- •Presence of obstruction or imminent obstruction
- •Clinical symptoms or radiological suspicion of bowel perforation
- •Not eligible for long-course radiotherapy
- •History of malignancies other than rectal cancer within 3 years prior to screening with the exception of those with a negligible risk of metastasis or death
- •Active or history of autoimmune disease or immune deficiency
- •Significant cardiovascular disease
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
Arms & Interventions
Atezolizumab + Tiragolumab
Weeks 1-5: Radiotherapy to the pelvis on Days 1-5 every week. Chemotherapy: Capecitabine or fluorouracil (5-FU) 5 days/week during radiotherapy. Day 1 of Weeks 8, 11 and 14: Atezolizumab plus tiragolumab (Day 1 of each 21-day cycle for 3 cycles).
Intervention: Radiotherapy
Atezolizumab + Tiragolumab
Weeks 1-5: Radiotherapy to the pelvis on Days 1-5 every week. Chemotherapy: Capecitabine or fluorouracil (5-FU) 5 days/week during radiotherapy. Day 1 of Weeks 8, 11 and 14: Atezolizumab plus tiragolumab (Day 1 of each 21-day cycle for 3 cycles).
Intervention: Fluorouracil
Atezolizumab + Tiragolumab
Weeks 1-5: Radiotherapy to the pelvis on Days 1-5 every week. Chemotherapy: Capecitabine or fluorouracil (5-FU) 5 days/week during radiotherapy. Day 1 of Weeks 8, 11 and 14: Atezolizumab plus tiragolumab (Day 1 of each 21-day cycle for 3 cycles).
Intervention: Atezolizumab
Atezolizumab
Weeks 1-5: Radiotherapy to the pelvis on Days 1-5 every week. Chemotherapy: Capecitabine or fluorouracil (5-FU) 5 days/week during radiotherapy. Day 1 of Weeks 8, 11 and 14: Atezolizumab (Day 1 of each 21-day cycle for 3 cycles).
Intervention: Radiotherapy
Atezolizumab + Tiragolumab
Weeks 1-5: Radiotherapy to the pelvis on Days 1-5 every week. Chemotherapy: Capecitabine or fluorouracil (5-FU) 5 days/week during radiotherapy. Day 1 of Weeks 8, 11 and 14: Atezolizumab plus tiragolumab (Day 1 of each 21-day cycle for 3 cycles).
Intervention: Capecitabine
Atezolizumab + Tiragolumab
Weeks 1-5: Radiotherapy to the pelvis on Days 1-5 every week. Chemotherapy: Capecitabine or fluorouracil (5-FU) 5 days/week during radiotherapy. Day 1 of Weeks 8, 11 and 14: Atezolizumab plus tiragolumab (Day 1 of each 21-day cycle for 3 cycles).
Intervention: Tiragolumab
Atezolizumab
Weeks 1-5: Radiotherapy to the pelvis on Days 1-5 every week. Chemotherapy: Capecitabine or fluorouracil (5-FU) 5 days/week during radiotherapy. Day 1 of Weeks 8, 11 and 14: Atezolizumab (Day 1 of each 21-day cycle for 3 cycles).
Intervention: Capecitabine
Atezolizumab
Weeks 1-5: Radiotherapy to the pelvis on Days 1-5 every week. Chemotherapy: Capecitabine or fluorouracil (5-FU) 5 days/week during radiotherapy. Day 1 of Weeks 8, 11 and 14: Atezolizumab (Day 1 of each 21-day cycle for 3 cycles).
Intervention: Fluorouracil
Atezolizumab
Weeks 1-5: Radiotherapy to the pelvis on Days 1-5 every week. Chemotherapy: Capecitabine or fluorouracil (5-FU) 5 days/week during radiotherapy. Day 1 of Weeks 8, 11 and 14: Atezolizumab (Day 1 of each 21-day cycle for 3 cycles).
Intervention: Atezolizumab
Outcomes
Primary Outcomes
Percentage of Participants With Pathological Complete Response (pCR)
Time Frame: At Week 16, Day 1
Secondary Outcomes
- One/Two/Three-year Event-free Survival (1/2/3-y EFS) Rate(Year 1, Year 2, Year 3)
- Percentage of Participants With R0 Resection(At Week 16, Day 1)
- 1/2/3-y EFS Rate in Subgroup Population With PD-L1/ PVR/TIGIT Positive Expression(Year 1, Year 2, Year 3)
- Percentage of Participants With pCR in Subgroup Population With PD-L1/ PVR/TIGIT Positive Expression(At Week 16, Day 1)
- Percentage of Participants With Adverse Events(Up to 40 months)
- One/Two/Three-year Relapse-free Survival (1/2/3-y RFS) Rate(Year 1, Year 2, Year 3)
- Objective Response Rate (ORR) Before Surgery(At Week 16, Day 1)
- 1/2/3-y Disease-free Survival (DFS) Rate in Subgroup Population With PD-L1/ PVR/TIGIT Positive Expression(Year 1, Year 2, Year 3)