A Study of Atezolizumab With or Without Tiragolumab Following Neoadjuvant Chemoradiotherapy in Participants With Locally Advanced Rectal Cancer

NCT05009069 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: ML43050
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 5

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.

Conditions

Rectal Neoplasms; Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Pathological Complete Response (pCR)

  At Week 16, Day 1

Secondary Outcomes (8)

• Percentage of Participants With R0 Resection

  At Week 16, Day 1

• Objective Response Rate (ORR) Before Surgery

  At Week 16, Day 1

• One/Two/Three-year Relapse-free Survival (1/2/3-y RFS) Rate

  Year 1, Year 2, Year 3

• One/Two/Three-year Event-free Survival (1/2/3-y EFS) Rate

  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

Study Arms (2)

Atezolizumab + Tiragolumab

EXPERIMENTAL

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).

Radiation: Radiotherapy; Drug: Capecitabine; Drug: Fluorouracil; Drug: Atezolizumab; Drug: Tiragolumab

Atezolizumab

OTHER

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).

Radiation: Radiotherapy; Drug: Capecitabine; Drug: Fluorouracil; Drug: Atezolizumab

Interventions

Radiotherapy RADIATION

Weeks 1-5: 45-50.4Gy in 25-28 fractions to the pelvis on Days 1-5 every week.

Atezolizumab; Atezolizumab + Tiragolumab

Capecitabine DRUG

Weeks 1-5: Capecitabine 825 mg/m\^2 orally twice daily (bid) 5 days/week during radiotherapy.

Atezolizumab; Atezolizumab + Tiragolumab

Fluorouracil DRUG

Weeks 1-5: fluorouracil (5-FU) 225 mg/m\^2 intravenously (IV) over 24 hours 5 days/week during radiotherapy.

Atezolizumab; Atezolizumab + Tiragolumab

Atezolizumab DRUG

Weeks 8, 11 and 14: Atezolizumab 1200 mg IV on Day 1 of each 21-day cycle for 3 cycles.

Atezolizumab; Atezolizumab + Tiragolumab

Tiragolumab DRUG

Weeks 8, 11 and 14: Tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 3 cycles.

Atezolizumab + Tiragolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs for at least 5 months after the final dose of atezolizumab and for 90 days after the final dose of tiragolumab, for 6 months after the final dose of capecitabine, for 6 months after the final dose of 5-FU
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and agreement to refrain from donating sperm for at least 90 days after the final dose of tiragolumab, 3 months after final dose of capecitabine, for 6 months after the final dose of 5-FU.

You may not qualify if:

• 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
• Severe chronic or active infection within 4 weeks prior to initiation of study treatment
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled or symptomatic hypercalcemia

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (5)

Beijing Cancer Hospital

Beijing, 100142, China

Location

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, 510655, China

Location

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, 310009, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

First Hospital of China Medical University

Shenyang, 110001, China

Location

Related Publications (1)

• Tang W, Wu A, Lan P, Ding K, Wang Z, Wang J, Chen N, Wu X, Jiao Y, Liu F, Tong L, Shi Y, Xu J. Randomized Parallel-Group Phase II Study (NEOTERIC) of Atezolizumab With or Without Tiragolumab After Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer. J Clin Oncol. 2026 Mar;44(7):565-574. doi: 10.1200/JCO-25-01883. Epub 2026 Jan 13.

  PMID: 41529226 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiotherapy; Capecitabine; Fluorouracil; atezolizumab; Tiragolumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2021
• First Posted: August 17, 2021
• Study Start: March 18, 2022
• Primary Completion: November 21, 2023
• Study Completion (Estimated): November 10, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (5)