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

Roche

Status and phase

Active, not recruiting

Phase 2

Conditions

Rectal Neoplasms

Rectal Cancer

Treatments

Drug: Fluorouracil

Drug: Tiragolumab

Radiation: Radiotherapy

Drug: Atezolizumab

Drug: Capecitabine

Study type

Interventional

Funder types

Industry

Identifiers

NCT05009069

ML43050

Details and patient eligibility

About

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.

Enrollment

58 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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
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.

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
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
Uncontrolled diabetes or Grade ≥ 2 abnormalities in potassium, sodium, despite standard medical management within 14 days prior to initiation of study treatment
Prior treatment with CD137 agonists, T-cell co-stimulating, or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-TIGIT therapeutic antibodies
Treatment with systemic immunostimulatory agents
Treatment with systemic immunosuppressive medication
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
Major surgical procedure or significant traumatic injury within 28 days prior to initiation of study treatment, or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study treatment
Any other disease, medical condition or abnormality, metabolic dysfunction, alcohol or drug abuse or dependence, physical examination finding, clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk from treatment complications
Treatment with any other investigational agent with therapeutic intent within 28 days prior to study treatment initiation
History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
History of allergic reactions to chemotherapy drugs (5-FU and capecitabine)
Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to fluoropyrimidine therapy in participants selected to receive capecitabine
Pregnant or breastfeeding

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

58 participants in 2 patient groups

Atezolizumab + Tiragolumab

Experimental group

Description:

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).

Treatment:

Drug: Capecitabine

Drug: Atezolizumab

Radiation: Radiotherapy

Drug: Tiragolumab

Drug: Fluorouracil

Atezolizumab

Other group

Description:

Treatment:

Drug: Capecitabine

Drug: Atezolizumab