Atezolizumab Immunotherapy With or Without Tiragolumab for Patients With Unresectable Stage III NSCLC

NCT05798663 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AFT-57
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 15

Brief Summary

This is a phase II trial of neoadjuvant and adjuvant atezolizumab with or without tiragolumab in conjunction with chemoradiotherapy for unresectable stage III NSCLC.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• To determine the progression-free survival (PFS) of patients treated with neoadjuvant, concurrent and adjuvant atezolizumab with or without tiragolumab.

  The primary objective is to determine the relative efficacy of atezolizumab with or without tiragolumab based on progression-free survival (PFS) and select a promising treatment out of the two experimental regiments for further investigation in a future phase III trial compared with standard of care treatment. Progression-Free Survival (PFS) is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.

  2 years

Secondary Outcomes (3)

• Overall survival (OS)

  2 years

• overall response (ORR)

  2 years

• Safety of the two regimens

  1 year

Study Arms (3)

Arm A: Atezolizumab

EXPERIMENTAL

79 participants will be randomized 1:1 to Arm A. Participants in Arm A will receive induction immunotherapy with atezolizumab on Day 1 of each cycle, concurrent chemoradiotherapy, and adjuvant atezolizumab Day 1 of each cycle.

Drug: Atezolizumab

Arm B: Atezolizumab and Tiragolumab

EXPERIMENTAL

79 participants will be randomized 1:1 to Arm B. Participants in Arm B will receive induction immunotherapy with atezolizumab plus tiragolumab on Day 1 of each cycle, concurrent chemoradiotherapy, and adjuvant atezolizumab plus tiragolumab on Day 1 of each cycle.

Drug: Atezolizumab; Drug: Tiragolumab

Arm C: Atezolizumab and Tiragolumab

EXPERIMENTAL

An additional pilot cohort of 20 patients will be accrued at selected sites towards the end of the overall accrual period and after initial safety evaluations of the addition of tiragolumab to atezolizumab before and after chemoradiotherapy. Participants enrolled to Arm C will receive induction immunotherapy with atezolizumab plus tiragolumab on Day 1 of each cycle, concurrent atezolizumab plus tiragolumab with chemoradiotherapy, and adjuvant atezolizumab plus tiragolumab on Day 1 of each 21 cycle.

Drug: Atezolizumab; Drug: Tiragolumab

Interventions

Atezolizumab DRUG

Atezolizumab will be given to participants either intravenously at a dosage of 1200mg or subcutaneously at a dosage of 1875 mg on Day 1 of each 21-day cycle for Arms A, B, and C, and on days 1 and 22 of concurrent chemoradiotherapy for Arm C only.

Also known as: Tecentriq, L01XC32

Arm A: Atezolizumab; Arm B: Atezolizumab and Tiragolumab; Arm C: Atezolizumab and Tiragolumab

Tiragolumab DRUG

Tiragolumab will be given to participants intravenously at a dosage of 600 mg on day 1 of each 21-day cycle (Arms B and C), and on days 1 and 22 of concurrent chemoradiotherapy (Arm C only).

Arm B: Atezolizumab and Tiragolumab; Arm C: Atezolizumab and Tiragolumab

Eligibility Criteria

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

You may qualify if:

• Newly pathologically proven diagnosis of stage IIIA/B/C (per AJCC 8) NSCLC
• Age at least 18 years.
• Availability of a representative tumor specimen that is suitable for BOTH determination of PD-L1 status via local testing and, independently, other required correlative study biomarkers. Tissue submission should include:
• A representative FFPE tumor specimen in a paraffin block, along with an associated pathology report, which will be sent to the biorepository. If institutional policy prevents the submission of a block, refer to the Correlative Science Manual (CSM) for alternative submission instructions.
• If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening. Questions about biopsy adequacy should be directed to the study team.
• Patients may still be eligible after these two points (3a and 3b) have been attempted/considered, at the discretion of the AFT Study Team.
• No active autoimmune disease or uncontrolled infection
• FEV1 ≥ 1.2L or \> 40% predictive
• No underlying heart or lung disease precluding treatment per protocol.
• Measurable (RECIST v1.1) stage IIIA, IIIB or IIIC disease per AJCC 8.
• Patients must be considered unresectable or inoperable. Patients who decline surgery for stage III NSCLC are also eligible. Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the following criteria are met:
• No prior systemic therapy or radiation for this lung cancer
• Prior curative-intent surgery at least 3 months prior to the nodal recurrence Note: Patients may be medically unfit for surgery, (e.g., due to general anesthesia risk), but remain fit for chemoradiotherapy. Thus, the criterion does not necessarily have to exclude all patients who are medically unfit for surgery.
• Stage III A/B/C disease (per AJCC 8) with minimum diagnostic evaluation to include:
• History/physical examination within 4 weeks

You may not qualify if:

• Active autoimmune disease.
• Greater than minimal, exudative, or cytologically positive pleural effusions.
• Involved contralateral hilar nodes.
• More than 10% unintentional weight loss within the past month.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the breast, localized prostate cancer or thyroid nodules, carcinoma in situ of the oral cavity or cervix are all permissible.
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable.
• Prior radiotherapy to the region of the study cancer that would result in clinically significant overlap of radiation therapy fields.
• Prior severe infusion reaction to a monoclonal antibody.
• Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within the last 6 months, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration or within 2 weeks of cycle 1 day 1.
• Severe active infection, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact patient safety
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration.
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.

Sponsors & Collaborators

• Alliance Foundation Trials, LLC.: lead
• Genentech, Inc.: collaborator

Study Sites (15)

University of California San Diego Moores Cancer Center

La Jolla, California, 92037, United States

Location

Kaiser Permanente Oakland Medical Center

Oakland, California, 94611, United States

Location

Kaiser Permanente Roseville Medical Center

Roseville, California, 95661, United States

Location

Kaiser Permanente San Francisco Medical Center

San Francisco, California, 94115, United States

Location

Kaiser Permanente Santa Clara Medical Center

Santa Clara, California, 95051, United States

Location

Kaiser Permanente Vallejo Medical Center

Vallejo, California, 94589, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Washington University Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Missouri Baptist Medical Center

St Louis, Missouri, 63131, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

New Hampshire Oncology - Hematology, PA

Manchester, New Hampshire, 03103, United States

Location

Hematology Oncology Associates of Central New York, P.C.

East Syracuse, New York, 13057, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

atezolizumab; Tiragolumab

Study Officials

• Helen Ross, MD

  Rush University

  STUDY CHAIR

• Evanthia Galanis, MD

  Alliance Foundation Trials, LLC.

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 23, 2023
• First Posted: April 4, 2023
• Study Start: December 7, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: October 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)