A Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Participants With Previously Untreated Locally Advanced Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer

Phase 2TerminatedNCT04832854

Hoffmann-La Roche50 enrolled

Overview

This study will evaluate the surgical safety and feasibility of atezolizumab plus tiragolumab alone or in combination with platinum-based chemotherapy as neoadjuvant treatment for participants with previously untreated locally advanced non-small cell lung cancer (NSCLC). The study will also evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of atezolizumab plus tiragolumab alone or in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by adjuvant atezolizumab plus tiragolumab or adjuvant platinum-based chemotherapy.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key inclusion criteria: * Histologically or cytologically confirmed Stage II, IIIA, or select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology * Eligible for R0 resection with curative intent at the time of screening * Adequate pulmonary function to be eligible for surgical resection with curative intent * Eligible to receive a platinum-based chemotherapy regimen * Measurable disease, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Availability of a representative tumor specimen that is suitable for determination of PD-L1 status * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Normal life expectancy, excluding lung cancer mortality risk * Adequate hematologic and end-organ function * Negative human immunodeficiency virus (HIV) test at screening * Negative serology for active hepatitis B virus (HBV) and active hepatitis C virus (HCV) at screening Key Exclusion Criteria: * NSCLC with histology of large cell neuroendocrine carcinoma, sarcomatoid carcinoma, or NSCLC not otherwise specified * Small cell lung cancer (SCLC) histology or NSCLC with any component of SCLC * Any prior therapy for lung cancer * Active or history of autoimmune disease or immune deficiency * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * Active tuberculosis * Significant cardiovascular disease * NSCLC with an activating EGFR mutation or ALK fusion oncogene * Known c-ros oncogene 1 (ROS1) rearrangement * History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with negligible risk of metastasis or death * Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety * Prior treatment with CD127 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-TIGIT, and anti-PD-L1 therapeutic antibodies * Treatment with systemic immunostimulatory agents * Treatment with systemic immunosuppressive medication * Pregnancy or breastfeeding

Locations (21)

City of Hope Cancer Center

Duarte, California, United States

University of Southern California

Los Angeles, California, United States

Washington University School of Medicine

St Louis, Missouri, United States

Winthrop Univ Hospital

Mineola, New York, United States

NYU Cancer Center

New York, New York, United States

Columbia University

New York, New York, United States

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Peter Maccallum Cancer Institute

Melbourne, Victoria, Australia

St. Vincent's Hospital

Gyeonggi-do, South Korea

Severance Hospital, Yonsei University Health System

Seoul, South Korea

...and 11 more locations

Outcomes

Primary Outcomes

Number of Participants With Surgical Delays

Participants were scheduled to undergo surgical resection of their tumor upon completion of four cycles of neo-adjuvant therapy. Prior to the surgery, the attending surgeon and medical oncologist assessed the participant to check if it was clinically feasible for them to undergo surgery (pre-surgical assessment). Surgery was to be done within 30 days of the pre-surgical assessment visit. Assessment of surgical delays were made by assessing the data entered in the electronic case report forms (eCRFs).

Time frame: Up to approximately 4.7 months

Number of Participants With Operative and Post-operative Complications

Participants who underwent surgical resection of their tumor and had intraoperative or post-operative complications were reported.

Time frame: From day of surgery up to end of safety follow-up (up to approximately 17.5 months)

Number of Participants With Surgical Cancellations Related to Study Treatment

Participants were scheduled to undergo surgical resection of their tumor upon completion of four cycles of neo-adjuvant therapy. Prior to the surgery, the attending surgeon and medical oncologist assessed the participant for to check if it was clinically feasible for them to undergo surgery (pre-surgical assessment). Surgery was to be done within 30 days of the pre-surgical assessment visit. Assessment of surgical delays were made by assessing the data entered in the eCRFs.

Time frame: Up to approximately 4.7 months

Number of Participants With Adverse Events (AEs)

AE=any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: Any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; Any new disease or exacerbation of an existing disease; Recurrence of an intermittent medical condition not present at baseline; Any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study treatment; AEs that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.

Time frame: From signing of informed consent to up to 90 days after the final dose of study treatment (Up to approximately 1.7 years)

Major Pathological Response (MPR) Rate

MPR rate was defined as the percentage of participants who achieved MPR. MPR was defined as ≤10% residual viable tumor at the time of surgical resection in the primary tumor, as assessed by the local pathology laboratory. Patients who did not proceed to surgery were considered as non-responders for MPR. 95% confidence interval (CI) was calculated using the Wilson Score Method. Percentages have been rounded off.

Time frame: At the time of surgical resection (From Day 114 to Day 144)

Secondary Outcomes

Percentage of Participants With Pathological Complete Response (pCR)

pCR was defined as the absence of any viable tumor cells in both the primary tumor and all sampled lymph nodes at the time of surgical resection, as assessed by local pathology laboratory. 95% CI was calculated using the Wilson Score Method. Percentages have been rounded off.

Time frame: At the time of surgical resection (From Day 114 to Day 144)

Event-free Survival (EFS)

EFS was defined as the time from first dose of the study drug to any of the following events, whichever occurs first: disease progression that precludes surgery, as assessed by the investigator; local or distant disease recurrence (including occurrence of new primary NSCLC); or death from any cause. Median was estimated using Kaplan-Meier (K-M) method. 95% CI for median was computed using the method of Brookmeyer and Crowley.

Time frame: Up to approximately 3.8 years

Serum Concentrations of Atezolizumab at Specified Timepoints

Time frame: Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12, and 16; 30 minutes (min) post-infusion Day 1 of Cycle 1; (Cycle=21 days)

Serum Concentrations of Tiragolumab at Specified Timepoints

Time frame: Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12, 16; 30 minutes (min) post-infusion Cycle 1 Day 1; (Cycle=21 days)

Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab

Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). Percentages have been rounded off.

Time frame: Up to approximately 3.8 years

Percentage of Participants With ADAs to Tiragolumab

Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following tiragolumab exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). Percentages have been rounded off.