Prospective, non-randomized, open-label, single-arm phase II trial to investigate the feasibility and efficacy of combining chemotherapy with tiragolumab and atezolizumab as neoadjuvant and adjuvant treatment for surgical NSCLC patients.
The present study is a prospective, investigator-initiated, single-arm, open-label phase II trial. Patients with non-small cell lung cancer of clinical stage II, IIIA and IIIB (T3N2 only) will receive 2 cycles platinum-based standard of care chemotherapy in combination with anti-TIGIT antibody tiragolumab and the anti-PD-L1 antibody atezolizumab followed by curative intent surgery. After surgery, patients not achieving pCR will receive additional 2 cycles chemotherapy in combination with tiragolumab and atezolizumab, followed by tiragolumab/atezolizumab only for up to one year (max 16 cycles) or until intolerable toxicity, disease progression or patients' request, whatever occurs first. Patients with pCR will receive the IO-IO antibodies only (without additional chemotherapy). The objective of this study is to investigate the feasibility, efficacy and safety of combining chemotherapy with tiragolumab and atezolizumab as neoadjuvant and adjuvant treatment for surgical NSCLC patients. Efficacy outcomes will be correlated to the accompanying in-depth translational analyses, which aim to understand the role of the tumor microenvironment in response to IO-IO therapies and to identify biomarkers that may be associated with response and resistance.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Atezolizumab 1,200 mg by IV infusion Q3W.
Tiragolumab by IV infusion Q3W.
Universitätsklinikum Essen (AöR)-Westdeutsches Tumorzentrum Essen
Essen, Germany
Thoraxklinik Heidelberg
Heidelberg, Germany
MPR rate after curative intent surgery
number of patients with ≤ 10% of residual viable tumor in lung and lymph nodes as evaluated by pathology review, divided by the number of all patients with posttreatment tumor tissue available
Time frame: 12 weeks
Pathological complete response (pCR)
Pathological complete response (pCR) is defined as the absence of any viable tumor cells in the entire surgical specimen (resected main lung tumor and resected lymph node tissue).
Time frame: 12 weeks
Radiological response by RECIST v1.1 criteria
The radiological response will be assessed according to RECIST v1.1
Time frame: 12 weeks
Event-free survival (EFS)
Event-free survival (EFS) is 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 according to RECIST v1.1; local or distant disease recurrence (including occurrence of new primary NSCLC); or death from any cause
Time frame: 78 months
Overall survival (OS)
Overall survival is defined as time from treatment initiation (administration of first neoadjuvant cycle) to the date of death from any cause. A subject who has not died at the end of the trial will be censored at last known date alive.
Time frame: 78 months
Rate of adverse events and serious adverse events rate
Safety assessments will include physical examinations including performance status (ECOG), clinical laboratory profile and adverse events. All observed toxicities and side effects will be graded according to NCI CTCAE v5.0 for all patients and their relationship to the study treatment will be assessed and summarized. The rate of adverse events and serious adverse events rate as well as the frequency of abnormal laboratory parameters will be determined.
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Time frame: 78 months