Combination of Atezolizumab and Pirfenidone in Second-line and Beyond NSCLC

Study Overview
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Brief Summary
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The purpose of this study is to see if adding pirfenidone to atezolizumab will increase anti tumor activity and reduce treatment resistance in stage 4 and recurrent non- small cell lung cancer participants.

Official Title
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CAFs (Combination of Atezolizumab and Pirfenidone in Second-line and Beyond NSCLC): a Phase I/II Study

Conditions
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NSCLC Stage IV, NSCLC, Recurrent

Intervention / Treatment
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* Drug: Atezolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant or legal representative is able to provide written informed prior to performing any protocol-related procedures Is willing and able to comply with scheduled visits, treatment schedule, laboratory testing and other requirements of the study Men or women at least 18 years of age with histologically or cytologically confirmed non-small cell lung cancer Previous history of other than lung cancer is allowed if no active treatment for that cancer within 1 year Life expectancy of at least 6 months De novo stage IV or recurrent NSCLC without actionable mutation (e.g. EGFR/ ALK/ ROS-1) that was previously treated with either PD-1 / PD-L1 or the combination of PD1/PDL1 and cytotoxic chemotherapy, no more than 2 systemic regimens for metastatic disease with measurable disease *. Maintenance therapy will be considered part of the 1 regimen At least 1 measurable lesion PDL1 TPS score less than 1% or unknown: first-line must be PD1/PDL1 inhibitor in combination with chemotherapy Early stage (I-III) NSCLC treated with adjuvant or neoadjuvant chemotherapy then PD1/PDL1 inhibitor treatment for recurrent disease Recurrent Unresectable stage III NSCLC treated with prior chemoradiation followed by maintenance PD1/PDL1 inhibitor with measurable disease Eastern Cooperative Group (ECOG) Performance Status 0 - 2 Is able to swallow oral medications Adequate hematologic function Adequate organ function Exclusion Criteria: The presence of any other concurrent severe and/or uncontrolled medical condition that would, in the investigator or treating physician's judgement, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol Has received investigational agents within 14 days or 5 half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment Has a known hypersensitivity to atezolizumab or pirfenidone Has active medical or psychiatric illness that would interfere with the study treatment Has uncontrolled diabetes Has any of the following cardiac diagnoses: Unstable angina Myocardial infarction within 6 months Uncontrolled congestive heart failure Left ventricular ejection fraction < 35% Has a history of any Grade 3 or 4 toxicities to a prior checkpoint inhibitor treatment Is pregnant or breast feeding Uncontrolled HIV Clinically diagnosed with grade 2 or 3 radiation-induced lung injury within the last 3 months prior to registering for the study Has a history of idiopathic pneumonitis that required systemic agent including steroid Has drug-induced pneumonitis Has evidence of active pneumonitis on screening chest computed tomography (CT) scan Smoker of more than 1 pack / day Has active peptic ulcer diagnosed within 4 weeks of enrollment Active infection requiring systemic treatment Current use of systemic antibacterial or antifungal agent Prior monoclonal antibody within 4 weeks before study Day 1 Exception: The use of denosumab Patient not recovered to ≤ Grade 1 from AEs due to agents administered more than 4 weeks earlier Concurrent use of other investigational agents Uncontrolled or symptomatic brain metastasis or leptomeningeal disease that requires use of steroids Use of strong CYP1A2 inhibitors Previous history of cancer with active treatment within less than 1 year of enrollment Active auto-immune diseases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Atezolizumab (Tecentriq) intravenous (IV) 1200mg flat dose day 1 then every 3 weeks. Pirfenidone (Esbriet) orally (PO) with food according to this schedule: Days 1-14: 267 milligrams (mg) orally three times per day (PO TID) Days 15-29: 534 mg PO TID Days 30 onward until progression: 801 mg PO TID | Drug: Atezolizumab<br>* Atezolizumab is given as an intravenous infusion at 1200 mg every 3 weeks. Pirfenidone is taken by mouth 3 times a day with the dose increasing every 2 week until day 30<br>* Other names: Pirfenidone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Grade 3 toxicity | CTCAE v5.0 | Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days) | 
| Occurrence of Grade 4 toxicity | CTCAE v5.0 | Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) of participants | RECIST 1.1 | Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days) | 
| Progression Free Survival (PFS) | RECIST 1.1 | From Cycle 1 day 1 (Each cycle is 21 days) for up to 2 years after end of treatment | 
| 1-year overall survival (OS) rate: Proportion of participants alive at 1 year from Cycle 1 day 1 | Medical records | Cycle 1 day 1 up to 1 year post-Cycle 1 day 1 (Each cycle is 21 days) |