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

Official title

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

Overview

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.

Interventions

• Drug Atezolizumab
  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

Primary outcome measures

• Occurrence of Grade 3 toxicity [Time frame: Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days)]
• Occurrence of Grade 4 toxicity [Time frame: Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days)]

Secondary outcome measures (3)

• Overall response rate (ORR) of participants [Time frame: Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days)]
• Progression Free Survival (PFS) [Time frame: 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 [Time frame: Cycle 1 day 1 up to 1 year post-Cycle 1 day 1 (Each cycle is 21 days)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• The University of Kansas Cancer Center (KUCC) — Fairway
• The University of Kansas Cancer Center, Westwood Campus — Kansas City

Identifiers

NCT: NCT04467723 · IIT-2020-CAFs

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗