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

University of Kansas

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: NSCLC, Recurrent; NSCLC Stage IV

Treatments: Drug: Atezolizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT04467723

IIT-2020-CAFs

Details and patient eligibility

About

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.

Enrollment: 25 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Treatment

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab