Combining Atezolizumab and Pirfenidone for Advanced Lung Cancer

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

This study is testing if adding pirfenidone to atezolizumab can help people with advanced lung cancer who have already been treated feel better and fight their cancer more effectively.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Kansas Medical Center (Academic / other)
• Drugs / interventions: atezolizumab, denosumab, chemotherapy, radiation
• Locations: 2 sites (Fairway, Kansas and 1 other locations)
• Trial ID: NCT04467723 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of adding pirfenidone to atezolizumab in patients with stage IV and recurrent non-small cell lung cancer (NSCLC). The goal is to enhance anti-tumor activity and reduce treatment resistance in participants who have previously undergone treatment. Eligible patients must have measurable disease and a specific PD-L1 expression status. The study is designed to evaluate the safety and efficacy of this combination therapy in a clinical setting.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with stage IV or recurrent NSCLC who have previously been treated with PD-1/PD-L1 inhibitors.

Not a fit: Patients with actionable mutations such as EGFR, ALK, or ROS-1 may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option that improves outcomes for patients with advanced lung cancer.

How similar studies have performed: While the combination of atezolizumab and pirfenidone is a novel approach, similar studies exploring combination therapies in lung cancer have shown promising results.

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

Where this trial is running

Fairway, Kansas and 1 other locations

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

Study contacts

• Principal investigator: Chao Huang, MD — The University of Kansas
• Study coordinator: KUCC Navigator

Conditions NSCLC Stage IV; NSCLC, Recurrent