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

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

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.

Study Overview

• Status: Recruiting
• Conditions: NSCLC Stage IV; NSCLC, Recurrent
• Intervention / Treatment: Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: KUCC Navigator; Phone Number: 9135883671; Email: KUCC_Navigation@kumc.edu

Study Locations

• United States
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Not yet recruiting
      • The University of Kansas Cancer Center (KUCC)
      • Contact: KUCC Navigator; Phone Number: 913-588-3671; Email: kucc_navigation@kumc.edu
    • Kansas City, Kansas, United States, 66205
      • Recruiting
      • The University of Kansas Cancer Center, Westwood Campus
      • Contact: KUCC Navigation; Phone Number: 913-588-3671; Email: kucc_navigation@kumc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; 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; 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; Other Names: Pirfenidone

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: parkview cancer institute
• Investigators: Principal Investigator: Chao Huang, MD, The University of Kansas

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2022
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: July 8, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (Actual): July 13, 2020

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pirfenidone; Atezolizumab
• Other Study ID Numbers: IIT-2020-CAFs

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No