Atezolizumab + Pirfenidone for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: University of Kansas Medical Center
Must not be taking: Strong CYP1A2 inhibitors
Disqualifiers: Uncontrolled diabetes, Unstable angina, Active auto-immune diseases, others
No Placebo Group
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot use strong CYP1A2 inhibitors or systemic antibacterial or antifungal agents during the study.
What data supports the effectiveness of the drug combination Atezolizumab and Pirfenidone for Non-Small Cell Lung Cancer?
Research shows that Atezolizumab, when used with chemotherapy, can improve survival and response rates in patients with advanced non-small cell lung cancer. Atezolizumab is effective as a first-line treatment and has shown benefits in various studies, making it a promising option for this type of cancer.12345
Is the combination of Atezolizumab and Pirfenidone safe for humans?
Atezolizumab has been shown to be generally safe in humans, with common side effects including fatigue, decreased appetite, and nausea. Serious side effects can include pneumonia and liver issues, but these are less common. There is no specific safety data available for the combination with Pirfenidone in the provided research.678910
What makes the drug Atezolizumab unique for treating non-small cell lung cancer?
Atezolizumab is unique because it is an immune checkpoint inhibitor that targets PD-L1, helping the immune system attack cancer cells more effectively. It has shown significant benefits in prolonging survival in patients with advanced non-small cell lung cancer, especially those with high PD-L1 expression, and is used when the cancer has progressed after chemotherapy.1491112
Research Team
Chao H. Huang
Principal Investigator
The University of Kansas
Eligibility Criteria
Adults with stage 4 or recurrent non-small cell lung cancer (NSCLC) who've had certain prior treatments can join. They must be able to take oral meds, have good organ function and a life expectancy of at least 6 months. Smokers over one pack/day, those with recent serious illnesses, uncontrolled HIV, or active pneumonitis are excluded.Inclusion Criteria
I can take pills by mouth.
I am able to care for myself and perform daily activities.
I am 18 or older with confirmed non-small cell lung cancer.
See 11 more
Exclusion Criteria
I've had severe side effects from previous immunotherapy.
You smoke more than 20 cigarettes a day.
My HIV is not under control.
See 21 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Atezolizumab IV every 3 weeks and Pirfenidone orally with increasing doses until progression
Up to 2 years
Every 3 weeks (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 year
Treatment Details
Interventions
- Atezolizumab (Monoclonal Antibodies)
- Pirfenidone (Other)
Trial OverviewThe trial is testing if combining pirfenidone with atezolizumab improves treatment outcomes for NSCLC patients who've seen their cancer return after initial therapy. It aims to see if this combo can boost anti-tumor effects and overcome resistance to treatment.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: TreatmentExperimental Treatment1 Intervention
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
Atezolizumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
🇪🇺 Approved in European Union as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The University of Kansas Cancer Center, Westwood CampusKansas City, KS
The University of Kansas Cancer Center (KUCC)Fairway, KS
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Who Is Running the Clinical Trial?
University of Kansas Medical Center
Lead Sponsor
Trials
527
Patients Recruited
181,000+
parkview cancer institute
Collaborator
Trials
1
Patients Recruited
30+
References
Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. [2020]Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials. In these studies, atezolizumab significantly prolonged overall survival (OS) relative to docetaxel, regardless of PD-L1 status. Increasing PD-L1 expression was associated with OS improvements. Atezolizumab also demonstrated efficacy in the phase II FIR and BIRCH trials, as assessed by objective response rates (ORRs) in patients with tumours expressing PD-L1. Higher ORRs were seen in patients with high PD-L1 expression. Atezolizumab had an acceptable, manageable tolerability profile, with a low incidence of immune-related adverse events. Therefore, atezolizumab is a valuable treatment option for patients with advanced NSCLC that has progressed during or after chemotherapy.
Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis. [2022]Atezolizumab is becoming a significant therapy for non-small cell lung cancer (NSCLC), but its efficacy needs to be further improved. The aims of this study are to clarify the potency of atezolizumab-based therapy in advanced NSCLC patients with different clinical and molecular features, and to choose a better therapeutic regimen of atezolizumab to achieve more precise treatment in immunotherapy.
Squamous NSCLC Improves with Atezolizumab Plus Chemo. [2022]A combination of chemotherapy and the PD-L1 inhibitor atezolizumab may be an effective initial therapy for patients with advanced squamous non-small cell lung cancer. In a clinical trial, patients who received the combination had longer progression-free survival, a higher objective response rate, and a longer duration of response than patients who received chemotherapy alone, regardless of PD-L1 expression level.
Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. [2023]Purpose: Atezolizumab is a programmed death ligand 1 (PDL-1) blocking antibody that was approved for metastatic non-small cell lung cancer (NSCLC) in patients with disease progression. Various studies have been initiated to explore the effectiveness of atezolizumab among different patient cohorts and disease statuses, including as first-line therapy. The purpose of this paper is to identify and summarize the trials that use atezolizumab as a first-line agent in chemotherapy-naïve patients with NSCLC. Methods: A database search was performed on Pubmed, Embase, and Wiley Cochrane Library-Central Register of Controlled Trials to identify clinical trials using atezolizumab as first-line therapy in NSCLC. Additionally, ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) were searched to identify relevant clinical trials. Conference abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the American Association for Cancer Research were hand-searched. Any trial in which atezolizumab was used as first-line therapy in chemotherapy-naive patients with NSCLC was included. Results: Fifteen studies were ultimately included, all of which are current and ongoing. Of the 15 studies, 5 have reported results. When given in the first-line setting, atezolizumab had higher rates of objective response, progression-free survival, and overall survival, compared to the second and third-line settings. Among the 15 studies, atezolizumab is used as monotherapy (n = 5), in combination with chemotherapy (n = 6), in combination with targeted therapy such as bevacizumab (n = 1), as neoadjuvant/adjuvant therapy (n = 3), in combination with stereotactic body radiation therapy (n = 1), and in combination with or following chemoradiation (n = 1). Conclusion: Available evidence shows promising safety and efficacy with the use of atezolizumab as first-line therapy in NSCLC. Atezolizumab is currently being studied in a variety of treatment settings. If clinical benefits are shown, atezolizumab may deem to be a useful first-line agent in NSCLC.
Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. [2022]Before the availability of immunotherapy, chemotherapy was standard first-line therapy for non-small-cell lung cancer (NSCLC) lacking actionable gene alterations. Preclinical evidence suggests chemotherapy is immunomodulatory, supporting chemotherapy/immunotherapy combinations. Atezolizumab, anti-programmed death ligand-1 (PD-L1) antibody, blocks programmed cell death protein-1 and B7.1 interaction with PD-L1. GP28328 (NCT01633970) assessed atezolizumab with chemotherapy in multiple tumours; we report results for advanced, treatment-naïve NSCLC.
Safety and efficacy of atezolizumab in Chinese patients with previously treated locally advanced or metastatic non-small cell lung cancer: An open-label, single-arm, multicenter study. [2023]To evaluate the long-term safety and efficacy of atezolizumab monotherapy in Chinese patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC).
Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. [2022]In patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC), atezolizumab therapy improves survival with manageable safety. The open-label, single-arm phase III/IV TAIL study (NCT03285763) evaluated atezolizumab monotherapy in patients with previously treated NSCLC, including those with Eastern Cooperative Oncology Group performance status of 2, severe renal impairment, prior anti-programmed death 1 therapy, autoimmune disease, and age ≥75 years. Patients received atezolizumab intravenously (1200 mg) every 3 weeks. At data cut-off for final analysis, the median follow-up was 36.1 (range 0.0-42.3) months. Treatment-related (TR) serious adverse events (SAEs) and TR immune-related adverse events (irAEs) were the coprimary endpoints. Secondary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate, and duration of response. Safety and efficacy in key patient subgroups were also assessed. TR SAEs and TR irAEs occurred in 8.0% and 9.4% of patients, respectively. No new safety signals were documented. In the overall population, median OS and PFS (95% CI) were 11.2 months (8.9 to 12.7) and 2.7 months (2.3 to 2.8), respectively. TAIL showed that atezolizumab has a similar risk-benefit profile in clinically diverse patients with previously treated NSCLC, which may guide treatment decisions for patients generally excluded from pivotal clinical trials.
Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer.
Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]Since the US FDA-approval of the first immune checkpoint inhibitor, anticytotoxic T-lymphocyte antigen-4 monoclonal antibody ipilimumab, for metastatic melanoma on 28 March 2011, another six agents have been granted use among a multitude of tumors, including renal cell cancer, Hodgkin lymphoma, urothelial carcinoma and non-small-cell lung cancer. The first anti-programmed cell death ligand-1 monoclonal antibody to receive the FDA approval, atezolizumab (Tecentriq®), has yielded promising results among international Phase III trials in triple-negative breast cancer and small-cell lung cancer, expanding the field of cancer immunotherapies. Herein, we review the pharmacodynamic and pharmacokinetic properties of atezolizumab, its safety and efficacy data from early clinical trials and summarize data from Phase III IMpassion130 trial, prompting FDA and EMA approval of atezolizumab in metastatic triple-negative breast cancer. Finally, implications for clinical use and ongoing research will be briefly discussed.
U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months [95% confidence interval (CI), 11.8-15.7] in the atezolizumab arm compared with 9.6 months (95% CI, 8.6-11.2) in the docetaxel arm [hazard ratio (HR) = 0.74; 95% CI, 0.63-0.87; P = 0.0004]. Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI, 9.7-16.0) and 9.7 months (95% CI, 8.6-12.0; HR = 0.69; 95% CI, 0.52-0.92) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (≥20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (≥2%) grade 3 to 4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, aspartate aminotransferase increase, alanine aminotransferase increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of grade 3 to 4 pneumonitis, hepatitis, colitis, and thyroid disease. Clin Cancer Res; 23(16); 4534-9. ©2017 AACR.
Atezolizumab: First Global Approval. [2019]Atezolizumab (Tecentriq™)-a monoclonal antibody targeting programmed death ligand 1 (PD-L1 or CD274 antigen)-is being developed by Genentech as treatment for a variety of haematological malignancies and solid tumours. It been approved in the US as a second-line therapy for urothelial carcinoma and is awaiting approval as a second-line therapy for non-small cell lung cancer. This article summarizes the milestones in the development of atezolizumab leading to this first approval for urothelial carcinoma.
Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding-deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell-mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses. In subjects whose tumors progressed on first-line platinum-based chemotherapy, the objective response rate was 15%, the complete response rate was 5%, and 1-year overall survival was 36%. In subjects that were chemotherapy naïve and cisplatin ineligible, the objective response rate was 24%, the complete response rate was 7%, and 1-year overall survival was 57%. Better responses were associated with higher PD-L1 expression on the tumor-infiltrating leukocytes. These data suggest that patients with advanced bladder cancer treated with atezolizumab have significantly better response rates and survival than historical controls treated with other second-line regimens. The toxicity profile of atezolizumab is also favorable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first-line metastatic setting. Clin Cancer Res; 23(8); 1886-90. ©2016 AACR.