Clinical Trials Logo

Clinical Trial Summary

This is an open label, single arm, phase Ib/II clinical trial of checkpoint blockade, pembrolizumab and EZH2 inhibitor, tazemetostat combination therapy for patients with advanced non-small cell lung cancer who have progressed from front or second-line treatment. Patients will be enrolled at multiple Veterans Affairs Medical Centers.


Clinical Trial Description

It is pleasing to witness the fulfillment of the promise of cancer immunotherapy becoming a reality for patients with many types of advanced cancer. However, even with this remarkable progress, majority of patients are not responding and substantial number of patients are progressing after initial response to checkpoint blockade immunotherapy. The field is undertaking major task to identify suitable combinatorial approach to improve the efficacy of checkpoint blockade immunotherapy and biomarker for better patient selection. Evidence suggests that EZH2 (Enhancer Zeste Homolog: enzymatic component of Polycomb Repressive Complex 2) plays a significant role in prognosis of patients with non-small cell lung cancer and animal studies showed that EZH2 targeting can improve the efficacy of immunotherapy. Based on this, it was hypothesized that EZH2 inhibitor, tazemetostat can re-sensitive cancer cells to respond to PD-1 blockade, pembrolizumab and designed phase Ib/II single arm, open label study to test this hypothesis for patients with advanced non-small cell lung cancer who progressed from front or second line of therapy (expecting majority of patients experienced checkpoint blockade immunotherapy). The primary objectives of this study are safety/tolerability and Objective Response Rate (ORR: Complete Response and Partial Response) evaluated by RECIST v1.1. Key secondary objectives are disease control rate, progression free survival at 1 year, and duration of response. The study will employ safety lead-in phase Ib using 3+3 standard dose escalation scheme with 3 dose levels for tazemetostat, starting 400, up to 600 and 800 mg orally twice daily. Tazemtostat will be administered for 7 days prior to pembrolizumab 200 mg intravenous every 3 weeks that is defined as run-in phase (only prior to first cycle). It is estimated that 6 to 18 patients will be enrolled to determined recommended dose for phase II (RP2D). The sample size for phase II was calculated using Simon optimum two-stage design in order to determine the futility at early time. In the first stage, 15 subjects will be enrolled. If 2 or more responses are observed, an additional 39 subjects will be accrued during second phase. If in total there are 8 or more responses, we will consider the drug combination worthy of further clinical development, provided other factors such as toxicity and progression-free survival also appear favorable. For this phase II portion, up to 54 subjects are enrolled. This design has a one-sided alpha of 5% and a power of 80%. Planned duration of enrollment is 2 years, correlative studies (methyl marker: H3K27me3 and PD-L1, exome, RNA, circulating ctDNA sequencing and immune monitoring) are proposed using tumor biopsies (on treatment biopsy is optional) and blood samples before and after the treatment. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05467748
Study type Interventional
Source VA Office of Research and Development
Contact Daniel S Shin, MD PhD
Phone (310) 478-3711
Email Daniel.Shin@va.gov
Status Not yet recruiting
Phase Phase 1/Phase 2
Start date July 1, 2024
Completion date June 30, 2028

See also
  Status Clinical Trial Phase
Recruiting NCT05094804 - A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents Phase 1/Phase 2
Recruiting NCT05707286 - Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
Recruiting NCT04258137 - Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study N/A
Completed NCT01945021 - Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC Phase 2
Completed NCT04487457 - Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy
Terminated NCT04022876 - A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Side Effects (Chemoprotection) Phase 1
Recruiting NCT05898763 - TEIPP Immunotherapy in Patients With NSCLC Phase 1/Phase 2
Recruiting NCT05532696 - Phase 1b/2 Study to Evaluate ABT-101 in Solid Tumor and NSCLC Patients Phase 1/Phase 2
Completed NCT04311034 - A Study of RC48-ADC in Subjects With Advanced Non-small Cell Lung Cancer Phase 1/Phase 2
Active, not recruiting NCT03177291 - Pirfenidone Combined With Standard First-Line Chemotherapy in Advanced-Stage Lung NSCLC Phase 1
Terminated NCT03257722 - Pembrolizumab + Idelalisib for Lung Cancer Study Phase 1/Phase 2
Completed NCT00349089 - Trial on Refinement of Early Stage Lung Cancer Adjuvant Therapy Phase 2
Completed NCT05116891 - A Phase 1/2 Study of CAN04 in Combination With Different Chemotherapy Regimens in Subjects With Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT04571632 - Clinical Trial of SBRT and Systemic Pembrolizumab With or Without Avelumab/Ipilimumab+ Dendritic Cells in Solid Tumors Phase 2
Terminated NCT03599518 - DS-1205c With Gefitinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer Phase 1
Not yet recruiting NCT06020989 - Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy Phase 2
Withdrawn NCT03982134 - PDR001 + Panobinostat for Melanoma and NSCLC Phase 1
Withdrawn NCT03574649 - QUILT-2.024: Phase 2 Neoadjuvant, Consolidation, and Adjuvant Combination NANT Immunotherapy Versus Standard of Care in Subjects With Resectable Non-small Cell Lung Cancer Phase 2
Withdrawn NCT02844140 - DE-CT in Lung Cancer Proton Therapy N/A
Terminated NCT02628535 - Safety Study of MGD009 in B7-H3-expressing Tumors Phase 1