Viewing Study NCT05467748



Ignite Creation Date: 2024-05-06 @ 5:52 PM
Last Modification Date: 2024-10-26 @ 2:37 PM
Study NCT ID: NCT05467748
Status: NOT_YET_RECRUITING
Last Update Posted: 2024-04-05
First Post: 2022-07-13

Brief Title: EZH2 Inhibitor Tulmimetostat and PD-1 Blockade for Treatment of Advanced Non-small Cell Lung Cancer
Sponsor: VA Office of Research and Development
Organization: VA Office of Research and Development

Study Overview

Official Title: Phase IbII Study of Safety and Efficacy of EZH2 Inhibitor Tulmimetostat and PD-1 Blockade for Treatment of Advanced Non-small Cell Lung Cancer
Status: NOT_YET_RECRUITING
Status Verified Date: 2024-10
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: This is an open label single arm phase IbII clinical trial of checkpoint blockade pembrolizumab and EZH2 inhibitor tulmimetostat 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
Detailed 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 tulmimetostat can re-sensitive cancer cells to respond to PD-1 blockade pembrolizumab and designed phase IbII 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 safetytolerability and Objective Response Rate ORR Complete Response and Partial Response evaluated by RECIST v11 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 BOIN Bayesian Optimal Interval Design with 2 dose levels 200 and 300 mg for tulmimetostat starting 200mg mg orally once daily Tulmimetostat 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 planned to enroll 18 patients during phase Ib to determine 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 Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: True
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: False
Is an FDA AA801 Violation?: None
Secondary IDs
Secondary ID Type Domain Link
1673664 OTHER VA Greater Los Angeles Healthcare System None