EZH2 Inhibitor, Tulmimetostat, and PD-1 Blockade for Treatment of Advanced Non-small Cell Lung Cancer

NCT05467748 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: SPLP-002-21F1673664
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 5

Brief Summary

This is an open label, single arm, phase Ib/II 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.

Conditions

Non Small Cell Lung Cancer

Keywords

PD-1 blockade; EZH2 inhibitor; Immunotherapy; Lung cancer

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  ORR assessed by RECIST v1.1

  2 years

• Safety and Tolerability

  Safety and tolerability assessed by CTCAE v5.0

  2 years

Secondary Outcomes (3)

• Disease control rate (DCR)

  2 years

• Progression Free Survival (PFS) and 1-year survival rate

  1 year

• Duration of Response (DOR)

  2 years

Study Arms (1)

combination of tulmimetostat and pembrolizumab

EXPERIMENTAL

Enrolled patients will receive combination treatment for whole study duration (2 years). For first cycle, patient will start tulmimetostat one week prior to start every 3 week pembrolizumab intravenous infusion (pembrolizumab will be given day 8 only for the first cycle, rest of cycles will be day 1 of each cycle).

Drug: Tulmimetostat

Interventions

Tulmimetostat DRUG

combination of oral tazemetostat and intravenous pembrolizumab treatment for patients with advanced non-small cell lung cancer

Also known as: Pembrolizumab

combination of tulmimetostat and pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent/assent for the trial. The trial consent includes future biomedical research.
• Male/female participants who are at least 18 years of age on the day of signing informed consent
• Patients with histologically confirmed diagnosis of advanced non-small cell lung cancer.
• Have a life expectancy of 12 weeks
• Participants who progressed from chemo(platinum-based)-immunotherapy, immunotherapy single agent or immuno-immuno combination therapies as front or second line of therapy.
• Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression (as defined in 4.c).
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• Progressive disease is determined according to RECISTv1.1.
• This determination is made by the investigator. Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.
• Have measurable disease per RECIST v1.1 as assessed by the investigator and site radiologist.
• Have provided archival tumor sample or newly obtained core or excisional biopsy of tumor lesion. Formalin fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides and the pretreatment biopsy is discretionary if suitable archival tissue sample is available.
• Adequate organ function. (must be within 10 days prior to start of study intervention)
• Absolute neutrophil counts (ANC) 1500/mm3

You may not qualify if:

• Primary diagnosis of low to intermediate grade of neuroendocrine lung cancer.
• Clinically active cerebral metastases. Patients with a prior diagnosis of cerebral metastases may be enrolled, provided that lesions have been adequately treated with radiation therapy or surgery, and have not required steroids for at least one month prior to study initiation.
• Is currently participating in or has participated in a study of an investigational agent within 4 weeks prior to study enrollment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Note: Participants must have recovered from all AEs due to previous therapies to Grade 1 or baseline. Participants with Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade 2 requiring treatment or hormone replacement may be eligible
• Prior exposure to tulmimetostat or other EZH2 inhibitors.
• EGFR or ALK altered patients.
• Immunotherapy naïve patients.
• Has a history of severe hypersensitivity reaction to pembrolizumab ( Grade 3).
• Has an active autoimmune disease that requires systemic treatment within the past 2 years or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic immunosuppressive agents, such as more than 10 mg of prednisone per day to control the disease. Patients with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Patient requiring intermittent use of bronchodilator or local steroid would not be excluded. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not excluded from the study.
• Patient is positive for Human Immunodeficiency Virus (HIV) (HIV 1 2 antibodies), active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA is detected); patients with negative Hepatitis C antibody testing may not need RNA testing.
• History of non-infectious pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has received a live virus vaccine or live-attenuated within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Subjects taking medications that are known as strong CYP3A4 inducers/inhibitors.

Sponsors & Collaborators

• VA Office of Research and Development: lead
• VA Greater Los Angeles Healthcare System: collaborator

Study Sites (5)

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, 90822, United States

NOT YET RECRUITING

VA Northern California Health Care System, Mather, CA

Sacramento, California, 95655-4200, United States

NOT YET RECRUITING

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161-0002, United States

RECRUITING

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105-2303, United States

RECRUITING

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030-4211, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Daniel S Shin, MD PhD

  Michael E. DeBakey VA Medical Center, Houston, TX

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel S Shin, MD PhD

CONTACT

(713) 578-4126; Daniel.Shin@va.gov

Quillan Huang, MD

CONTACT

(713) 791-1414; Quillan.Huang@va.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Phase IB: Determine RP2D of tulmimetostat by using BOIN design with 2 dose levels, 200 and 300 mg once daily in combination of standard pembrolizumab 200 mg IV every 3 weeks. Tulmimetostat is currently under evaluation as single agent for patients with various solid tumors. Phase II: Based on Simon Optimum two stage design, our total number of patients for phase II is 54 patients (patients treated with RP2D from phase IB will be included in the analysis). We will enroll 15 patients at first stage to determine futility of the trial and complete the remaining 39 patients during stage II.

Study Record Dates

• First Submitted: July 13, 2022
• First Posted: July 20, 2022
• Study Start: December 8, 2025
• Primary Completion (Estimated): December 8, 2027
• Study Completion (Estimated): December 7, 2029
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)