AzTrials
AzTrials

Non Small Cell Lung CancerPhase 1/2NCT05467748

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

A Phase 1/2 study testing Tulmimetostat in people with Non Small Cell Lung Cancer, run by VA Office of Research and Development at 5 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
Tulmimetostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
5 sitesUnited States
Study dates
8 Dec 2025to 7 Dec 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 31Show fewer
  • 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
  • Platelet count 100,000/mm3
  • Hemoglobin 9 g/dL without need for hematopoietic growth factor or transfusion support.
  • Serum creatinine 1.5 x ULN (Upper Limit of Normal), or 24-hour creatinine clearance 30 cc/min. (note: creatinine clearance need not be determined if the baseline serum creatinine is within normal limits)
  • Serum bilirubin 1.5 ×ULN OR direct bilirubin ULN for participants with total bilirubin levels >1.5 × ULN.
  • Aspartate amino transferase (AST) 2.5 ULN or 5XULN for subjects with liver metastases.
  • Alanine amino transferase (ALT) 2.5 ULN or 5XULN for subjects with liver metastases.
  • Alkaline phosphatase 2.5 X ULN of liver fraction if 2.5 X ULN
  • Serum albumin 2.5g/dL.
  • Prothrombin time (PT) 1.5 x ULN and INR 1.3
  • Partial thromboplastin time (PTT) 1.5 ULN.
  • ECOG 0-1.
  • Allowing patients who received over 30 Gy radiation therapy within 6 months of pembrolizumab treatment given the safety data from stage III patient received immunotherapy after concurrent chemotherapy and radiation.
  • Female subjects of childbearing/reproductive potential must have a negative serum pregnancy test within 72 hours prior to receiving the treatment of study medication.
  • Female subjects of childbearing potential and their partners must be willing to use a highly effective method of contraception as outlined in 5.5.2- Contraception, for the course of study through 183 days after the last dose of study medication.
  • Male subjects and their partners of childbearing potential must agree to use a highly effective method of contraception as outlined in 5.5.2- Contraception, starting with the first dose of study medication through 183 days after the last dose of therapy and refrain from donating sperm during this period.
  • Note: both for male and female subjects, abstinence is acceptable if this is life style or preferred method of contraception

Who cannot join

  • 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.
Show all 28Show fewer
  • 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.
  • (examples of inducers: not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort; examples of inhibitors: not limited to atazanavir, clarithromycin, indinavir, itraconazole, troleandomycin, voriconazole, and grapefruit or grapefruit juice. Please refer to this website for the full information: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ DrugInteractionsLabeling/ucm080499.htm; http://medicine.iupui.edu/clinpharm/ddis/)
  • Has not fully recovered from any effects of major surgery without significant detectable infection. Surgeries that required general anesthesia or major surgeries must be completed at least 4 weeks before first study intervention administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study intervention administration and participants should be recovered.
  • Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation ( 2 weeks of radiotherapy) to non-CNS disease.
  • Had administered concomitant medication(s) or food or beverage that are strong CYP3A inducers or inhibitors within 7 days prior to the first dose of study drug.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 year. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Inability to take oral medication or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of tulmimetostat.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Venous thromboembolism or pulmonary embolism within the last 3 months before starting study medication.
  • Subjects who undergone an allogenic tissue/solid organ transplantation.
  • A WOCBP who has a positive serum pregnancy test within 72 hours prior to study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Pregnant female subjects or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 183 days after the last dose of study treatment.
  • Patient is, at the time of signing consent, current use of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
  • Has known psychiatric disorders that would interfere with cooperation with the requirement of the study.

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Daniel S Shin, MD PhD contact

(713) 578-4126 ext. 224126

Daniel.Shin@va.gov

Quillan Huang, MD contact

(713) 791-1414

Quillan.Huang@va.gov

5 sites in 1 country

United States5 sites, 5 recruiting

  • VA Ann Arbor Healthcare System, Ann Arbor, MI

    Ann Arbor, Michigan, 48105-2303

    Garth Strohbehn, MD, Garth.Strohbehn@va.gov

    Recruiting

  • Michael E. DeBakey VA Medical Center, Houston, TX

    Houston, Texas, 77030-4211

    Zhifang Zhao, PhD, 713-791-1414 ext. 220038, Zhifang.Zhao@va.gov

    Michelle V Espiritu-Washburn, MBBS, (713) 794-7939, Michelle.Espiritu@va.gov

    Recruiting

  • VA Long Beach Healthcare System, Long Beach, CA

    Long Beach, California, 90822

    Pankaj Gupta, MD, Pankaj.Gupta@va.gov

    Not yet recruiting

  • VA Northern California Health Care System, Mather, CA

    Sacramento, California, 95655-4200

    Tianhong Li, MD, Tianhong.li@va.gov

    Not yet recruiting

  • VA San Diego Healthcare System, San Diego, CA

    San Diego, California, 92161-0002

    Paul Cheng, MD, Paul.Cheng1@va.gov

    Recruiting

Other trials in United States

About this study

Official title: Phase Ib/II Study of Safety and Efficacy of EZH2 Inhibitor, Tulmimetostat, and PD-1 Blockade for Treatment of Advanced Non-small Cell Lung Cancer

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.

Read the 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 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 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.

Being tested
Tulmimetostat
Keywords
PD-1 blockade, EZH2 inhibitor, Immunotherapy, Lung cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TulmimetostatDrug

    Also called Pembrolizumab

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

Study groups in NCT05467748
Study groupRoleWhat they receive
combination of tulmimetostat and pembrolizumabExperimentalEnrolled 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).
Receives: Drug: Tulmimetostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    ORR assessed by RECIST v1.1

    Measured: 2 years

  2. Safety and Tolerability

    Safety and tolerability assessed by CTCAE v5.0

    Measured: 2 years

Secondary outcomes (3)

  1. Disease control rate (DCR)

    DCR (complete response, partial response and stable disease) assessed by RECIST v1.1

    Measured: 2 years

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

    PFS assessed by Kaplan Meyer survival analysis.

    Measured: 1 year

  3. Duration of Response (DOR)

    DOR assessed by RECIST v1.1

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2022
  2. Study start8 Dec 2025
  3. Primary completion8 Dec 2027 (estimated)
  4. Study completion7 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
66 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05467748
Sponsor's protocol ID
SPLP-002-21F
Other IDs
1673664
Status last verified
Jan 2026
First submitted
13 Jul 2022
Last updated
27 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tulmimetostat in people with Non Small Cell Lung Cancer, run by VA Office of Research and Development at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Daniel S Shin, MD PhD ((713) 578-4126 ext. 224126, Daniel.Shin@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05467748.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in