Tulmimetostat and Pembrolizumab for Advanced Non-Small Cell Lung Cancer
This study is testing a new combination treatment for advanced non-small cell lung cancer (NSCLC) that has worsened after previous treatments. The treatment involves two drugs: tulmimetostat, which is taken by mouth, and pembrolizumab, which is given through a vein. Researchers want to see how safe and effective this combination is. They are particularly interested in whether the tumors shrink or disappear (Objective Response Rate). You may be able to join if you are at least 18 years old and have advanced NSCLC. The study is currently recruiting about 66 participants.
- Study design
- This is an open-label, single-arm, Phase Ib/II study, meaning all participants receive the same treatment, and everyone knows what treatment is being given. It plans to enroll 66 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will measure Objective Response Rate, safety, and tolerability for up to 2 years.
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NCT05467748
EZH2 Inhibitor, Tulmimetostat, and PD-1 Blockade for Treatment of Advanced Non-small Cell Lung Cancer
Recruiting
PHASE1Ages 18+InterventionalTreatmentVA Office of Research and DevelopmentGovernment-funded
~66 participants
Updated 2026-01-27 on ClinicalTrials.gov
What's tested:Tulmimetostat
At a glance
Recruiting sites
3 of 5 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Objective Response Rate (ORR)
Measured over 2 years
+1 more outcome measured
Conditions
Where it's being run
5 sites across 3 statesCalifornia3
Michigan1
Texas1
Study leadership
- Daniel S Shin, MD PhD · PRINCIPAL_INVESTIGATOR · Michael E. DeBakey VA Medical Center, Houston, TX
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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:
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.
Exclusion
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.
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.
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.
What this trial measures
- Objective Response Rate (ORR)2 years
ORR assessed by RECIST v1.1
- Safety and Tolerability2 years
Safety and tolerability assessed by CTCAE v5.0