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

Exclusion Criteria

• •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.
• •(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.