A Study of Valemetostat Tosylate Plus Pembrolizumab Versus Pembrolizumab Alone in First-Line NSCLC Without Actionable Genomic Alterations

Exclusion Criteria18

• Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting:
• Any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, or CD137).
• Has previously been treated with any enhancer of zeste homolog inhibitors.
• Participants who received adjuvant or neoadjuvant therapy other than those listed in the exclusion criterion above are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the current diagnosis of advanced or metastatic disease.
• Has received a live vaccine or live attenuated vaccine within 30 days prior to the first dose of trial intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccines. Note: Administration of killed vaccines is allowed.
• Has an active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of systemic disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Inhaled, intranasal, intraocular, intra-articular, or topical steroids and adrenal replacement steroids are permitted in the absence of active autoimmune disease.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (at doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial intervention. Note: Short-course systemic corticosteroids (eg, prevention of/treatment for transfusion reaction) or steroid use for a noncancer indication (eg, adrenal replacement) is permissible.
• Has a known active or untreated CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate, provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks by repeat imaging (note: repeat imaging should be performed during trial screening), clinically stable, and without requirement of steroid treatment for at least 14 days before the first dose of trial intervention. Note: A CT scan or MRI scan of the brain at Baseline is required for all participants. For participants in whom CNS metastases are first discovered at Screening, the treating investigator should delay trial intervention to complete any necessary treatment followed by a proper washout period and document the stability of CNS metastases with repeat imaging at least 4 weeks later (in which case repetition of all screening activities may be required).
• Has uncontrolled or significant cardiovascular disease, including the following:
• Mean QT interval corrected for heart rate using Fridericia's formula \>470 ms (based on the average of screening triplicate 12-lead ECG determinations)
• Myocardial infarction within 6 months prior to Screening
• Uncontrolled angina pectoris within 6 months prior to Screening
• New York Heart Association Class 3 or 4 congestive heart failure
• Uncontrolled hypertension (resting systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg)
• Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
• Has a history of radiation pneumonitis.
• Has had an allogenic tissue/solid organ transplant.