A Study of Valemetostat in Combination With Atezolizumab in People With Lung Cancer

Inclusion Criteria:

• Signed informed consent form (ICF)

• Ability to comply with the study protocol as per the investigator's judgment

• Age ≥ 18 years at the time of signing the ICF

• Life expectancy ≥ 12 weeks

• ECOG performance status 0 or 1

• Pathologically confirmed diagnosis of newly diagnosed extensive-stage small celllung cancer. Patients with a diagnosis of combined small cell lung cancer with otherhistologies may be considered for inclusion if the predominant histology is SCLC andonly after discussion with the study PI.

• Radiographically documented RECIST version 1.1 stable disease, partial or completeresponse after initial treatment with a platinum doublet regimen in combination withatezolizumab for 4 cycles. It is acceptable to have no measurable disease at thestart of this study.

• Must be able to begin therapy within 4 weeks of completing the fourth cycle ofchemotherapy and immunotherapy.

• Adequate hematologic and end-organ function, as defined by the following laboratorytest results obtained within 14 days prior to initiation of study treatment.Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 2 weeks prior to screening laboratorytests: o Adequate bone marrow function as defined by:

• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500/µL)

• Hemoglobin ≥ 9 g/dL

• Platelets ≥ 100 x 10^9/L o Adequate renal function as defined by:

• Creatinine clearance ≥ 30 mL/min as calculated using the Cockcroft-Gault equation o Adequate hepatic function as defined by:

• AST, ALT, and alkaline phosphatase (ALP) ≤ 3 x ULN with the following exception:

• Patients with documented liver metastases: AST, ALT and ALP ≤ 5 x ULN

Exclusion Criteria:

• Any active uncontrolled systemic diseases or other medical conditions considered tobe poorly controlled by the investigator including but not limited to bleedingdiatheses, that could in the investigator's opinion, potentially interfere withcompletion of study procedures or interpretation of study outcomes.

• Patients who receive consolidative chest radiation after completion of initialchemotherapy and immunotherapy.

• Symptomatic CNS metastases

• Patients with treated CNS metastases are allowed on the study if their clinicalsymptoms are adequately controlled and the daily dose of steroid use is equivalentto or less than 10 mg of prednisone.

• Receiving concomitant treatment with a moderate or strong inducer of CYP3A within 14days of first receipt of valemetostat o Consumption of herbs/fruits that may have aninfluence on PK of valemetostat (strong CYP3A inhibitors or inducers) such as St.John's wort, star fruit, Seville orange or Seville orange-containing foods andbeverages, grapefruit or grapefruit-containing food or beverages should be avoidedfrom 14 days prior to the start of the study and throughout the entire study.

Prior exposure to valemetostat or other inhibitors of enhancer of zeste homologue-2 (EZH2)

• Refractory nausea and vomiting, malabsorption, biliary shunt, significant bowelresection, or any other condition that significantly affects gut motility orabsorption and would preclude adequate absorption of valemetostat in the opinion ofthe treating physician and/or PI.

• Currently receiving radiation therapy, or who have received radiation within 2 weeksprior to the initiation of study treatment, or who plan to receive radiation therapywithin the safety evaluation period for dose-limiting toxicity during Cycle 1.

• Unresolved toxicities from previous anticancer therapy, defined as toxicities (otherthan alopecia) not yet resolved to NCI-CTCAE version 5.0, Grade ≤ 1 or baseline. o NOTE: Participants may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to Grade >2 for at least 3 months prior to enrollment andmanaged with standard of care treatment) that the investigator deems related toprevious anticancer therapy, comprised of the following:

• Chemotherapy-induced neuropathy

• Residual toxicities from prior IO treatment: Grade 1 or Grade 2 endocrinopathieswhich may include:

• Hypothyroidism/ hyperthyroidism

• Type I diabetes

• Hyperglycemia

• Adrenal insufficiency

• Adrenalitis

• Skin hypopigmentation (vitiligo)

• Patients who have had a major surgery or significant traumatic injury within 4 weeksof start of study drug, patients who have not recovered from the side effects of anymajor surgery (defined as requiring general anesthesia). o NOTE: Procedures such as a percutaneous biopsy, pleural catheter insertion,placement of a central venous catheter or other minor procedures are permitted.

• Uncontrolled or significant cardiovascular disease, including the following:

• Evidence of prolongation of QT/QTc interval (e.g., repeated episodes of QT correctedfor heart rate using Fridericia's method [QTcF] >470 ms). Electrocardiogram must beregistered at rest. For any ECG assessment, if the initial ECG shows a prolongedQTc, then two additional ECGs will be obtained, resulting in three specimens takenafter a space of 1 minute, and the mean of the 3 ECGs will be used to determineeligibility and for grading of TRAEs.

• Myocardial infarction within 6 months prior to screening o Uncontrolled anginapectoris within 6 months prior to screening o New York Heart Association (NYHA)Class 3 or 4 congestive heart failure

• Uncontrolled hypertension (resting systolic blood pressure >160 mmHg or diastolicblood pressure >100 mmHg)

• Have a known hypersensitivity to any of the components of or known hypersensitivityto either the study drug itself or any of the inactive ingredients in the study drugproduct.

• Known liver cirrhosis.

• Uncontrolled active infection requiring IV antibiotic, antiviral, or anti-fungalmedications within 14 days prior to initiation of study treatment. o Infections controlled on concurrent anti-microbial agents and anti-microbialprophylaxis per institutional guidelines are acceptable.

• Congenital or acquired immunodeficiency, including patients with known history orinfection with human immunodeficiency virus (HIV). o NOTE: HIV-positive patients who are taking anti-retroviral therapy are stillineligible due to potential PK interactions with valemetostat.

• Active tuberculosis

• Active hepatitis B virus (HBV) infection (chronic or acute), defined as having apositive hepatitis B surface antigen (HBsAg) test followed by a positive HBV RNAtest within 28 days prior to the first dose of study drug. Hepatitis B testing (HBVsurface antigen and core antibody) is required only if not done previously. o Patients with a past or resolved HBV infection, defined as having a negative HBsAgtest and a positive total hepatitis B core antibody (HBcAb) test at screening, areeligible for the study.

• Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibodytest followed by a positive HCV RNA test within 28 days prior to the first dose ofstudy drug. Hepatitis C testing (HCV antibody) is required only if not donepreviously. o The HCV RNA test will be performed only for patients who have a positive HCVantibody test.

• Prior malignancy, active within the previous 3 years, except for locally curablecancer that is currently considered as cured or successfully resected, such as basalor squamous cell carcinoma, superficial bladder cancer, gastric cancer or carcinomain situ of the prostate, cervix, or breast.

• Female patients who have a positive serum pregnancy test during screening or apositive urine pregnancy test on Day 1 before first dose of study drug.

• Female patients who are lactating and/or plan to breastfeed during the studytreatment or at any point leading up to and including 6 months after the last studydrug dose.