Sample 54

Inclusion Criteria:Has histologically or cytologically confirmed triple negative breast carcinoma that is either metastatic (stage IV of the TNM classification) or locally recurrent and not amenable to local curative treatment.Evidence of measurable, locally recurrent or metastatic disease based on imaging studies within 28 days before the first dose of study drug.Has received at least 1, but no more than 2, prior lines of systemic therapy for locally recurrent and/or metastatic disease.If participant has a history of treated asymptomatic CNS metastases they are eligible, provided they meet all of the following criteria: participant has measurable disease outside CNS; participant does not have metastases to midbrain, pons, medulla or spinal cord; participant is not on corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are allowed); participant has not had whole-brain radiation within 6 weeks prior to study enrollment; participant has stable CNS disease as demonstrated by at least 4 weeks of stability between the last intervention scan and the study screening scan.ECOG performance status of 0 or 1.Has acceptable, applicable laboratory parameters.Female participants must not be pregnant; willing to use 2 methods of birth control/abstinence if applicable through 120 days after the last dose of study drug.Experienced resolution of toxic effect(s) of the most recent prior anti-cancer therapy to Grade <1 (except alopecia or neuropathy).Able to understand and give written informed consent and comply with study procedures.Exclusion Criteria:Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.Active autoimmune disease including active diverticulitis, symptomatic peptic ulcer disease, colitis, or inflammatory bowel disease that has required systemic treatment in past 2 years.Previously treated with a PD-1/PD-L1-blocking antibody or a histone deacetylase inhibitor.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, including, but not limited to: history of immune deficiencies or autoimmune disease; myocardial infarction or arterial thromboembolic events within 6 months prior to screening or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc interval > 470 msec; uncontrolled hypertension or diabetes mellitus; another known malignancy that is progressing or requires active treatment; active infection requiring systemic therapy; known active central nervous system (CNS) metastases and/or carcinomatous meningitis.Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption.Received a live vaccine within 30 days of the first dose of treatment.Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to enrollment or who has not recovered from AEs due to mAb agents administered more than 4 weeks earlier.Prior chemotherapy within 3 weeks, targeted small molecule therapy or radiation therapy within 2 weeks prior to enrollment, or who has not recovered (i.e., ≤Grade 1 at enrollment) from AEs due to a previously administered agent.Received transfusion of blood products or administration of colony stimulating factors within 4 weeks prior to the first dose of treatment.Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.Currently receiving treatment with any other agent listed on the prohibited medication list.If female, is pregnant, breastfeeding, or expecting to conceive starting with the screening visit through 120 days after the last dose of study drug.Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).Known active hepatitis B or hepatitis C.Allergy to benzamide or inactive components of entinostat.History of allergies to any active or inactive ingredients of atezolizumab.Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

18 Page 36 of 141 Figure 5-5 CONFIDENTIAL SYNDAX PHARMACEUTICALS In the J1353 trial, 11 patients with advanced NSCLC were treated with either entinostat plus azacitidine or placebo plus azacitidine. The response rate was 100% in the entinostat plus azacitidine group, with 100% of the patients achieving PD or SD. This response rate was higher than that observed in the prior J1353 trial, which had a 15% response rate. The data suggest that the combination of entinostat and azacitidine may be a promising new agent for the treatment of advanced NSCLC. Product: Entinostat Protocol Number: SNDX-275-0602 (TRIO025) Date: 11 Sep 2018 Page 37 of 141 Figure 5-6 CONFIDENTIAL SYNDAX PHARMACEUTICALS The combination of entinostat and azacitidine has shown promise in the treatment of advanced NSCLC, with a 100% response rate in the J1353 trial. This suggests that the combination of these two agents may be a highly effective treatment for NSCLC. However, the use of entinostat in combination with other immune checkpoint inhibitors, such as PD-1 or PDL-1, has not yet been studied in a large-scale Phase 3 trial. The Phase 3 trial is currently in the planning stages, with the goal of assessing the safety and efficacy of entinostat in combination with a PD-1 or PDL-1 inhibitor in a large patient population. Product: Entinostat Protocol Number: SNDX-275-0602 (TRIO025) Date: 11 Sep 2018 Page 38 of 141 Figure 5-6 (Wrangle 2013) Clinical. The combination of entinostat and azacitidine has shown promise in the treatment of advanced NSCLC, with a 100% response rate in the J1353 trial. This suggests that the combination of these two agents may be a highly effective treatment for NSCLC. However, the use of entinostat in combination with other immune checkpoint inhibitors, such as PD-1 or PDL-1, has not yet been studied in a large-scale Phase 3 trial. The Phase 3 trial is currently in the planning stages, with the goal of assessing the safety and efficacy of entinostat in combination with a PD-1 or PDL-1 inhibitor in a large patient population. Product: Entinostat Protocol Number: SNDX-275-0602 (TRIO025) Date: 11 Sep 2018 Page 39 of 141 Figure 5-7 CONFIDENTIAL SYNDAX PHARMACEUTICALS The combination of entinostat and azacitidine has shown promise in the treatment of advanced NSCLC, with a 100% response rate in the J1353 trial. This suggests that the combination of these two agents may be a highly effective treatment for NSCLC. However, the use of entinostat in combination with other immune checkpoint inhibitors, such as PD-1 or PDL-1, has not yet been studied in a large-scale Phase 3 trial. The Phase 3 trial is currently in the planning stages, with the goal of assessing the safety and efficacy of entinostat in combination with a PD-1 or PDL-1 inhibitor in a large patient population. Product: Entinostat Protocol Number: SNDX-275-0602 (TRIO025) Date: 11 Sep 2018 Page 40 of 141 Figure 5-7 (Wrangle 2013) Clinical. The combination of entinostat and azacitidine has shown promise in the treatment of advanced NSCLC, with a 100% response rate in the J1353 trial. This suggests that the combination of these two agents may be a highly effective treatment for NSCLC. However, the use of entinostat in combination with other immune checkpoint inhibitors, such as PD-1 or PDL-1, has not yet been studied in a large-scale Phase 3 trial. The Phase 3 trial is currently in the planning stages, with the goal of assessing the safety and efficacy of entinostat in combination with a PD-1 or PDL-1 inhibitor in a large patient population. Product: Entinostat Protocol Number: SNDX-275-0602 (TRIO025) Date: 11 Sep 2018 Page 41 of 141 Figure 5-8 CONFIDENTIAL SYNDAX PHARMACEUTICALS The combination of entinostat and azacitidine has shown promise in the treatment of advanced NSCLC, with a 100% response rate in the J1353 trial. This suggests that the combination of these two agents may be a highly effective treatment for NSCLC. However, the use of entinostat in combination with other immune checkpoint inhibitors, such as PD-1 or PDL-1, has not yet been studied in a large-scale Phase 3 trial. The Phase 3 trial is currently in the planning stages, with the goal of assessing the safety and efficacy of entinostat in combination with a PD-1 or PDL-1 inhibitor in a large patient population. Product: Entinostat Protocol Number: SNDX-275-0602 (TRIO025) Date: 11 Sep 2018 Page 42 of 141 Figure 5-8 (Wrangle 2013) Clinical. The combination of entinostat and azacitidine has shown promise in the treatment of advanced NSCLC, with a 100% response rate in the J1353 trial. This suggests that the combination of these two agents may be a highly effective treatment for NSCLC. However, the use of entinostat in combination with other immune checkpoint inhibitors, such as PD-1 or PDL-1, has not yet been studied in a large-scale Phase 3 trial. The Phase 3 trial is currently in the planning stages, with the goal of assessing the safety and efficacy of entinostat in combination with a PD-1 or PDL-1 inhibitor in a large patient population. Product: Entinostat Protocol Number: SNDX-275-0602 (TRIO025) Date: 11 Sep 2018 Page 43 of 141 Figure 5-9 CONFIDENTIAL SYNDAX PHARMACEUTICALS The combination of entinostat and azacitidine has shown promise in the treatment of advanced NSCLC, with a 100% response rate in the J1353 trial. This suggests that the combination of these two agents may be a highly effective treatment for NSCLC. However, the use of entinostat in combination with other immune checkpoint inhibitors, such as PD-1 or PDL-1, has not yet been studied in a large-scale Phase 3 trial. The Phase 3 trial is currently in the planning stages, with the goal of assessing the safety and efficacy of entinostat in combination with a PD-1 or PDL-1 inhibitor in a large patient population. Product: Entinostat Protocol Number: SNDX-275-0602 (TRIO025) Date: 11 Sep 2018 Page 44 of 141 Figure 5-9 (Wrangle 2013) Clinical. The combination of entinostat and azacitidine has shown promise in the treatment of advanced NSCLC, with a 100% response rate in the J1353 trial. This suggests that the combination of these two agents may be a highly effective treatment for NSCLC. However, the use of entinostat in combination with other immune checkpoint inhibitors, such as PD-1 or PDL-1, has not yet been studied in a large-scale Phase 3 trial. The Phase 3 trial is currently in the planning stages, with the goal of assessing the safety and efficacy of entinostat in combination with a PD-1 or PDL-1 inhibitor in a large patient population. Product: Entinostat Protocol Number: SNDX-275-0602 (TRIO025) Date: 11 Sep 2018 Page 45 of 141 Figure 5-10 CONFIDENTIAL SYNDAX PHARMACEUTICALS The combination of entinostat and azacitidine has shown promise in the treatment of advanced NSCLC, with a 100% response rate in the J1353 trial. This suggests that the combination of these two agents may be a highly effective treatment for NSCLC. However, the use of entinostat in combination with other immune checkpoint inhibitors, such as PD-1 or PDL-1, has not yet been studied in a large-scale Phase 3 trial. The Phase 3 trial is currently in the planning stages, with the goal of assessing