Phase 1/2 Study of Mocetinostat and Durvalumab in Patients With Advanced Solid Tumors and NSCLC

Toxicities were graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Any of the following events considered to be causally related to treatment with mocetinostat in combination with durvalumab that occurred during Phase 1 were considered a DLT: * Any Grade 4 immune-related adverse event (irAE) * Grade 3 or greater colitis * Grade 3 or greater noninfectious pneumonitis * Grade 2 pneumonitis that did not resolve to ≤ Grade 1 within 3 days of the initiation of maximal supportive care * Grade 3 irAE (excluding colitis or pneumonitis) that: * Did not resolve to Grade 2 within 3 days after onset of the event despite optimal medical management including systemic corticosteroids, or * Did not resolve to Grade ≤1 or Baseline within 14 days * Liver transaminase elevation \>8×upper limit of normal (ULN) or total bilirubin \>5×ULN * Grade 3 or greater non-irAE, except nausea, vomiting, anorexia, dehydration, or diarrhea

Time frame: 28 days

Population: DLT Evaluable Population - Participant must have either been on study for one full cycle and have received treatment with durvalumab and at least 9 of 12 scheduled mocetinostat doses (75%) in Cycle 1 or have experienced a DLT in Cycle 1.

Objective Response Rate (ORR) was defined as the number of participants documented to have a confirmed Complete Response (CR) or Partial Response (PR). Complete Response was defined as the complete disappearance of all target lesions with the exception of nodal disease. Partial Response was defined at least a 30% decrease in the sum of diameters of target measurable lesions. Responses were determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Participants without response data were counted as non-responders. Inferential statistical analyses were conducted for Phase 2 only, as efficacy was not part of the Phase 1 objectives.

Time frame: Up to approximately 10 months

Population: Clinical Activity Evaluable Population - The Clinical Activity Evaluable Population was defined as all participants who had at least one on-study disease assessment or discontinued from treatment for progressive disease (PD).

Time frame: 1 year

Population: Modified Intent-to-Treat Population (mITT) - The mITT Population was defined as all participants who received treatment with both mocetinostat and durvalumab on this study.

Clinical benefit rate (CBR) was defined as the number of participants documented to have a confirmed Complete Response (CR), Partial Response (PR), or Stable Disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Participants who were not be able to be assessed for response were counted as non-responders.

Time frame: Up to approximately 10 months

Population: Clinical Activity Evaluable Population - The Clinical Activity Evaluable Population was defined as all participants who had at least one on-study disease assessment or discontinued from treatment for progressive disease (PD).

Plasma concentration of Durvalumab was evaluated. All participants received the same Durvalumab dose regardless of Mocetinistat dose group.

Time frame: Cycle 1 Day 1 pre-dose + end of infusion, Cycle 1 Day 15 pre-mocetinostat dose, Cycle 2 Day 1 pre-dose, Cycle 3 Day 1 pre-dose, Cycle 4 Day 1 pre-dose + end of infusion, Cycle 7 Day 1 pre-dose + 90 days after participant's last dose (Up to max 133 weeks)

Population: Pharmacokinetic Evaluable Population - The Pharmacokinetic (PK) Evaluable Population was defined as all patients who had PK concentration data collected for mocetinostat or durvalumab. Participants were combined for analysis of mocetinistat concentrations, as prespecified in the analysis shells, based on the actual dose of mocetinistat received in each phase of the study. Pharmacokinetic measures at 3 and 7 hours post dose on Cycle 1 Day 1 were only planned for Phase 1.

Time frame: Cycle 1 Day 1 pre-dose, 1, 3, and 7 hours post-dose, Cycle 1 Day 15 pre-dose and 1 hour post-dose, Cycle 2 Day 1 pre-dose and 1 hour post-dose, Cycle 3 Day 1 pre-dose and 1 hour post-dose and Cycle 7 Day 1 pre-dose (each cycle is 28 days)

Population: Pharmacokinetic Evaluable Population - The Pharmacokinetic (PK) Evaluable Population was defined as all patients who had PK concentration data collected for mocetinostat or durvalumab. Participants were combined for analysis of mocetinistat concentrations, as prespecified in the analysis shells, based on the actual dose of mocetinistat received in each phase of the study. Pharmacokinetic measures at 3 and 7 hours post dose on Cycle 1 Day 1 were only planned for Phase 1.

DR was defined as the time in days from date of the first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the first documentation of objective Progressive Disease (PD) or to death due to any cause in the absence of documented PD. DR was only calculated for the subgroup of participants who achieved a Best Overall Response of CR or PR and was presented for responses assessed by Investigator's assessment. Data is displayed for Phase 2 only, as no participants experienced an objective response (CR or PR) during Phase 1.

Time frame: Up to approximately 10 months

Population: Clinical Activity Evaluable Population (Subgroup of Responders) - Duration of response was only calculated for the subgroup of participants achieving a CR or PR.

Time frame: Day 1 to 28 days after last dose of study treatment (up to a maximum of 125 weeks in phase 1 and a maximum of 92 weeks in phase 2)

Population: Safety Population - The Safety population was defined as all participants who received at least 1 dose of either mocetinostat or durvalumab.

Time frame: Up to approximately 10 months

Population: ADA Evaluable Population - The ADA Evaluable Population was defined as all patients who received at least 1 dose of either durvalumab or mocetinostat for whom ADA results were available.

Time frame: Baseline

Population: Modified Intent-to-Treat Population (mITT) - The mITT Population was defined as all participants who received treatment with both mocetinostat and durvalumab on this study.

OS was defined as the time from first dose of study treatment to the date of death due to any cause.

Time frame: From date of first study treatment until death due to any cause (up to 42 months)

Population: Modified Intent-to-Treat Population (mITT) - The mITT Population was defined as all participants who received treatment with both mocetinostat and durvalumab on this study.

Progression-free survival (PFS) was defined as the time from date of first study treatment to first Progressive Disease (PD) or death due to any cause in the absence of documented PD per RECIST v1.1

Time frame: Randomization until progressive disease or death due to any cause (up to 42 months)

Population: Modified Intent-to-Treat Population (mITT) - The mITT Population was defined as all participants who received treatment with both mocetinostat and durvalumab on this study.