A Phase 1/2 Study of DCC-3116 in Patients With MAPK Pathway Mutant Solid Tumors

Prior treatment

• Must not have received the following within the specified time periods prior to the first dose of study drug: a. Prior therapies (anticancer or therapies given for other reasons) that are known strong or moderate inhibitors or inducers of CYP3A4 or P-gp (refer to Section 9.8.3) including certain herbal medications (eg, St. John’s Wort): 14 days or 5× the half-life of the medication (whichever is longer) b. All other prior anticancer therapies or any therapy that is investigational for the participant’s condition with a known safety and PK profile: 14 days or 5× the half-life of the medication (whichever is shorter) c. Investigational therapies with unknown safety and PK profile: 28 days. If there is enough data on the investigational therapy to assess the risk for drug-drug interactions and late toxicities of prior therapy as low, the Sponsor’s Medical Monitor may approve a shorter washout of 14 days d. Grapefruit or grapefruit juice: 14 days
• Has a prior or concurrent malignancy that requires treatment or is expected to require treatment for active cancer during this study. Hormonal maintenance after treatment is allowed
• Have not recovered from all toxicities from prior therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 to Grade ≤1 or participant baseline prior to first dose of study drug (excluding alopecia). Participant baseline is defined as no change in severity grade within 28 days prior to signed informed consent
• Presence or history of central nervous system (CNS) metastases or leptomeningeal disease, with the following exceptions: • If there is a history of brain metastases, they must be stable for at least 6 months (no new metastases and no evidence of progression of known metastases at Screening compared to historical scans) • If there is a history of leptomeningeal disease, it must have cleared at least 6 months prior to Screening • If there are neurologic symptoms consistent with CNS disease, they must not be new or increasing in severity over at least 6 months prior to Screening • If there is a history of CNS metastasis or leptomeningeal disease, it must not require continued therapy
• New York Heart Association Class III or IV heart disease, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, congestive heart failure, or myocardial infarction within 6 months prior to the first dose of study drug

Lab values

• Prolongation of the QT interval corrected by Fridericia’s formula (QTcF) based on repeated demonstration of QTcF >450 ms in males or >470 ms in females at Screening or history of long QT syndrome

• Male or female participant at least 18 years of age
• Have progressed despite standard therapies, or for whom conventional therapy is not considered effective or tolerable, as judged by the Investigator
• Must provide a fresh tumor biopsy from a primary or metastatic cancer lesion if it can be biopsied with acceptable risk as determined by the Investigator during the Screening Period
• Must have at least 1 measurable lesion according to RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status at Screening of 0 to 1