study of dcc-3084 in participants with advanced malignancies driven by the mitogen-activated protein kinase (mapk) pathway

Conditions: Advanced Solid Tumor; RAF Mutation; RAS Mutation; NF1 Mutation; Non-Small Cell Lung Cancer; Pancreatic Ductal Adenocarcinoma; Melanoma; BRAF Gene Mutation; CRAF Gene Mutation; Castration-Resistant Prostate Cancer (CRPC)

Summary: this is a multicenter, phase 1/2 clinical trial to evaluate dcc-3084 alone or in combination with other cancer therapies in participants with advanced cancers. module a will enroll participants with advanced/metastatic solid tumors. additional modules exploring other cancers may be added to the master protocol at a later date. each module will be conducted in 2 parts: part 1 (dose escalation) and part 2 (dose expansion).


Eligibility criteria:
inclusion criteria: general inclusion criteria moda part 1 and 2: * able to take oral medication * if a female is of childbearing potential, must have a negative pregnancy test prior to enrollment and all participants agree to follow the contraception requirements * adequate organ function and electrolytes * eastern cooperative oncology group performance status (ecog-ps) of 0 to 1 at screening * has a life expectancy of more than 6 months * in addition to these general inclusion criteria, participants must meet all the module cohort-specific inclusion criteria inclusion criteria moda part 1 cohort specific: * pathologically confirmed diagnosis of solid cancer and documentation of kirsten rat sarcoma (kras), harvey rat sarcoma virus (hras), neuroblastoma ras viral oncogene homolog (nras), v-raf murine sarcoma viral oncogene homolog b1 (braf), v-raf murine sarcoma viral oncogene homolog c1(craf), and/or neurofibromatosis 1 (nf1) mutation * have exhausted all available standard of care therapies that are known to provide benefit for the participant's condition, as judged by the investigator inclusion criteria moda part 2 cohort specific: * documented braf gene mutation * pathologically confirmed diagnosis with pd after at least one prior line of therapy in the advanced or metastatic setting exclusion criteria: general exclusion criteria moda part 1 and 2: * prior treatment with certain braf dimer inhibitors * female participant is pregnant or lactating * received any prior or concurrent medications or therapies known to be prohibited with dcc-3084 within 14 days * received any prior antitumor therapy or any investigational therapy within a specified timeframe prior to first dose of dcc-3084 * known allergy or hypersensitivity to any component of the study drug * invasive malignancy within 2 years prior to the first dose of study drug other than the study indication or specific types of cancer treated with curative intent * have not recovered from all clinically relevant toxicities from prior therapy * impaired cardiac function * history of recent thrombotic or embolic events * malabsorption syndrome or other illness that could affect oral absorption * major surgery within 28 days of the first dose of study drug * in addition to the general exclusion criteria, participants will also be excluded based on the cohort-specific exclusion criteria exclusion criteria: module a part 2 cohort specific: • has known co-occurring mutation of kras, hras, nras, nf1, epidermal growth factor receptor, phosphoinositide-3-kinase, catalytic, alpha polypeptide (pi3kca), or phosphatase and tensin homolog deleted on chromosome 10 (pten)

Keywords: advanced malignancies