Study of DCC-3084 in Participants With Advanced Malignancies Driven by the Mitogen-Activated Protein Kinase (MAPK) Pathway

Deciphera Pharmaceuticals, LLC

Status and phase: Active, not recruiting; Phase 2; Phase 1

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

Treatments: Drug: DCC-3084

Study type: Interventional

Funder types: Industry

Identifiers

NCT06287463

DCC-3084-01-001

Details and patient eligibility

About

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).

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

DCC-3084 Module A Escalation Phase (ModA Part 1)

Experimental group

Description:

Participants will receive DCC-3084 in ModA Part 1, Escalation Phase.

Treatment:

Drug: DCC-3084

DCC-3084 Module A Expansion Phase (ModA Part 2)

Experimental group

Description:

Participants will receive DCC-3084 in ModA Part 2, Expansion Phase.

Treatment:

Drug: DCC-3084