Study of DCC-3084 in Participants With Advanced Malignancies Driven by the Mitogen-Activated Protein Kinase (MAPK) Pathway
- Conditions
- Advanced Solid TumorRAF MutationRAS MutationNF1 MutationNon-Small Cell Lung CancerPancreatic Ductal AdenocarcinomaMelanomaBRAF Gene MutationCRAF Gene MutationCastration-Resistant Prostate Cancer (CRPC)
- Interventions
- Registration Number
- NCT06287463
- Lead Sponsor
- Deciphera Pharmaceuticals, LLC
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 140
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
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description DCC-3084 Module A Escalation Phase (ModA Part 1) DCC-3084 Participants will receive DCC-3084 in ModA Part 1, Escalation Phase. DCC-3084 Module A Expansion Phase (ModA Part 2) DCC-3084 Participants will receive DCC-3084 in ModA Part 2, Expansion Phase.
- Primary Outcome Measures
Name Time Method Number of Participants with Dose-limiting Toxicities (DLTs) (ModA Part 1) Cycle 1 (28 days) DLTs reported during ModA Part 1.
Objective Response Rate (ORR) (ModA Part 2) Start of Therapy to Progressive Disease (PD), Death Due to Any Cause, or Start of New Antitumor Therapy (Estimated up to 24 months) ORR is the percentage of participants with confirmed complete or partial remission based on indication specific criteria as defined in the protocol.
- Secondary Outcome Measures
Name Time Method ORR (ModA Part 1) Start of Therapy to PD, Death Due to Any Cause, or Start of New Antitumor Therapy (Estimated up to 24 months) ORR is the percentage of participants with confirmed complete or partial remission based on indication specific criteria as defined in the protocol.
Overall Survival (OS) (ModA Part 1 and 2) Start of Therapy to Death Due to Any Cause (Estimated up to 36 months) OS is the time from start of therapy to death from any cause.
Progression-Free Survival (PFS) (ModA Part 1 and 2) Start of Therapy to PD or Death Due to Any Cause (Estimated up to 24 months) PFS is the time from start of therapy to PD or death due to any cause.
Pharmacokinetics (PK): Maximum observed plasma drug concentration (Cmax) (ModA Part 1 and 2) Predose up to 12 hours postdose Cmax (ModA Part 1 and 2)
Trial Locations
- Locations (9)
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Southern California - Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
SCRI HealthONE
🇺🇸Denver, Colorado, United States
SCRI Florida Cancer Specialists
🇺🇸Orlando, Florida, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
NEXT Oncology Virginia
🇺🇸Fairfax, Virginia, United States