Evaluating DCC-3084 for advanced cancers driven by the MAPK pathway

A Master Protocol for the Multi-Cohort, Open-Label, Phase 1/2 Study of DCC-3084 as Monotherapy and in Combination With Other Antitumor Agents in Participants With Advanced Malignancies Driven by the MAPK Pathway

This study is testing a new cancer drug called DCC-3084 to see if it helps people with advanced solid tumors when used alone or with other treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Deciphera Pharmaceuticals, LLC (industry)
• Locations: 9 sites (Los Angeles, California and 8 other locations)
• Trial ID: NCT06287463 on ClinicalTrials.gov

What this trial studies

This multicenter Phase 1/2 clinical trial aims to assess the safety and efficacy of DCC-3084, both as a standalone treatment and in combination with other cancer therapies, for participants with advanced solid tumors. The trial consists of multiple modules, starting with Module A, which focuses on patients with advanced or metastatic solid tumors. Each module will be divided into two parts: a dose escalation phase to determine the optimal dosage and a dose expansion phase to further evaluate the treatment's effectiveness.

Who should consider this trial

Good fit: Ideal candidates include individuals with advanced solid tumors who have specific mutations in the MAPK pathway and have exhausted standard treatment options.

Not a fit: Patients without advanced malignancies or those who have not undergone prior standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced malignancies driven by specific genetic mutations.

How similar studies have performed: Other studies targeting the MAPK pathway have shown promise, indicating potential for success with this approach.

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)

Where this trial is running

Los Angeles, California and 8 other locations

• University of Southern California - Norris Comprehensive Cancer Center — Los Angeles, California, United States (RECRUITING)
• University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center — San Francisco, California, United States (RECRUITING)
• SCRI HealthONE — Denver, Colorado, United States (RECRUITING)
• SCRI Florida Cancer Specialists — Orlando, Florida, United States (RECRUITING)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
• Roswell Park Comprehensive Cancer Center — Buffalo, New York, United States (RECRUITING)
• SCRI Oncology Partners — Nashville, Tennessee, United States (RECRUITING)
• NEXT Oncology — San Antonio, Texas, United States (RECRUITING)
• NEXT Oncology Virginia — Fairfax, Virginia, United States (RECRUITING)

Study contacts

• Study coordinator: Clinical Team

Conditions: Advanced Solid Tumor, RAF Mutation, RAS Mutation, NF1 Mutation, Non-Small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma, Melanoma, BRAF Gene Mutation