Clinical trial NCT06287463: Study of DCC-3084 in Participants With Advanced Malignancies Driven by the Mitogen-Activated Protein Kinase (MAPK) Pathway
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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)
Keywords: Advanced malignancies
Lead sponsor: Deciphera Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2024-03-01
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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)

Primary outcomes:
measure: Number of Participants with Dose-limiting Toxicities (DLTs) (ModA Part 1)
timeFrame: Cycle 1 (28 days)
measure: Objective Response Rate (ORR) (ModA Part 2)
timeFrame: Start of Therapy to Progressive Disease (PD), Death Due to Any Cause, or Start of New Antitumor Therapy (Estimated up to 24 months)
Secondary outcomes:
measure: ORR (ModA Part 1)
timeFrame: Start of Therapy to PD, Death Due to Any Cause, or Start of New Antitumor Therapy (Estimated up to 24 months)
measure: Progression-Free Survival (PFS) (ModA Part 1 and 2)
timeFrame: Start of Therapy to PD or Death Due to Any Cause (Estimated up to 24 months)
measure: Overall Survival (OS) (ModA Part 1 and 2)
timeFrame: Start of Therapy to Death Due to Any Cause (Estimated up to 36 months)
measure: Pharmacokinetics (PK): Maximum observed plasma drug concentration (Cmax) (ModA Part 1 and 2)
timeFrame: Predose up to 12 hours postdose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California - Norris Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: SCRI HealthONE
state: Colorado
city: Orlando
country: United States
facility: SCRI Florida Cancer Specialists
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology Virginia
state: Virginia
Study officials:
References: