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

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06287463
• Other study ID #: DCC-3084-01-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 14, 2024
• Est. completion date: August 2027

Study information

• Verified date: May 2024
• Source: Deciphera Pharmaceuticals LLC
• Contact: Clinical Team
• Phone: 785-830-2100
• Email: clinicaltrials[@]deciphera.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: August 2027
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

General Inclusion Criteria ModA Part 1 and 2:

• Able to provide a fresh tumor biopsy from a primary or metastatic cancer lesion and an archival tumor tissue sample, if available

• 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)

Related Conditions & MeSH terms

• Advanced Solid Tumor
• BRAF Gene Mutation
• Melanoma
• Neoplasms
• Non-Small Cell Lung Cancer
• Pancreatic Ductal Adenocarcinoma
• RAS Mutation

Intervention

Drug:
• DCC-3084
Administered orally

Locations

Country	Name	City	State
United States	NEXT Oncology Virginia	Fairfax	Virginia
United States	University of Southern California - Norris Comprehensive Cancer Center	Los Angeles	California
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Deciphera Pharmaceuticals LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose-limiting Toxicities (DLTs) (ModA Part 1)	DLTs reported during ModA Part 1.	Cycle 1 (28 days)
Primary	Objective Response Rate (ORR) (ModA Part 2)	ORR is the percentage of participants with confirmed complete or partial remission based on indication specific criteria as defined in the protocol.	Start of Therapy to Progressive Disease (PD), Death Due to Any Cause, or Start of New Antitumor Therapy (Estimated up to 24 months)
Secondary	ORR (ModA Part 1)	ORR is the percentage of participants with confirmed complete or partial remission based on indication specific criteria as defined in the protocol.	Start of Therapy to PD, Death Due to Any Cause, or Start of New Antitumor Therapy (Estimated up to 24 months)
Secondary	Progression-Free Survival (PFS) (ModA Part 1 and 2)	PFS is the time from start of therapy to PD or death due to any cause.	Start of Therapy to PD or Death Due to Any Cause (Estimated up to 24 months)
Secondary	Overall Survival (OS) (ModA Part 1 and 2)	OS is the time from start of therapy to death from any cause.	Start of Therapy to Death Due to Any Cause (Estimated up to 36 months)
Secondary	Pharmacokinetics (PK): Maximum observed plasma drug concentration (Cmax) (ModA Part 1 and 2)	Cmax (ModA Part 1 and 2)	Predose up to 12 hours postdose