A Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies

A Master Protocol for the Multi-Cohort, Phase 1/2 Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies

This is a Phase 1/2, multicenter, open-label (unless otherwise specified in a combination-specific module) study of DCC-3116 in combination with anticancer therapies. Modules within the master protocol are defined according to different combinations of DCC-3116 with other anticancer agents.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; GIST
• Intervention / Treatment: Drug: DCC-3116; Drug: Cetuximab; Drug: Encorafenib; Drug: Ripretinib

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Team; Phone Number: 785-830-2100; Email: Clinicaltrials@deciphera.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Department of Medicine-Hematology/Oncology
      • Contact: Jacqueline Banuelos; Phone Number: 16108 310-869-7014; Email: jbanuelosmurillo@mednet.ucla.edu
      • Principal Investigator: Arun Singh, MD
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • Sylvester Comprehensive Cancer Center
      • Contact: Nailet Bestard; Phone Number: 305-243-8173; Email: nxr518@med.miami.edu
      • Principal Investigator: Jonathan C Trent, MD, PhD
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • Start Midwest
      • Contact: Julie Burns; Phone Number: 616-954-5559; Email: julie.burns@startmidwest.com
      • Principal Investigator: Sreenivasa Chandana, M.D., Ph.D.
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
      • Contact: Phase 1 Screening; Phone Number: 212-731-5654; Email: Phase1Screening@nyulangone.org
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center - Main Campus
      • Principal Investigator: Ping Chi, MD, PhD
      • Contact: Pragya Khadka; Email: khadkap1@mskcc.org
      • Contact: Melessa Hardayal; Email: hardayam@mskcc.org
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Taussig Cancer Center
      • Contact: Cancer Answer; Phone Number: 216-444-7923; Email: canceranswer@ccf.org
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Knight Cancer Institute Clinical Trials; Phone Number: 503-494-1080; Email: trials@ohsu.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Principal Investigator: Margaret von Mehren, MD
      • Contact: Refiola Memushi; Phone Number: 215-728-3564; Email: Refiola.Memushi@fccc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female ≥18 years of age

• Module A: Part 1 and Part 2:

  • Pathologically confirmed diagnosis of CRC with BRAF V600E mutation.
  • Must have received at least 1 and not more than 2 lines of prior systemic therapy in the advanced or metastatic setting.
  • Must not have received prior treatment with an epidermal growth factor receptor or BRAF inhibitor

• Module B: Only for Part 1 (Safety/Dose-finding):

  • Pathologically confirmed diagnosis of GIST with a KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutation.
  • Must have progressed on at least one approved systemic regimen given in the locally advanced or metastatic setting or have documented intolerance to it
  • Must not have received prior ripretinib treatment

• Module B: Only for Part 2 (Expansion)

  • Pathologically confirmed GIST with documented mutation in KIT exon 11
  • Must have progressed on imatinib given in the locally advanced or metastatic setting or have been intolerant to imatinib and may not have received additional systemic therapy for GIST.
• Measurable disease.
• Must have a life expectancy of more than 3 months and an ECOG performance status of 0-1
• Adequate organ function and bone marrow reserve based on laboratory assessments performed at Screening
• Must provide a fresh tumor biopsy and an archival tumor tissue sample, if available.
• Must agree to provide an on treatment biopsy

Exclusion Criteria:

• Must not have received the following within the specified time periods prior to the first dose of study drug:

  1. Medications, including anticancer therapies, that are known strong or moderate inhibitors or inducers of CYP3A4 or P-glycoprotein (P-gp) including certain herbal medications (eg, St. John's wort): 14 days or 5×the half-life of the medication (whichever is longer)
  2. Other anticancer therapies and any investigational therapies with a known safety and PK profile: 14 days or 5×the half-life of the medication (whichever is shorter)
  3. Investigational therapies with unknown safety and PK profile: 28 days. If there is enough data on the investigational therapy to assess the risk for drug-drug interactions and late toxicities of prior therapy as low, the Sponsor's Medical Monitor may approve a shorter washout of 14 days
  4. Grapefruit or grapefruit juice: 14 days
• Have not recovered from all clinically relevant toxicities from prior therapy
• New York Heart Association Class III or IV heart disease, active ischemia, or any other uncontrolled cardiac condition, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, congestive heart failure, or myocardial infarction within 6 months prior to the first dose of study drug
• Symptomatic central nervous system (CNS) metastases or presence of leptomeningeal disease
• Malabsorption syndrome
• Bone disease that requires ongoing treatment or has required treatment
• Radiation for indications other than bone disease must have been completed 4 weeks prior to first dose of study drug, unless it consisted of limited field palliative radiation, including whole brain radiation, which must have been completed at least 2 weeks prior to first dose of study drug
• Major surgery within 4 weeks of the first dose of study drug
• Active HIV, Hepatitis B or Hepatitis C infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (Part 1, Module A); DCC-3116 tablets in escalating dose cohorts in 28-day cycles will be administered in combination with encorafenib once daily (QD) and cetuximab once every 2 weeks (Q2W).	Drug: DCC-3116; Oral Tablet Formulation; Drug: Cetuximab; Solution for Injection; Other Names: Erbitux; Drug: Encorafenib; Oral capsule formulation; Other Names: Braftovi
Experimental: Expansion (Part 2, Module A); DCC-3116 tablets will be administered in combination with encorafenib and cetuximab in 28-day cycles to evaluate preliminary efficacy in participants with 2nd- or 3rd-line BRAF V600E mutated colorectal cancer (CRC).	Drug: DCC-3116; Oral Tablet Formulation; Drug: Cetuximab; Solution for Injection; Other Names: Erbitux; Drug: Encorafenib; Oral capsule formulation; Other Names: Braftovi
Experimental: Dose Escalation (Part 1, Module B); DCC-3116 tablets in escalating dose cohorts in 28-day cycles will be administered in combination with ripretinib once daily (QD).	Drug: DCC-3116; Oral Tablet Formulation; Drug: Ripretinib; Oral Tablet Formulation; Other Names: QINLOCK, DCC-2618
Experimental: Expansion (Part 2, Module B); DCC-3116 tablets will be administered in combination with ripretinib in 28-day cycles to evaluate preliminary efficacy in participants with 2nd-line advanced gastrointestinal stromal tumor (GIST).	Drug: DCC-3116; Oral Tablet Formulation; Drug: Ripretinib; Oral Tablet Formulation; Other Names: QINLOCK, DCC-2618

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (Escalation Phase)	Identify the observed adverse events and serious adverse events associated with DCC-3116 in combination with cetuximab and encorafenib or ripretinib.	Approximately 24 months
Recommended Phase 2 Doses (RP2D) (Escalation Phase)	Identify the dose-limiting toxicities for each dose level tested and determine the recommended Phase 2 doses of DCC-3116 in combination with cetuximab and encorafenib or ripretinib.	Approximately 18 months
Objective response rate (ORR) (Expansion Phase)	Proportion of participants who achieve CR or PR per RECIST (or mRECIST, as applicable) v1.1.	Approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DoR) (Escalation Phase)	DoR is defined as the time interval from the time that the measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that the progressive disease is objectively documented or death, whichever occurs first.	Approximately 24 months
Disease Control Rate (DCR) (Escalation Phase)	The DCR is defined as the proportion of participants who achieve CR, PR, or stable disease [SD] at the specified time point per RECIST (or mRECIST, as applicable) v1.1.	Approximately 24 months
Time to response (Escalation Phase)	Time to response is defined as the time from initiation of treatment until the first assessment demonstrating CR or PR per RECIST (or mRECIST, as applicable) v1.1.	Approximately 24 months
Progression-free survival (PFS) (Escalation Phase)	PFS is defined as the time from initiation of treatment until documented disease progression per RECIST (or mRECIST, as applicable) v1.1 or death, whichever occurs first.	Approximately 24 months
Overall Survival (OS)	OS is defined as the time from initiation of treatment until death.	Approximately 48 months
Maximum observed concentration (Cmax)	Measure the maximum observed concentration of DCC-3116 combinations.	Predose and up to 12 hours postdose
Time to maximum observed concentration (Tmax)	Measure the time to maximum plasma concentration of DCC-3116 combinations.	Predose and up to 12 hours postdose
Minimum observed concentration (Cmin)	Measure the minimum observed concentration of DCC-3116 combinations.	Predose and up to 12 hours postdose
Area under the concentration-time curve (AUC)	Measure the AUC of DCC-3116 combinations.	Predose and up to 12 hours postdose

Collaborators and Investigators

• Sponsor: Deciphera Pharmaceuticals LLC
• Collaborators: Pfizer
• Investigators: Study Director: Clinical Team, Deciphera Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: July 14, 2023
• First Submitted That Met QC Criteria: July 14, 2023
• First Posted (Actual): July 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: CRC; cetuximab; Advanced colorectal cancer; encorafenib; DCC-3116; gastrointestinal stromal tumors; ripretinib; Advanced gastrointestinal stromal tumors
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: DCC-3116-01-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No