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

Sponsor

Deciphera Pharmaceuticals LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05957367

Collaborator

Pfizer (Industry)

170

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer GIST	Drug: DCC-3116 Drug: Ripretinib Drug: Cetuximab Drug: Encorafenib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

170 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2027

Anticipated Study Completion Date :

Jun 1, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Incidence of Adverse Events (Escalation Phase) [Approximately 24 months]
Identify the observed adverse events and serious adverse events associated with DCC-3116 in combination with cetuximab and encorafenib or ripretinib.
Recommended Phase 2 Doses (RP2D) (Escalation Phase) [Approximately 18 months]
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.
Objective response rate (ORR) (Expansion Phase) [Approximately 24 months]
Proportion of participants who achieve CR or PR per RECIST (or mRECIST, as applicable) v1.1.

Secondary Outcome Measures

Duration of response (DoR) (Escalation Phase) [Approximately 24 months]
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.
Disease Control Rate (DCR) (Escalation Phase) [Approximately 24 months]
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.
Time to response (Escalation Phase) [Approximately 24 months]
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.
Progression-free survival (PFS) (Escalation Phase) [Approximately 24 months]
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.
Overall Survival (OS) [Approximately 48 months]
OS is defined as the time from initiation of treatment until death.
Maximum observed concentration (Cmax) [Predose and up to 12 hours postdose]
Measure the maximum observed concentration of DCC-3116 combinations.
Time to maximum observed concentration (Tmax) [Predose and up to 12 hours postdose]
Measure the time to maximum plasma concentration of DCC-3116 combinations.
Minimum observed concentration (Cmin) [Predose and up to 12 hours postdose]
Measure the minimum observed concentration of DCC-3116 combinations.
Area under the concentration-time curve (AUC) [Predose and up to 12 hours postdose]
Measure the AUC of DCC-3116 combinations.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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)
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)
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
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