Clinical trial NCT06818812: A Study to Evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
Official title: A Phase 1, Open-Label, Multicenter Study of INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumors
Keywords: INCB186748
KRASG12D Mutation
pancreatic ductal adenocarcinoma (PDAC)
colorectal cancer (CRC)
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2025-02-10
Enrollment: 308
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: The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation.


Eligibility criteria: Inclusion Criteria:

* ≥18 years old.
* Locally advanced or metastatic solid tumor with KRAS G12D mutation.
* For Part 1 and Part 2 Combination Group 1: Disease progression on or after prior standard treatment, or intolerance to or ineligibility for standard treatment, or no standard available treatment to improve the disease outcome.
* For Part 2 Combination Groups 2 and 3: No more than 1 prior standard treatment.
* Cohort-specific requirements as follows:

  * Parts 1a and 1d: histologically or cytologically confirmed malignant solid tumor of any tissue origin.
  * Part 1b

    * Disease Group 1: diagnosis of PDAC and at least 1 but no more than 2 prior standard systemic regimens for pancreatic cancer.
    * Disease Group 2: diagnosis of CRC.
  * Part 1c: Confirmed diagnosis of PDAC or CRC.
  * Parts 2a and 2b

    * Combination Group 1 (INCB186748 in combination with cetuximab):

      * Diagnosis of PDAC or
      * Diagnosis of CRC and ∘ Prior treatment in the advanced setting with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan and

        * In Part 2a: ≤ 3 prior standard regimens.
        * In Part 2b: ≤ 2 prior standard regimens.
    * Combination Group 2 (INCB186748 in combination with GEMNabP) and
    * Combination Group 3 (INCB186748 in combination with mFOLFIRINOX):

      * Diagnosis of PDAC.
      * ≤ 1 prior standard systemic regimen for pancreatic cancer.
* Measurable disease according to RECIST v1.1.
* ECOG performance status score of 0 or 1.

Exclusion Criteria:

* Prior treatment with any KRAS inhibitor.
* Known additional invasive malignancy within 1 year of the first dose of study drug.
* History of organ transplant, including allogeneic stem cell transplantation.
* Significant, uncontrolled medical condition.
* History or presence of an ECG abnormality.
* Inadequate organ function.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Primary outcomes:
measure: Number of participants with Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 12 months and 60 days
measure: Number of participants with TEAEs leading to dose modification or discontinuation
timeFrame: Up to approximately 12 months and 60 days
Secondary outcomes:
measure: INCB186748 pharmacokinetic (PK) in Plasma
timeFrame: Up to approximately 12 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 12 months
measure: Disease Control Response (DCR)
timeFrame: Up to approximately 12 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 12 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Healthcare Hematology-Oncology
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institue At Healthone
state: Colorado
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
state: Maryland
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Philadelphia
country: United States
facility: Jefferson University Hospitals
state: Pennsylvania
city: Nashville
country: United States
facility: Scri Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: