Solid Tumors
Conditions
Keywords
INCB186748, KRASG12D Mutation, pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC)
Brief summary
The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation.
Interventions
DRUGINCB186748
INCB186748 will be administered at protocol defined dose.
DRUGCetuximab
Cetuximab will be administered at protocol defined dose.
DRUGGEMNabP
GEMNabP will be administered at protocol defined dose.
DRUGmFOLFIRINOX
mFOLFIRINOX will be administered at protocol defined dose.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Dose Limiting Toxicities (DLTs) | Up to 28 days | Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol. |
| Number of participants with Treatment-emergent Adverse Events (TEAEs) | Up to approximately 12 months and 60 days | Defined as adverse events reported for the first time or worsening of a pre-existing event occurring after the first dose of study drug up to 30 days (for INCB186748 as monotherapy and in combination with GEMNabP or mFOLFIRINOX) and 60 days (for INCB186748 in combination with cetuximab) after the last dose of INCB186748. |
| Number of participants with TEAEs leading to dose modification or discontinuation | Up to approximately 12 months and 60 days | Number of participants with TEAEs leading to dose modification or discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| INCB186748 pharmacokinetic (PK) in Plasma | Up to approximately 12 months | INCB186748 concentration in plasma. |
| Objective Response Rate (ORR) | Up to approximately 12 months | Defined as having a best overall Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1. |
| Disease Control Response (DCR) | Up to approximately 12 months | Defined as having a best overall response of CR, PR, or Stable Disease (SD) as determined by the investigator by radiographic disease assessment according to RECIST v1.1. |
| Duration of Response (DOR) | Up to approximately 12 months | Defined as the time from earliest date of disease response (Completed Response or Partial Response) until earliest date of disease progression as determined by the investigator by radiographic disease assessment according to RECIST v1.1 or death due to any cause if occurring sooner than progression. |
Countries
United States
Contacts
STUDY_DIRECTORIncyte Medical Monitor
Incyte Corporation
Outcome results
None listed