A Study to Evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation

NCT06818812 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: INCB186748-1012024-519018-30-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation.

Conditions

Solid Tumors

Keywords

INCB186748; KRASG12D Mutation; pancreatic ductal adenocarcinoma (PDAC); colorectal cancer (CRC)

Outcome Measures

Primary Outcomes (3)

• Number of participants with Dose Limiting Toxicities (DLTs)

  Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.

  Up to 28 days

• Number of participants with Treatment-emergent Adverse Events (TEAEs)

  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.

  Up to approximately 12 months and 60 days

• Number of participants with TEAEs leading to dose modification or discontinuation

  Number of participants with TEAEs leading to dose modification or discontinuation.

  Up to approximately 12 months and 60 days

Secondary Outcomes (4)

• INCB186748 pharmacokinetic (PK) in Plasma

  Up to approximately 12 months

• Objective Response Rate (ORR)

  Up to approximately 12 months

• Disease Control Response (DCR)

  Up to approximately 12 months

• Duration of Response (DOR)

  Up to approximately 12 months

Study Arms (6)

Part 1a: Dose Escalation monotherapy

EXPERIMENTAL

INCB186748 at the protocol-defined dose strength based on cohort assignment.

Drug: INCB186748

Part 1b: Dose Expansion monotherapy

EXPERIMENTAL

INCB186748 at the protocol-defined dose strength based on cohort assignment.

Drug: INCB186748

Part 1c: Pharmacodynamic cohort

EXPERIMENTAL

INCB186748 at the protocol-defined dose strength based on cohort assignment.

Drug: INCB186748

Part 1d: Food-Effect

EXPERIMENTAL

Evaluate food effect on drug exposure as defined in the protocol.

Drug: INCB186748

Part 2a: Dose Escalation combination

EXPERIMENTAL

INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.

Drug: INCB186748; Drug: Cetuximab; Drug: GEMNabP; Drug: mFOLFIRINOX

Part 2b: Dose Expansion combination

EXPERIMENTAL

INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.

Drug: INCB186748; Drug: Cetuximab; Drug: GEMNabP; Drug: mFOLFIRINOX

Interventions

INCB186748 DRUG

INCB186748 will be administered at protocol defined dose.

Part 1a: Dose Escalation monotherapy; Part 1b: Dose Expansion monotherapy; Part 1c: Pharmacodynamic cohort; Part 1d: Food-Effect; Part 2a: Dose Escalation combination; Part 2b: Dose Expansion combination

Cetuximab DRUG

Cetuximab will be administered at protocol defined dose.

Part 2a: Dose Escalation combination; Part 2b: Dose Expansion combination

GEMNabP DRUG

GEMNabP will be administered at protocol defined dose.

Part 2a: Dose Escalation combination; Part 2b: Dose Expansion combination

mFOLFIRINOX DRUG

mFOLFIRINOX will be administered at protocol defined dose.

Part 2a: Dose Escalation combination; Part 2b: Dose Expansion combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (9)

UCLA Healthcare Hematology-Oncology

Santa Monica, California, 90404, United States

Location

Sarah Cannon Research Institue At Healthone

Denver, Colorado, 80218, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins

Baltimore, Maryland, 21287-7049, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Jefferson University Hospitals

Philadelphia, Pennsylvania, 19107, United States

Location

Scri Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• A Study to Evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Incyte Medical Monitor

  Incyte Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2025
• First Posted: February 10, 2025
• Study Start: March 27, 2025
• Primary Completion (Estimated): March 27, 2027
• Study Completion (Estimated): March 27, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)