Solid TumorsPhase 1NCT06818812
A Study to Evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
A Phase 1 study testing INCB186748, Cetuximab and GEMNabP in people with Solid Tumors, run by Incyte Corporation at 9 sites in United States.
Trial summary
The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- INCB186748, Cetuximab and GEMNabP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 9 sitesUnited States
- Study dates
- 27 Mar 2025to 27 Mar 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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.
Show all 22Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
Baltimore, Maryland, 21287-7049
Sarah Cannon Research Institue At Healthone
Denver, Colorado, 80218
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Md Anderson Cancer Center
Houston, Texas, 77030
Scri Oncology Partners
Nashville, Tennessee, 37203
Jefferson University Hospitals
Philadelphia, Pennsylvania, 19107
UCLA Healthcare Hematology-Oncology
Santa Monica, California, 90404
Florida Cancer Specialists
Sarasota, Florida, 34232
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase 1, Open-Label, Multicenter Study of INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation.
- Conditions
- Solid Tumors
- Being tested
- INCB186748, Cetuximab, GEMNabP, mFOLFIRINOX
- Keywords
- INCB186748, KRASG12D Mutation, pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC)
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INCB186748Drug
INCB186748 will be administered at protocol defined dose.
CetuximabDrug
Cetuximab will be administered at protocol defined dose.
GEMNabPDrug
GEMNabP will be administered at protocol defined dose.
mFOLFIRINOXDrug
mFOLFIRINOX will be administered at protocol defined dose.
| Study group | Role | What they receive |
|---|---|---|
| Part 1a: Dose Escalation monotherapy | Experimental | INCB186748 at the protocol-defined dose strength based on cohort assignment. Receives: Drug: INCB186748 |
| Part 1b: Dose Expansion monotherapy | Experimental | INCB186748 at the protocol-defined dose strength based on cohort assignment. Receives: Drug: INCB186748 |
| Part 1c: Pharmacodynamic cohort | Experimental | INCB186748 at the protocol-defined dose strength based on cohort assignment. Receives: Drug: INCB186748 |
| Part 1d: Food-Effect | Experimental | Evaluate food effect on drug exposure as defined in the protocol. Receives: Drug: INCB186748 |
| Part 2a: Dose Escalation combination | Experimental | INCB186748 in combination at the protocol-defined dose strength based on cohort assignment. Receives: 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. Receives: Drug: INCB186748; Drug: Cetuximab; Drug: GEMNabP; Drug: mFOLFIRINOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 12 months and 60 days
Secondary outcomes (4)
INCB186748 pharmacokinetic (PK) in Plasma
INCB186748 concentration in plasma.
Measured: Up to approximately 12 months
Objective Response Rate (ORR)
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.
Measured: Up to approximately 12 months
Disease Control Response (DCR)
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.
Measured: Up to approximately 12 months
Duration of Response (DOR)
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.
Measured: Up to approximately 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2025
- Study start27 Mar 2025
- Primary completion27 Mar 2027 (estimated)
- Study completion27 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Incyte Medical Monitor, Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06818812
- Sponsor's protocol ID
- INCB186748-101
- Other IDs
- 2024-519018-30-00
- Status last verified
- Aug 2026
- First submitted
- 5 Feb 2025
- Last updated
- 25 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Multicenter Study of INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
- ClinicalTrials.gov ID
- NCT06818812
- Acronym / sponsor ID
- INCB186748-101
- Conditions
- Solid Tumors
- Keywords
- INCB186748, KRASG12D Mutation, pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Incyte CorporationIndustry (pharma, biotech, devices)
- Study start
- 27 Mar 2025 (actual)
- Primary completion
- 27 Mar 2027 (estimated)
- Study completion
- 27 Mar 2027 (estimated)
- First posted
- 10 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part 1a: Dose Escalation monotherapy | Experimental | Drug: INCB186748INCB186748 at the protocol-defined dose strength based on cohort assignment. |
| Part 1b: Dose Expansion monotherapy | Experimental | Drug: INCB186748INCB186748 at the protocol-defined dose strength based on cohort assignment. |
| Part 1c: Pharmacodynamic cohort | Experimental | Drug: INCB186748INCB186748 at the protocol-defined dose strength based on cohort assignment. |
| Part 1d: Food-Effect | Experimental | Drug: INCB186748Evaluate food effect on drug exposure as defined in the protocol. |
| Part 2a: Dose Escalation combination | Experimental | Drug: INCB186748, Drug: Cetuximab, Drug: GEMNabP, Drug: mFOLFIRINOXINCB186748 in combination at the protocol-defined dose strength based on cohort assignment. |
| Part 2b: Dose Expansion combination | Experimental | Drug: INCB186748, Drug: Cetuximab, Drug: GEMNabP, Drug: mFOLFIRINOXINCB186748 in combination at the protocol-defined dose strength based on cohort assignment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- ≥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:
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INCB186748INCB186748 will be administered at protocol defined dose. | Drug | 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 |
| CetuximabCetuximab will be administered at protocol defined dose. | Drug | Part 2a: Dose Escalation combination, Part 2b: Dose Expansion combination |
| GEMNabPGEMNabP will be administered at protocol defined dose. | Drug | Part 2a: Dose Escalation combination, Part 2b: Dose Expansion combination |
| mFOLFIRINOXmFOLFIRINOX will be administered at protocol defined dose. | Drug | Part 2a: Dose Escalation combination, Part 2b: Dose Expansion combination |
Primary outcome
Number of participants with Dose Limiting Toxicities (DLTs)
Time frame: 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)
Time frame: 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
Time frame: Up to approximately 12 months and 60 days
Number of participants with TEAEs leading to dose modification or discontinuation.
4 secondary outcomes
INCB186748 pharmacokinetic (PK) in Plasma
Time frame: Up to approximately 12 months
Objective Response Rate (ORR)
Time frame: Up to approximately 12 months
Disease Control Response (DCR)
Time frame: Up to approximately 12 months
Duration of Response (DOR)
Time frame: Up to approximately 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2026.
- A Study to Evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D MutationLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Incyte Medical Monitor study director
Incyte Corporation
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INCB186748, Cetuximab and GEMNabP in people with Solid Tumors, run by Incyte Corporation at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Dose Limiting Toxicities (DLTs) (time frame: Up to 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.