Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
INCB161734 · 6 trials · 6 indications
Defined as the time from the date of randomization to the date of death due to any cause.
Defined as the time from the date of randomization to the date of the first documented progression as determined by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause.
Defined as complete response (CR) or partial response (PR) as determined by BICR per RECIST v1.1.
Defined as the maximum plasma concentration.
Defined as the area under the concentration-time curve from time zero to time of the last quantifiable concentration.
Defined as the area under concentration-time curve from time zero extrapolated to infinity.
Radioactivity in urine and feces was reported as the percentage of the administered radioactivity excreted.
To characterize the metabolic profile and identify circulating and excreted metabolites of INCB161734.
Defined as maximum observed plasma or serum concentration of INCB161734.
Defined as the area under the concentration-time curve up to the last measurable concentration of INCB161734.
Defined as the area under the concentration-time curve from 0 to infinity of INCB161734.
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug monotherapy and in combination with cetuximab and retifanlimab.
Number of participants with TEAEs leading to dose modification or discontinuation.
| Arm | Type | Description |
|---|---|---|
| INCB161734 plus chemotherapy | EXPERIMENTAL | INCB161734 at the protocol-defined dose with investigator's choice of chemotherapy (mFOLFIRINOX or GemNabP) in accordance with the protocol-defined requirements. |
| Placebo plus chemotherapy | EXPERIMENTAL | Placebo at the protocol-defined dose with investigator's choice of chemotherapy (mFOLFIRINOX or GemNabP) in accordance with the protocol-defined requirements. |
| Group 1: Severe renal impairment | EXPERIMENTAL | Participants with severe renal impairment will be enrolled in Group 1. |
| Group 2: End-stage renal disease (ESRD) | EXPERIMENTAL | Participants with end-stage renal disease will be enrolled in Group 2. |
| Cohort 1: Moderate hepatic impairment | EXPERIMENTAL | Participants with moderate hepatic impairment will be enrolled in Cohort 1. |
| Cohort 2: Severe hepatic impairment | EXPERIMENTAL | Participants with severe hepatic impairment will be enrolled in Cohort 2. |
| INCB161734 | EXPERIMENTAL | Participants will be administered orally a dose solution consisting of INCB161734 and radiolabeled INCB161734. |
| Cohort 1 | EXPERIMENTAL | INCB161734 and itraconazole will be administered at protocol defined doses. |
| Cohort 2 | EXPERIMENTAL | INCB161734 and rifampin will be administered at protocol defined doses. |
| Cohort 3 | EXPERIMENTAL | INCB161734 and esomeprazole will be administered at protocol defined doses. |
| Cohort 4 | EXPERIMENTAL | INCB161734 and famotidine will be administered at protocol defined doses. |
| Part 1a: Dose Escalation monotherapy | EXPERIMENTAL | INCB161734 at the protocol-defined dose strength based on cohort assignment. |
| Part 1b: Dose Expansion monotherapy | EXPERIMENTAL | INCB161734 at the protocol-defined dose strength based on cohort assignment. |
| Part 1c: Pharmacodynamic cohort | EXPERIMENTAL | INCB161734 at the protocol-defined dose strength based on cohort assignment. |
| Part 2a: Dose Escalation combination | EXPERIMENTAL | INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. |
| Part 2b: Dose Expansion combination | EXPERIMENTAL | INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. |
| Part 1d: Food-Effect | EXPERIMENTAL | Evaluate food effect on drug exposure as defined in the protocol. |
| Name | Type | Description |
|---|---|---|
| INCB161734 | DRUG | Oral; tablet |
| Placebo | DRUG | Oral; tablet |
| Investigator's choice of chemotherapy | DRUG | The investigator will select the chemotherapy in accordance with the protocol-defined requirements. The possible choices as defined by the protocol: |
| Itraconazole | DRUG | Oral; Tablet |
| Rifampin | DRUG | Oral; Tablet |
| Esomeprazole | DRUG | Oral; Tablet |
| Famotidine | DRUG | Oral; Tablet |
| Cetuximab | DRUG | Cetuximab will be administered at protocol defined dose. |
| Retifanlimab | DRUG | Retifanlimab will be administered at protocol defined dose. |
| GEMNabP | DRUG | GEMNabP will be administered at protocol defined dose. |
| mFOLFIRINOX | DRUG | mFOLFIRINOX will be administered at protocol defined dose. |
| FOLFOX | DRUG | FOLFOX will be administered at protocol defined dose. |
| FOLFIRI | DRUG | FOLFIRI will be administered at protocol defined dose. |
| INCA33890 | DRUG | INCA33890 will be administered at protocol defined dose. |
Inclusion Criteria: * Histologically or cytologically confirmed metastatic PDAC with a KRAS G12D mutation * No prior systemic treatment in the metastatic setting * ECOG Performance status 0-1 * Adequate organ function Exclusion Criteria: * Prior treatment with any KRAS inhibitor * Chronic or curr...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 2 | PHASE2 | Pembrolizumab, Gardasil 9 |
| Incyte Corporation | INCY | 1 | PHASE2 | Retifanlimab |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | Aldesleukin |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115 |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
INCB161734 is an investigational small molecule developed by Incyte Corporation. It is being studied in healthy participants, in people with hepatic or renal insufficiency, and in solid tumors, including KRAS G12D-mutated metastatic pancreatic ductal adenocarcinoma. It remains in clinical development and is not an approved therapy.
INCB161734 targets KRASG12D, a mutant form of the KRAS protein. By binding this specific mutant target, the small molecule is designed to act on tumors carrying the KRAS G12D alteration, which is the focus of its pancreatic ductal adenocarcinoma study.
Incyte Corporation develops INCB161734. Incyte is a biopharmaceutical company traded on Nasdaq under the ticker INCY. The company is the sponsor of the clinical program evaluating the drug across pharmacokinetic studies and a Phase 3 pancreatic cancer trial.
INCB161734 is in Phase 1 development for pharmacokinetic and safety studies, and a Phase 3 trial is recruiting in KRAS G12D-mutated metastatic pancreatic ductal adenocarcinoma. The drug is investigational and has not been approved by the FDA for any indication.
Trials include NCT07522073, a Phase 3 study of chemotherapy with or without INCB161734 in previously untreated KRAS G12D-mutated metastatic pancreatic ductal adenocarcinoma, plus Phase 1 studies NCT07854249 in renal impairment and hemodialysis, NCT07853040 in hepatic impairment, and NCT07814404, a mass balance study in healthy male participants.
INCB161734 is being evaluated in solid tumors, specifically KRAS G12D-mutated metastatic pancreatic ductal adenocarcinoma. The Phase 3 NCT07522073 trial compares chemotherapy with or without INCB161734 in previously untreated patients across sites in the United States, Europe, Asia, and Australia.