Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as INCB 024360
Epacadostat · 11 trials · 16 indications
ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.
ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.
ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination. Responses are based on investigator assessments per RECIST 1.1 without confirmation using all available scans.
Overall survival is defined as the time interval from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. If a patient has not had an event, OS will be censored at the date of last follow up.
Overall survival is defined as the time interval from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. If a patient has not had an event, OS will be censored at the date of last follow up.
Overall survival is defined as the time interval from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. If a patient has not had an event, OS will be censored at the date of last follow up.
ORR is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) based on blinded independent central review (BICR).
ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on blinded independent central review (BICR).
To determine the safety of fixed doses of DEC205mAb-NY-ESO-1 fusion protein with adjuvant poly-ICLC given as a vaccine in combination with INCB024360 300mg, number of Participants with Dose Limiting Toxicities is reported
Percentage of Participants with Progression Free Survival Using irRC Criteria for Phase II Patients are reported. irRC criteria disease progression is defined as at least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 weeks apart.
All patients enrolled in this study will be eligible for the analysis of toxicity. The toxicity rate will be estimated using a one-sided, 95%, exact binomial confidence interval (Clopper-Pearson).
The recommended phase 2 dose (RP2D) is defined as the dose level immediately below the maximally administered dose at which 0 or 1 of a cohort of 3 to 6 patients experienced a dose-limiting toxicity (DLT) during first 2 cycles.
Neoadjuvant Rectal Score (NAR Score) is calculated by following formula: NAR = (\[5pN \- 3(cT - pT) + 12\]2)/9.61 (with higher scores representing poorer prognosis), where cT=clinical tumor stage, pT=pathologic tumor stage, and pN=pathologic nodal stage.
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of epacadostat, pembrolizumab, or chemotherapy. Serious adverse event is defined as an event that meets 1 of the following criteria: is fatal or life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability, incapacity, or a substantial disruption of a person's ability to conduct normal life functions, constitutes a congenital anomaly or birth defect,is a medically important event that may jeopardize the participant or may require medical or surgical intervention to prevent 1 of the outcomes listed above.
A DLT was defined as the occurrence of any of the protocol-specified toxicities occurring up to and including Day 28 for the cohorts where mFOLFOX6 and nab-paclitaxel/gemcitabine are administered and Day 21 for all other chemotherapy regimens in Phase 1, except those with a clear alternative explanation (eg, disease progression) or transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination.
ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT \> 3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.
A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT \> 3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.
ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR per RECIST v 1.1 was defined as At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. Data is reported as per dose received by the participants with a particular cancer type. CR per Cheson criteria was defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR per Cheson criteria was defined as at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses.
PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 or death due to any cause, whichever occurs first.
OS rate is defined as the proportion of participants alive 9 months after the start of treatment.
| Arm | Type | Description |
|---|---|---|
| Pembrolizumab 200 mg + Epacadostat 100 mg BID | EXPERIMENTAL | Pembrolizumab + epacadostat |
| Pembrolizumab 200 mg + placebo BID | ACTIVE_COMPARATOR | Pembrolizumab + placebo |
| Pembrolizumab + Epacadostat | EXPERIMENTAL | - |
| SoC (Sunitinib or Pazopanib) | ACTIVE_COMPARATOR | Standard of care (SoC) (sunitinib or pazopanib monotherapy). |
| Pembrolizumab | EXPERIMENTAL | - |
| EXTREME | ACTIVE_COMPARATOR | EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. |
| Regimen A: Retifanlimab+RT+bevacizumab | EXPERIMENTAL | * Retifanlimab will be given intravenously over the course of 30 to 60 minutes at a dose of 500 mg on Day 1 of each 28-day cycle. * Bevacizumab will be given intravenously at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle. * Ten fractions of radiation therapy will be given at a dose of 3.5 Gy per fraction * Retifanlimab and bevacizumab will be started approximately two weeks before the first day of radiation therapy * Treatment may continue for up to two years. |
| Regimen B: Retifanlimab+RT+bevacizumab+epacadostat | EXPERIMENTAL | * Retifanlimab will be given intravenously over the course of 30 to 60 minutes at a dose of 500 mg on Day 1 of each 28-day cycle. * Bevacizumab will be given intravenously at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle. * Ten fractions of radiation therapy will be given at a dose of 3.5 Gy per fraction * Retifanlimab and bevacizumab will be started approximately two weeks before the first day of radiation therapy * Epacadostat will be administered orally at 400 mg BID. * Treatment may continue for up to two years. |
| Pembrolizumab + Chemotherapy + Epacadostat | EXPERIMENTAL | Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). |
| Pembrolizumab + Chemotherapy + Placebo | EXPERIMENTAL | Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). |
| Pembrolizumab + Placebo | ACTIVE_COMPARATOR | Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05. |
| Arm I (CDX-1401, poly ICLC) | EXPERIMENTAL | Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC as in Phase I. |
| Arm II (CDX-1401, poly ICLC, IDO1 inhibitor INCB024360) | EXPERIMENTAL | Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, and IDO1 inhibitor INCB024360 as in Phase I. |
| Dose Escalation Cohort (Phase I): Epacadostat + SCRT + Chemotherapy + Surgery | EXPERIMENTAL | * Epacadostat at the designated dose level starting on the 1st day of radiation therapy and continuing throughout chemotherapy until the day of surgery. * Standard of care preoperative therapy will consist of a total of approximately 20-24 weeks of short-course pelvic radiation and chemotherapy: * Cycle 0 Days 1-7(Week 1): Short-course pelvic radiation therapy (SCRT), 5 fractions over 1 week * Cycle 0 Days 8-21 or 8-28 (Weeks 2-4): Treatment break for 2 to 3 weeks; for patients enrolled at Washington University and Dana Farber only, tumor biopsy will be obtained between the end of RT and prior to chemotherapy (target Days 14-28) * Cycles 1-6: (6) 21-day cycles of CAPOX for a total of 18 weeks. CAPOX is typically capecitabine at 1000 mg/m\^2 PO BID (days 1-14 of each cycle) and oxaliplatin 130 mg/m\^2 IV Q3W. * Surgery will follow approximately 4 to 6 weeks after completion of CAPOX |
| Phase II Treatment Cohort: Epacadostat + SCRT + Chemotherapy + Surgery | EXPERIMENTAL | * Epacadostat 400 mg BID 1st day of radiation therapy and continuing for \~28 days, until biopsy (with the exception of patients enrolling to dose expansion and starting on epacadostat with neoadjuvant chemotherapy prior to approval of post-sIRB A2) * Preoperative therapy approximately 20-24 weeks of chemoradiation: * Week 1: SCRT, typically 5 Gy x 5 fractions over 1 week, with epacadostat 400 mg BID starting on D1 of SCRT * Weeks 2-4: Epacadostat monotherapy 400 mg BID \& continued for a minimum of 21 days, until the day prior to chemotherapy * For patients enrolled at Washington University and Dana Farber Cancer Institute ONLY, tumor biopsy between the end of RT and prior to initiation of chemotherapy. Tumor biopsy target of between Days 15-28 * Weeks 3-6: 4-5 weeks after completion of SCRT \& after completion of approximately 21-35 days of epacadostat, SOC neoadjuvant chemotherapy of CAPOX or FOLFOX will be initiated * Surgery will occur approximately 4-6 weeks after chemotherapy |
| Phase II Biomarker Cohort: SCRT + Chemotherapy + Surgery | ACTIVE_COMPARATOR | Washington University and Dana Farber only: Patients enrolled to this cohort will not receive epacadostat. Patients will undergo standard of care preoperative therapy consisting of approximately 20 to 24 weeks of chemoradiation. All treatment will be administered in this cohort as per institutional standard. The expected schedule for these patients will consist of 1 week of short-course pelvic radiation therapy, followed by a treatment break, followed by neoadjuvant chemotherapy. Approximately 4 to 6 weeks after completion of neoadjuvant chemotherapy, patients may undergo surgery. Tumor biopsy may occur at screening and after completion of RT, prior to starting neoadjuvant chemotherapy. |
| Treatment Group A | EXPERIMENTAL | Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil) |
| Treatment Group B | EXPERIMENTAL | Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel |
| Treatment Group C | EXPERIMENTAL | Epacadostat + pembrolizumab + carboplatin and paclitaxel |
| Treatment Group D | EXPERIMENTAL | Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent |
| Treatment Group E | EXPERIMENTAL | Epacadostat + pembrolizumab + cyclophosphamide |
| Treatment Group F | EXPERIMENTAL | Epacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent |
| Treatment Group G | EXPERIMENTAL | Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil |
| Phase 1 Part 1 Epacadostat 25mg BID +Nivolumab | EXPERIMENTAL | Epacadostat 25mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W |
| Phase 1 Part 1 Epacadostat 50mg BID +Nivolumab | EXPERIMENTAL | Epacadostat 50mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W |
| Phase 1 Part 1 Epacadostat 100mg BID +Nivolumab | EXPERIMENTAL | Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W. |
| Phase 1 Part 1 Epacadostat 300mg BID +Nivolumab | EXPERIMENTAL | Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W. |
| Phase 1 Part 2 Epacadostat 100mg BID +Nivolumab +5-FU/Platinum | EXPERIMENTAL | Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 360mg Q3W and 5-FU/Platinum( Carboplatin or Cisplatin+5-Fluorouracil) administered intravenously (IV). |
| Phase 1 Part 2 Epacadostat 100mg BID +Pemetrexed/Platinum | EXPERIMENTAL | Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 360 mg Q3W and Pemetrexed/Platinum (Carboplatin orCisplatin+Pemetrexed) administered intravenously (IV). |
| Phase 1 Part 2 Epacadostat 100mg BID +Paclitaxel/Platinum | EXPERIMENTAL | Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 360 mg Q3W and Paclitaxel/Platinum(Carboplatin+Cisplatin+Paclitaxel)administered intravenously (IV). |
| Phase 2 Epacadostat 100mg BID + Nivolumab | EXPERIMENTAL | Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 240mg Q2W or 480 mg Q4W based on tumor type administered intravenously (IV). |
| Phase 2 Epacadostat 300mg BID + Nivolumab | EXPERIMENTAL | Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 240mg Q2W administered intravenously (IV). |
| Name | Type | Description |
|---|---|---|
| Pembrolizumab | DRUG | Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. |
| Epacadostat | DRUG | Epacadostat administered orally twice daily. |
| Placebo | DRUG | Matching placebo administered orally twice daily. |
| Sunitinib | DRUG | Sunitinib 50 mg administered orally once daily; 4 weeks on, 2 weeks off for 6-wk cycle. |
| Pazopanib | DRUG | Pazopanib 800 mg administered orally once daily. |
| Cetuximab | DRUG | Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. |
| Cisplatin | DRUG | Cisplatin administered intravenously every 3 weeks for \</= 6 cycles. |
| Carboplatin | DRUG | Carboplatin administered intravenously every 3 weeks for \</= 6 cycles. |
| 5-Fluorouracil | DRUG | 5-Fluorouracil administered intravenously every 3 weeks for \</= 6 cycles. |
| Bevacizumab | DRUG | -The first infusion will be over the course of 90 minutes; if tolerated, the second infusion will be over the course of 60 minutes; if tolerated, all subsequent infusions will be over 30 minutes |
| Radiation therapy | RADIATION | -The gross tumor maximum diameter (to be irradiated) to be \</= 6 cm in the first 6 patients. If more than 1 target is irradiated, then the sum of all the target maximum diameters should be \</= 6 cm. No more than 3 separate targets for RT is allowed. |
| Retifanlimab | DRUG | -Will be supplied by Incyte |
| Platinum-based chemotherapy | DRUG | Investigator selected one of the following regimens: pemetrexed + cisplatin, pemetrexed + carboplatin, or paclitaxel + carboplatin, depending on histology. |
| DEC-205/NY-ESO-1 Fusion Protein CDX-1401 | BIOLOGICAL | Given via intracutaneous injection |
| Laboratory Biomarker Analysis | OTHER | Correlative studies |
| Pharmacological Study | OTHER | Correlative studies |
| Poly ICLC | DRUG | Given SC |
| Short-course radiation therapy | RADIATION | Short-course pelvic radiation therapy, 5 Gy x 5 fractions over 1 week |
| CAPOX chemotherapy | DRUG | Standard of care |
| FOLFOX chemotherapy | DRUG | Standard of care |
| Oxaliplatin | DRUG | Oxaliplatin |
| Leucovorin | DRUG | Leucovorin |
| Gemcitabine | DRUG | Gemcitabine |
| nab-Paclitaxel | DRUG | nab-Paclitaxel |
| Paclitaxel | DRUG | Paclitaxel |
| Pemetrexed | DRUG | Pemetrexed |
| Cyclophosphamide | DRUG | Cyclophosphamide |
| Investigator's choice of platinum agent | DRUG | Investigator's choice of platinum agent: carboplatin or cisplatin |
| Nivolumab | DRUG | specified dose and dosing schedule |
| Chemotherapy | DRUG | Specified dose on specified days |
Inclusion Criteria: * Histologically-confirmed diagnosis of urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, that is transitional cell, or mixed transitional/non-transitional (predominantly transitional) cell type. * Progression or recurrence of urothelial carcinoma following ...
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Epacadostat is an investigational small molecule being studied in oncology across several tumor types, including B-cell malignancies, glioma, head and neck cancer, lung cancer, rectal cancer, and fallopian tube carcinoma. It is not an approved therapy and remains in clinical development.
Epacadostat targets IDO1, an enzyme also known as indoleamine 2,3-dioxygenase 1. It acts as an IDO1 inhibitor. By inhibiting this target, the drug is designed to modulate tryptophan metabolism in the tumor microenvironment, a pathway studied for its role in cancer immune evasion.
Epacadostat is developed by Incyte Corporation, a biopharmaceutical company traded on Nasdaq under the ticker INCY. Incyte is the sponsor of the clinical programs evaluating the drug, including studies combining it with other agents such as pembrolizumab and retifanlimab.
Epacadostat is in Phase 1 development according to its current development stage, though individual studies have been conducted at Phase 2 and Phase 3. It is an investigational agent and has not been approved by the FDA for any indication.
Epacadostat has been evaluated in trials including NCT03532295, a Phase 2 study of retifanlimab and epacadostat with radiation and bevacizumab in recurrent gliomas, and NCT03516708, a Phase 1 study in locally advanced rectal cancer. Phase 3 studies NCT03374488 and NCT03361865 tested it with pembrolizumab in urothelial carcinoma.
Yes, INCB024360 is an alternative name for epacadostat. The two names refer to the same investigational IDO1 inhibitor developed by Incyte Corporation, and both appear in the clinical literature and trial records for the same compound.