Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Epacadostat · 3 trials · 4 indications
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.
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.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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 |
| Name | Type | Description |
|---|---|---|
| Epacadostat | DRUG | -All BID doses will be taken in the morning and evening, approximately 12 hours apart |
| 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 |
| 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 |
| Pembrolizumab | DRUG | Pembrolizumab |
| Oxaliplatin | DRUG | Oxaliplatin |
| Leucovorin | DRUG | Leucovorin |
| 5-Fluorouracil | DRUG | 5-Fluorouracil |
| Gemcitabine | DRUG | Gemcitabine |
| nab-Paclitaxel | DRUG | nab-Paclitaxel |
| Carboplatin | DRUG | Carboplatin |
| Paclitaxel | DRUG | Paclitaxel |
| Pemetrexed | DRUG | Pemetrexed |
| Cyclophosphamide | DRUG | Cyclophosphamide |
| Cisplatin | DRUG | Cisplatin |
| Investigator's choice of platinum agent | DRUG | Investigator's choice of platinum agent: carboplatin or cisplatin |
Inclusion Criteria: * Recurrent WHO grade 4 glioblastoma or gliosarcoma, including molecular features of glioblastoma and WHO grade 4 astrocytoma or WHO grade high grade glioma. * Other GBM variants and "secondary GBM" are allowed. All grade 4 gliomas that have relapsed more than once may be includ...
Epacadostat is an investigational small molecule being studied for use in oncology. It is being evaluated in clinical trials for solid tumors, glioma, and rectal cancer. In these settings, it is tested in combination with other therapies, such as pembrolizumab and chemotherapy, or with radiation and bevacizumab.
Epacadostat targets the enzyme indoleamine 2,3-dioxygenase (IDO), which is part of the -stat enzyme class. By inhibiting IDO, it is designed to modulate the tumor microenvironment, potentially enhancing anti-tumor immune responses when combined with other treatments.
Epacadostat is being developed by Incyte Corporation, a biopharmaceutical company traded on the NASDAQ under the ticker symbol INCY. Incyte is conducting clinical trials to evaluate the drug's safety and efficacy in various cancer indications.
Epacadostat is in Phase 2 clinical development. It is not FDA approved and remains investigational. The drug is being studied in combination with other agents in trials for solid tumors, rectal cancer, and glioma, with one Phase 2 trial completed and others in earlier phases.
Epacadostat is being studied in several clinical trials. NCT03085914 is a completed Phase 1 trial combining epacadostat with pembrolizumab and chemotherapy in advanced solid tumors. NCT03516708 is a recruiting Phase 1 trial adding epacadostat to preoperative chemoradiation in rectal cancer. NCT03532295 is a completed Phase 2 trial with retifanlimab, radiation, and bevacizumab in recurrent gliomas.
Yes, Epacadostat is also known as INCB024360. This alternative name appears in clinical trial records, such as NCT03516708, which lists the drug as Epacadostat (INCB024360). Researchers and investors may encounter either name when reviewing study documentation.