A Phase 1/2 Study of the Safety, Tolerability, and Efficacy of Epacadostat Administered in Combination With Nivolumab in Select Advanced Cancers (ECHO-204)
Overview
- Phase
- Phase 1
- Intervention
- Nivolumab
- Conditions
- B-cell Malignancies
- Sponsor
- Incyte Corporation
- Enrollment
- 307
- Locations
- 23
- Primary Endpoint
- Phase 2: Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
This is a Phase 1/2, open label study. Phase 1 consists of 2 parts. Part 1 is a dose-escalation assessment of the safety and tolerability of epacadostat administered with nivolumab in subjects with select advanced solid tumors and lymphomas. Part 2 will evaluate the safety and tolerability of epacadostat in combination with nivolumab and chemotherapy in subjects with squamous cell carcinoma of head and neck (SCCHN) and non-small cell lung cancer (NSCLC).
Phase 2 will include expansion cohorts in 7 tumor types, including melanoma, NSCLC, SCCHN, colorectal cancer, ovarian cancer, glioblastoma and diffuse large B-cell lymphoma (DLBCL).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female subjects, age 18 years or older
- •Subjects with histologically or cytologically confirmed NSCLC, MEL (including I/O relapsed MEL or I/O refractory MEL), CRC, SCCHN, ovarian cancer, recurrent B cell NHL or HL, or glioblastoma
- •Presence of measurable disease by RECIST v1.1 for solid tumors or Cheson criteria for B cell NHL (including DLBCL) or HL. For subjects with glioblastoma, presence of measurable disease is not required.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- •Fresh baseline tumor biopsies (defined as a biopsy specimen taken since completion of the most recent prior chemotherapy regimen) are required for all cohorts except glioblastoma
Exclusion Criteria
- •Laboratory and medical history parameters not within Protocol-defined range
- •Currently pregnant or breastfeeding
- •Subjects who have received prior immune checkpoint inhibitors or an IDO inhibitor (except select Phase 2 cohorts evaluating I/O relapsed or I/O refractory MEL). Subjects who have received experimental vaccines or other immune therapies should be discussed with the medical monitor to confirm eligibility
- •Untreated central nervous system (CNS) metastases or CNS metastases that have progressed
- •Subjects with any active or inactive autoimmune process
- •Evidence of interstitial lung disease or active, noninfectious pneumonitis
- •Subjects with any active or inactive autoimmune process
- •Ocular MEL
Arms & Interventions
Phase 1 Part 1 Epacadostat 25mg BID +Nivolumab
Epacadostat 25mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W
Intervention: Nivolumab
Phase 1 Part 1 Epacadostat 25mg BID +Nivolumab
Epacadostat 25mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W
Intervention: Epacadostat
Phase 1 Part 1 Epacadostat 50mg BID +Nivolumab
Epacadostat 50mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W
Intervention: Nivolumab
Phase 1 Part 1 Epacadostat 50mg BID +Nivolumab
Epacadostat 50mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W
Intervention: Epacadostat
Phase 1 Part 1 Epacadostat 100mg BID +Nivolumab
Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W.
Intervention: Nivolumab
Phase 1 Part 1 Epacadostat 100mg BID +Nivolumab
Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W.
Intervention: Epacadostat
Phase 1 Part 1 Epacadostat 300mg BID +Nivolumab
Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W.
Intervention: Nivolumab
Phase 1 Part 1 Epacadostat 300mg BID +Nivolumab
Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W.
Intervention: Epacadostat
Phase 1 Part 2 Epacadostat 100mg BID +Nivolumab +5-FU/Platinum
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).
Intervention: Nivolumab
Phase 1 Part 2 Epacadostat 100mg BID +Nivolumab +5-FU/Platinum
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).
Intervention: Epacadostat
Phase 1 Part 2 Epacadostat 100mg BID +Nivolumab +5-FU/Platinum
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).
Intervention: Chemotherapy
Phase 1 Part 2 Epacadostat 100mg BID +Pemetrexed/Platinum
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).
Intervention: Epacadostat
Phase 1 Part 2 Epacadostat 100mg BID +Pemetrexed/Platinum
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).
Intervention: Chemotherapy
Phase 1 Part 2 Epacadostat 100mg BID +Paclitaxel/Platinum
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).
Intervention: Epacadostat
Phase 1 Part 2 Epacadostat 100mg BID +Paclitaxel/Platinum
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).
Intervention: Chemotherapy
Phase 2 Epacadostat 100mg BID + Nivolumab
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).
Intervention: Nivolumab
Phase 2 Epacadostat 100mg BID + Nivolumab
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).
Intervention: Epacadostat
Phase 2 Epacadostat 300mg BID + Nivolumab
Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 240mg Q2W administered intravenously (IV).
Intervention: Nivolumab
Phase 2 Epacadostat 300mg BID + Nivolumab
Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 240mg Q2W administered intravenously (IV).
Intervention: Epacadostat
Outcomes
Primary Outcomes
Phase 2: Progression Free Survival (PFS)
Time Frame: From first dose up end of the study (up to approximately 6 years)
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.
Phase 1, Part 2: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Day 42
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.
Phase 1, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Day 42
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.
Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)
Time Frame: up to approximately 39 months
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.
Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL
Time Frame: From first dose up end of the study (up to approximately 6 years)
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.
Phase 2: Overall Survival (OS) Rate of Proportion With Glioblastoma
Time Frame: Month 9
OS rate is defined as the proportion of participants alive 9 months after the start of treatment.
Secondary Outcomes
- Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD)(From first dose up end of the study (up to approximately 6 years))
- Phase 1, Part 2: Duration of Response (DOR) for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC(From first dose up end of the study (up to approximately 6 years))
- Phase 1, Part 2: ORR Per RECIST v1.1 and for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC(From first dose up end of the study (up to approximately 6 years))
- Phase 1, Part 1: ORR Per RECIST v1.1 for Participants With Solid Tumors; Per Cheson Criteria for Participants With B-cell NHL; and Per RANO and mRANO Criteria for Participants With GBM(From first dose up end of the study (up to approximately 6 years))
- Phase 1, Part 2: PFS for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC(From first dose up end of the study (up to approximately 6 years))
- Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs(up to approximately 35 months)
- Phase 2: Duration of Response(From first dose up end of the study (up to approximately 6 years))