INCAGN01876 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies

• INCAGN01876 (Drug): In Phase 1 subjects will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose and schedule according to cohort and treatment group enrollment. In Phase 2, subjects will be administered IV study drug at the recommended dose from Phase 1.
• Epacadostat (Drug), also known as INCB024360: Epacadostat will be self-administered orally at the protocol-defined dose.
• Pembrolizumab (Drug), also known as Keytruda®: Pembrolizumab will be administered IV at the protocol-defined dose.

Primary outcomes

• Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] [Screening through 60 days after end of treatment, up to approximately 18 months]: A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment.
• Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months]: Defined as the percentage of participants having a CR or PR based on investigator assessment per RECIST v1.1.
• Phase 2: Complete Response Rate (CRR) Based on RECIST v1.1 [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months]: Defined as the percentage of checkpoint inhibitor-naive melanoma participants who have a CR based on investigator assessment per RECIST v1.1

Secondary outcomes

• Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months.]: Defined as the percentage of participants having CR, PR, or stable disease (SD) based on investigator assessment per RECIST v1.1.
• Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months]: Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause.
• Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months]: Defined as time from first report of SD or better until disease progression or death from any cause.
• Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months]: Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause.
• Phase 1 & Phase 2: Overall Survival [At 1 year and 2 years.]: Defined as the time from the start of combination therapy until death due to any cause.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
* Phase 1: Subjects with advanced or metastatic solid tumors.
* Phase 1: Subjects who have disease progression after treatment with available therapies.
* Phase 2: Subjects with advanced or metastatic melanoma, RCC, and urothelial carcinoma.
* Presence of measurable disease based on RECIST v1.1.
* Eastern Cooperative Oncology Group performance status of 0 or 1.

Exclusion Criteria:

* Laboratory and medical history parameters not within the Protocol-defined range
* Prior treatment with any tumor necrosis factor super family agonist.
* Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
* Has not recovered to ≤ Grade 1 from toxic effects of prior therapy.
* Active autoimmune disease.
* Known active central nervous system metastases and/or carcinomatous meningitis.
* Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
* Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
* Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).

Participant flow

Outcome results

• Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] (Primary), Count of participants, Participants: INCAGN01876 + Pembrolizumab + Epacadostat 10
• Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST (Primary), Count of participants, Participants: INCAGN01876 + Pembrolizumab + Epacadostat 3
• Phase 2: Complete Response Rate (CRR) Based on RECIST v1.1 (Primary)
• Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST (Secondary), Count of participants, Participants: INCAGN01876 + Pembrolizumab + Epacadostat 7
• Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST (Secondary), Median, days: INCAGN01876 + Pembrolizumab + Epacadostat NA (273 to NA)
• Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST (Secondary), Median, days: INCAGN01876 + Pembrolizumab + Epacadostat NA (525 to NA)
• Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST (Secondary), Median, months: INCAGN01876 + Pembrolizumab + Epacadostat 17.36 (2.05 to NA)
• Phase 1 & Phase 2: Overall Survival (Secondary), Median, months: INCAGN01876 + Pembrolizumab + Epacadostat 25.59 (16.76 to NA)

Adverse events

Time frame: up to 18 months

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2017-08-24)
• Statistical Analysis Plan (PDF, 2018-06-01)

• John N. Janik, MD, Study director, Incyte Corporation