Bladder Cancer, Endometrial Cancer, Gastric Cancer, Head and Neck Cancer, Hepatocellular Carcinoma (HCC), Lung Cancer, Lymphoma, Melanoma, Microsatellite-instability (MSI) High Colorectal Cancer (CRC), Ovarian Cancer, Renal Cell Carcinoma (RCC), Solid Tumors, Triple Negative Breast Cancer (TNBC), UC (Urothelial Cancer)
Conditions
Brief summary
The purpose of this study was to assess the safety, tolerability, and efficacy when combining MK-3475 and INCB024360 in participants with certain cancers. This study was conducted in 2 phases, Phase 1 and Phase 2.
Interventions
DRUGMK-3475
IV infusion
DRUGINCB024360
Oral daily dosing
Sponsors
Merck Sharp & Dohme LLC
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with histologically or cytologically non-small cell lung cancer (NSCLC), melanoma, transitional cell carcinoma of the genitourinary (GU) tract, renal cell cancer, triple negative breast cancer, adenocarcinoma of the endometrium or squamous cell carcinoma of the head and neck (Phase 1). * Subjects with histologically confirmed melanoma, NSCLC, transitional cell carcinoma of the GU tract, TNBC, SCCHN, ovarian cancer, MSI high colorectal cancer (CRC), RCC, gastric cancer, HCC and DLBCL (Phase 2). * Life expectancy \> 12 weeks. * Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1. * Presence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Lugano Classification for subjects with DLBCL. * Laboratory and medical history parameters within protocol-defined range. * For Phase 1: Subjects who have advanced or metastatic disease as noted above that have received at least one prior therapy or have advanced or metastatic disease for which no curative treatment is available may be enrolled. * For Phase 2 expansion cohorts: Subjects with NSCLC, melanoma (checkpoint inhibitor naïve, primary refractory melanoma, relapsed melanoma), transitional cell carcinoma of the GU tract, SCCHN, ovarian cancer, MSI high CRC, RCC, DLBCL, TNBC, gastric cancer, and HCC. * Phase 2 expansion: NSCLC * Subjects who have received at least 1 prior platinum-based therapy. Subjects who have a non-platinum-based regimen may be enrolled with medical monitor approval. * Tumors with epidermal growth factor receptor mutation positive or anaplastic lymphoma kinase fusion oncogene positive treated with a tyrosine kinase inhibitor are permitted; however, subjects should have progressed on or be intolerant to the targeted therapy. * Subjects must not have received immunotherapy with programmed death receptor-1 (PD-1) or cytotoxic T-lymphocyte antigen (CTLA-4) targeted therapy. * Phase 2 expansion: Melanoma * Documentation of V600E-activating BRAF mutation status. * Prior systemic therapy requirements. * Melanoma immune checkpoint-naïve: Subjects must not have received immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. Exception: Prior anti-CTLA-4 in the adjuvant setting would be permitted. * Primary refractory melanoma: Subjects must have received prior treatment with anti-PD-1 or anti-PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and have progressive disease as their best response to treatment that is confirmed 4 weeks later. * Relapsed melanoma: Subjects must have received prior anti-PD-1 or anti-PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and achieved partial response ore complete response but later have confirmed progressive disease. * Subjects enrolling in the primary refractory or relapsed melanoma must be willing to undergo mandatory pretreatment and on-treatment biopsies. * Ocular melanoma is excluded. * Phase 2 expansion: Transitional cell carcinoma of the GU tract * Metastatic or locally advanced and not amenable to curative therapy with disease progression on or after platinum-based chemotherapy or alternative therapy if platinum-based therapy is not appropriate. * Prior PD-1 or CTLA-4 targeted therapies are excluded * Phase 2 expansion: SCCHN * Histologically confirmed metastatic or recurrent squamous cell carcinoma not amenable to local therapy with curative intent (surgery or radiation with or without chemotherapy). Carcinoma of the nasopharynx, salivary gland, or \* \*Subjects must have received at least 1 prior systemic chemotherapy regimen that must have included a platinum-based therapy. * Prior PD-1 or CTLA-4 targeted therapies are excluded. * Phase 2 expansion: Ovarian cancer * Subjects with FIGO Stage Ic, Stage II, Stage III, Stage IV, recurrent, or persistent (unresectable) histologically confirmed epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube carcinoma. * Subjects must have received a platinum-taxane-based regimen as first-line therapy. * Prior PD-1 or CTLA-4 targeted therapies are excluded. * Borderline, low-malignant-potential epithelial carcinoma per histopathology is excluded. * Phase 2 expansion: Relapsed or refractory DLBCL * Prior allogeneic stem-cell transplantation is excluded. * Must have received \> or = 1 prior treatment regimen. * Not a candidate for curative therapy or hematopoietic stem-cell transplantation (either due to disease burden, fitness, or preference). * Prior PD-1 or CTLA-4 targeted therapies are excluded. * Phase 2 expansion: TNBC * Histologically confirmed breast adenocarcinoma that is unresectable loco regional, or metastatic * Pathologically confirmed as triple negative, source documented, defined as both of the following: * Estrogen receptor (ER) and progesterone receptor (PgR) negative. * Human epidermal growth factor receptor 2 (HER2) negative as per American Society of Clinical Oncology/College of American Pathologists guidelines. * Subject must have received at least 1 prior systemic regimen for advanced or metastatic disease * Prior PD-1 or CTLA-4 targeted therapies are excluded. * Phase 2 expansion: RCC * Subjects with histological or cytological confirmation of clear cell RCC. * Not curable by surgery. * Subjects must have received prior antiangiogenic therapy. * Subjects must not have received prior immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. * Phase 2 expansion: MSI high CRC * Subjects with histological confirmation of locally advanced unresectable or metastatic MSI high CRC. * MSI status is, respectively, determined by examining CRC tumor. * Subjects may have received no more than 2 lines of prior therapy for advanced disease. * Phase 2 expansion: Gastric Cancer * Must have histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma. * Must have progression on or after therapy containing platinum/fluoropyrimidine or refused standard therapy. * Subjects may have received no more than 2 lines of prior therapy for advanced disease. * Prior PD-1 or CTLA-4 targeted therapies are excluded. * Phase 2 expansion: HCC * Must have histologically or cytologically confirmed diagnosis of HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible). * Barcelona Clinic Liver Cancer (BCLC) Stage C disease (Llovet et al 1999), or BCLC Stage B disease. * Subjects may have received no more than 2 lines of prior therapy for the advanced disease * Must have progressed on, refused, or were intolerant of sorafenib. * The following are excluded: Subjects with liver transplants, clear invasion of the bile duct or main portal branch(es), or hepatorenal syndrome, or subjects who have required esophageal variceal ablation within 28 days of starting study treatment. * Prior PD-1 or CTLA-4 targeted therapies are excluded. * Tumor biopsies are required. If a subject has inaccessible lesions, such as in ovarian cancer, HCC, or gastric cancer, or highly vascular lesions, such as RCC, enrollment may be considered with medical monitor approval, and archived tissue may be acceptable. * Females of child-bearing potential and males who use adequate birth control through 120 days post dose.
Exclusion criteria
* Subjects who participated in any other study in which receipt of an investigational study drug or device occurred within 2 weeks or 5 half-lives (whichever is longer) prior to first dose. * Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Exception: Prior anti-CTLA-4 in the adjuvant setting for subjects with melanoma would be permitted. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable. * Has an active autoimmune disease. * Has evidence of noninfectious pneumonitis that required steroids or current pneumonitis. * Live vaccine use within 30 days of first dose of study medication. * Monoamine oxidase inhibitors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | Approximately 54 months | An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. A TEAE is any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful (i.e. defined as an event that jeopardizes the participant or requires potential medical or surgical intervention to prevent 1 of the outcomes listed above) or requires inpatient hospitalization or prolongation of existing hospitalization. |
| Phase 2: Objective Response Rate (ORR) | Approximately 54 months | ORR was percentage of participants with best overall response \[complete response (CR) or partial response (PR)\], per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Duration of Disease Control | Up to 54 months | The duration of disease control is the time from the treatment start date to the first objective response of PD (by irRECIST v1.1 or Lugano Classification), death, or last tumor assessment date (if PD/death not present), for subjects with best overall response of SD or better. |
| Phase 2: Overall Survival (OS) | Up to 54 months | Overall survival is determined from the date of first dose until death due to any cause. |
| Phase 2: Duration of Response (DOR) | Up to 54 months | Duration of response is the time from the first overall response contributing to an objective response (complete or partial response) for DLBCL to the date of death or the date of first overall response of progressive diseasemeasured (by irRECIST for solid tumors or the Lugano Classification, whichever is earliest. |
| Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | Up to 54 months | — |
| Phase 2: Ordinal Categorical Response Score | Up to 54 months | Ordinal categorical response score, determined by radiographic disease assessments per irRECIST v1.1. The 5-category ordinal response endpoint is determined at a given timepoint by classifying response into one of the following groups: 1 = Complete response per irRECIST v1.1 2 = Very good response, defined as \> 60% tumor reduction 3 = Minor response, defined as \> 30% to ≤ 60% tumor reduction 4 = Stable disease per irRECIST v1.1 5 = Progressive disease per irRECIST v1.1 |
| Phase 2: Progression Free Survival (PFS) | Up to 54 months | Progression-free survival is defined as number of days from the first day of taking study drug to the earlier of death or disease progression by irRECIST v1.1 for select solid tumors and modified Lugano Classification for DLBCL. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 22 investigative sites in the United States from 17July 2014 to 06 November 2020.
Pre-assignment details
Prior to 17May18 study amended/discontinued, 444 participants were enrolled. Survival follow up and monotherapy option after discontinuation of combination were removed so anyone in survival follow up were discontinued the study and were assigned to study terminated by sponsor because completed was not an option in the database for those in survival follow up. 1 patient on combo treatment did not move to the monotherapy so they were also assigned to this reason for discontinuing.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Epacadostat 25 mg BID Epacadostat 25 mg tablet orally twice daily (BID) starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | 4 |
| Phase 1: Epacadostat 50 mg BID Epacadostat 50 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | 20 |
| Phase 1: Epacadostat 100 mg BID Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | 18 |
| Phase 1: Epacadostat 300 mg BID Epacadostat 300 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | 20 |
| Phase 2: Epacadostat 100 mg BID Epacadostat 100 mg tablet orally BID in combination with pembrolizumab 200 mg intravenously every 3 weeks (Q3W). | 382 |
| Total | 444 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 13 | 12 | 12 | 205 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 2 | 11 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 3 |
| Overall Study | Study terminated by Sponsor | 2 | 7 | 6 | 4 | 128 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 2 | 33 |
Baseline characteristics
| Characteristic | Phase 1: Epacadostat 50 mg BID | Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 100 mg BID | Phase 1: Epacadostat 300 mg BID | Phase 2: Epacadostat 100 mg BID | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 12.97 | 48.8 years STANDARD_DEVIATION 18.01 | 63.2 years STANDARD_DEVIATION 13.67 | 59.2 years STANDARD_DEVIATION 13.06 | 62.7 years STANDARD_DEVIATION 11.6 | 62.3 years STANDARD_DEVIATION 11.92 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 15 Participants | 17 Participants |
| Race/Ethnicity, Customized Black/African-American | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 19 Participants | 22 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 16 Participants | 18 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 20 Participants | 4 Participants | 17 Participants | 19 Participants | 353 Participants | 413 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants | 9 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 10 Participants | 10 Participants |
| Race/Ethnicity, Customized White/Caucasian | 20 Participants | 1 Participants | 18 Participants | 17 Participants | 337 Participants | 393 Participants |
| Sex: Female, Male Female | 9 Participants | 3 Participants | 6 Participants | 9 Participants | 181 Participants | 208 Participants |
| Sex: Female, Male Male | 11 Participants | 1 Participants | 12 Participants | 11 Participants | 201 Participants | 236 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 13 / 20 | 12 / 18 | 14 / 20 | 209 / 382 | 250 / 444 |
| other Total, other adverse events | 4 / 4 | 18 / 20 | 17 / 18 | 20 / 20 | 375 / 382 | 434 / 444 |
| serious Total, serious adverse events | 0 / 4 | 8 / 20 | 9 / 18 | 9 / 20 | 195 / 382 | 221 / 444 |
Outcome results
Primary
Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events
An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. A TEAE is any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful (i.e. defined as an event that jeopardizes the participant or requires potential medical or surgical intervention to prevent 1 of the outcomes listed above) or requires inpatient hospitalization or prolongation of existing hospitalization.
Time frame: Approximately 54 months
Population: The safety evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Epacadostat 25 mg BID | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | SAE | 0 Percentage of Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | TEAS | 100. Percentage of Participants |
| Phase 1: Epacadostat 50 mg BID | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | SAE | 40.0 Percentage of Participants |
| Phase 1: Epacadostat 50 mg BID | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | TEAS | 95.0 Percentage of Participants |
| Phase 1: Epacadostat 100 mg BID | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | TEAS | 94.4 Percentage of Participants |
| Phase 1: Epacadostat 100 mg BID | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | SAE | 50.0 Percentage of Participants |
| Phase 1: Epacadostat 300 mg BID | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | SAE | 45.0 Percentage of Participants |
| Phase 1: Epacadostat 300 mg BID | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | TEAS | 100. Percentage of Participants |
Primary
Phase 2: Objective Response Rate (ORR)
ORR was percentage of participants with best overall response \[complete response (CR) or partial response (PR)\], per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Approximately 54 months
Population: The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | NSCLC programmed cell death ligand (PD-L1) low negative (TPS < 50%) | 24.4 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Ovarian cancer | 8.1 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Transitional carcinoma of the genitourinary (GU) tract | 30.6 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Diffuse large B-cell lymphoma | 19.2 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Triple negative breast cancer | 11.1 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Microsatellite-instability high colorectal cancer | 43.8 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Gastric cancer | 22.2 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Hepatocellular carcinoma | 16.7 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Melanoma - immune checkpoint-naïve | 60.5 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Non-small cell lung cancer (NSCLC) (tumor proportion score (TPS) < 50% or indeterminate) | 30.8 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Renal cell carcinoma | 32.4 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Squamous cell carcinoma of the head and neck | 33.3 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Primary Refractory Melanoma | 0.0 percentage of participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Objective Response Rate (ORR) | Relapsed Melanoma | 0.0 percentage of participants |
Secondary
Phase 2: Duration of Disease Control
The duration of disease control is the time from the treatment start date to the first objective response of PD (by irRECIST v1.1 or Lugano Classification), death, or last tumor assessment date (if PD/death not present), for subjects with best overall response of SD or better.
Time frame: Up to 54 months
Population: The Efficacy Evaluable Population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type. The median time and the 90% CI were estimated using Kaplan-Meier method.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | Hepatocellular Carcinoma | 10.38 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | Triple Negative Breast Cancer | 11.47 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | Immune Checkpoint-naïve Melanoma | 30.29 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | Relapsed Melanoma | 4.21 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | NSCLC Total | 14.42 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | Renal Cell Carcinoma | 13.39 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | Squamous Cell Carcinoma of the Head and Neck | 9.18 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | Transitional Cell Carcinoma of the GU Tract | 15.36 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | Ovarian Cancer | 5.08 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | Gastric Cancer | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | MSI high Colorectal Cancer | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Disease Control | DLBCL | 7.29 Months |
Secondary
Phase 2: Duration of Response (DOR)
Duration of response is the time from the first overall response contributing to an objective response (complete or partial response) for DLBCL to the date of death or the date of first overall response of progressive diseasemeasured (by irRECIST for solid tumors or the Lugano Classification, whichever is earliest.
Time frame: Up to 54 months
Population: The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab).~Number analyzed indicated participants analyzed in the respective tumor type and those who responded.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | Triple Negative Breast Cancer | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | Immune Checkpoint-naïve Melanoma | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | Hepatocellular Carcinoma | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | NSCLC high positive (PD-L1 TPS ≥ 50%) | 12.44 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | NSCLC low/negative or indeterminate (PD-L1 TPS < 50% or indeterminate) | 11.93 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | NSCLC (TPS 0%) | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | NSCLC Unknown | 10.84 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | Renal Cell Carcinoma | 16.95 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | Squamous Cell Carcinoma of the Head and Neck | 11.33 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | Transitional Cell Carcinoma of the GU Tract | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | Ovarian Cancer | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | Gastric Cancer | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | MSI high Colorectal Cancer | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Duration of Response (DOR) | DLBCL | 3.66 Months |
Secondary
Phase 2: Ordinal Categorical Response Score
Ordinal categorical response score, determined by radiographic disease assessments per irRECIST v1.1. The 5-category ordinal response endpoint is determined at a given timepoint by classifying response into one of the following groups: 1 = Complete response per irRECIST v1.1 2 = Very good response, defined as \> 60% tumor reduction 3 = Minor response, defined as \> 30% to ≤ 60% tumor reduction 4 = Stable disease per irRECIST v1.1 5 = Progressive disease per irRECIST v1.1
Time frame: Up to 54 months
Population: The Efficacy Evaluable Population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Hepatocellular Carcinoma | Complete Response - Score 1 | 0 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Triple Negative Breast Cancer | Stable Disease - Score 4 | 7 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Triple Negative Breast Cancer | Progressive Disease - Score 5 | 19 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Triple Negative Breast Cancer | Unable to Evaluable | 6 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Immune Checkpoint-naïve Melanoma | Complete Response - Score 1 | 3 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Immune Checkpoint-naïve Melanoma | Very Good Response - Score 2 | 17 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Immune Checkpoint-naïve Melanoma | Minor Response - Score 3 | 6 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Relapsed Melanoma | Complete Response - Score 1 | 3 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Relapsed Melanoma | Very Good Response - Score 2 | 4 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Renal Cell Carcinoma | Stable Disease - Score 4 | 10 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Transitional Cell Carcinoma of the GU Tract | Minor Response - Score 3 | 5 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Ovarian Cancer | Progressive Disease - Score 5 | 16 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Ovarian Cancer | Unable to Evaluable | 7 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Gastric Cancer | Complete Response - Score 1 | 0 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Gastric Cancer | Unable to Evaluable | 9 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Renal Cell Carcinoma | Progressive Disease - Score 5 | 13 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Renal Cell Carcinoma | Unable to Evaluable | 2 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Squamous Cell Carcinoma of the Head and Neck | Complete Response - Score 1 | 3 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Squamous Cell Carcinoma of the Head and Neck | Very Good Response - Score 2 | 4 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Squamous Cell Carcinoma of the Head and Neck | Minor Response - Score 3 | 5 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Squamous Cell Carcinoma of the Head and Neck | Stable Disease - Score 4 | 8 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Squamous Cell Carcinoma of the Head and Neck | Progressive Disease - Score 5 | 10 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Squamous Cell Carcinoma of the Head and Neck | Unable to Evaluable | 6 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Transitional Cell Carcinoma of the GU Tract | Complete Response - Score 1 | 2 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Transitional Cell Carcinoma of the GU Tract | Very Good Response - Score 2 | 4 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Transitional Cell Carcinoma of the GU Tract | Stable Disease - Score 4 | 10 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Transitional Cell Carcinoma of the GU Tract | Progressive Disease - Score 5 | 11 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Transitional Cell Carcinoma of the GU Tract | Unable to Evaluable | 4 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Ovarian Cancer | Complete Response - Score 1 | 1 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Ovarian Cancer | Very Good Response - Score 2 | 0 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Ovarian Cancer | Minor Response - Score 3 | 2 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Ovarian Cancer | Stable Disease - Score 4 | 11 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Gastric Cancer | Very Good Response - Score 2 | 1 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Gastric Cancer | Minor Response - Score 3 | 5 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Gastric Cancer | Stable Disease - Score 4 | 1 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Gastric Cancer | Progressive Disease - Score 5 | 11 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | MSI high Colorectal Cancer | Complete Response - Score 1 | 1 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | MSI high Colorectal Cancer | Very Good Response - Score 2 | 3 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | MSI high Colorectal Cancer | Minor Response - Score 3 | 3 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | MSI high Colorectal Cancer | Stable Disease - Score 4 | 3 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | MSI high Colorectal Cancer | Progressive Disease - Score 5 | 5 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | MSI high Colorectal Cancer | Unable to Evaluable | 1 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Hepatocellular Carcinoma | Very Good Response - Score 2 | 2 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Hepatocellular Carcinoma | Minor Response - Score 3 | 2 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Hepatocellular Carcinoma | Stable Disease - Score 4 | 11 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Hepatocellular Carcinoma | Progressive Disease - Score 5 | 8 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Hepatocellular Carcinoma | Unable to Evaluable | 1 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Triple Negative Breast Cancer | Complete Response - Score 1 | 1 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Triple Negative Breast Cancer | Very Good Response - Score 2 | 1 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Triple Negative Breast Cancer | Minor Response - Score 3 | 2 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Immune Checkpoint-naïve Melanoma | Stable Disease - Score 4 | 5 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Immune Checkpoint-naïve Melanoma | Progressive Disease - Score 5 | 10 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Immune Checkpoint-naïve Melanoma | Unable to Evaluable | 2 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Primary Refractory Melanoma | Complete Response - Score 1 | 0 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Primary Refractory Melanoma | Very Good Response - Score 2 | 0 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Primary Refractory Melanoma | Minor Response - Score 3 | 0 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Primary Refractory Melanoma | Stable Disease - Score 4 | 0 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Primary Refractory Melanoma | Progressive Disease - Score 5 | 2 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Primary Refractory Melanoma | Unable to Evaluable | 1 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Relapsed Melanoma | Minor Response - Score 3 | 5 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Relapsed Melanoma | Stable Disease - Score 4 | 8 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Relapsed Melanoma | Progressive Disease - Score 5 | 10 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Relapsed Melanoma | Unable to Evaluable | 6 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | NSCLC | Complete Response - Score 1 | 4 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | NSCLC | Very Good Response - Score 2 | 3 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | NSCLC | Minor Response - Score 3 | 8 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | NSCLC | Stable Disease - Score 4 | 15 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | NSCLC | Progressive Disease - Score 5 | 24 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | NSCLC | Unable to Evaluable | 4 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Renal Cell Carcinoma | Complete Response - Score 1 | 2 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Renal Cell Carcinoma | Very Good Response - Score 2 | 6 Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Ordinal Categorical Response Score | Renal Cell Carcinoma | Minor Response - Score 3 | 4 Participants |
Secondary
Phase 2: Overall Survival (OS)
Overall survival is determined from the date of first dose until death due to any cause.
Time frame: Up to 54 months
Population: The Efficacy Evaluable Population included all participants enrolled in the study who received at least 1 dose of study drug. Number analyzed indicated participants analyzed in the respective tumor type. The median time and the 90% CI were estimated using Kaplan-Meier method.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | Immune Checkpoint-naïve Melanoma | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | Primary Refractory Melanoma | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | Hepatocellular Carcinoma | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | Triple Negative Breast Cancer | 5.16 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | Relapsed Melanoma | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | NSCLC | 14.62 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | Renal Cell Carcinoma | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | Squamous Cell Carcinoma of the Head and Neck | 8.34 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | Transitional Cell Carcinoma of the GU Tract | 13.44 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | Ovarian Cancer | 13.11 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | Gastric Cancer | 4.04 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | MSI high Colorectal Cancer | NA Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Overall Survival (OS) | DLBCL | 11.79 Months |
Secondary
Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events
Time frame: Up to 54 months
Population: The safety evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Treatment groups for this population were determined according to the actual treatment the participant receives on Day 1. All safety analyses were conducted using the safety evaluable population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Epacadostat 25 mg BID | Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | Treatment-Emergent Adverse Events (TEAE) | 100 Percentage of Participants |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events | Serious Treatment-Emergent Adverse Events | 51.0 Percentage of Participants |
Secondary
Phase 2: Progression Free Survival (PFS)
Progression-free survival is defined as number of days from the first day of taking study drug to the earlier of death or disease progression by irRECIST v1.1 for select solid tumors and modified Lugano Classification for DLBCL.
Time frame: Up to 54 months
Population: The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab).~Number analyzed indicated participants analyzed in the respective tumor type.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | Ovarian Cancer | 2.10 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | Gastric Cancer | 1.97 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | Hepatocellular Carcinoma | 5.49 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | Triple Negative Breast Cancer | 1.97 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | Immune Checkpoint-naïve Melanoma | 16.69 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | Primary Refractory Melanoma | 1.69 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | Relapsed Melanoma | 2.60 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | NSCLC | 4.09 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | Renal Cell Carcinoma | 4.50 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | Squamous Cell Carcinoma of the Head and Neck | 4.37 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | Transitional Cell Carcinoma of the GU Tract | 4.40 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | MSI high Colorectal Cancer | 6.11 Months |
| Phase 1: Epacadostat 25 mg BID | Phase 2: Progression Free Survival (PFS) | DLBCL | 2.63 Months |