Melanoma
Conditions
Keywords
Melanoma, Metastaic Melanoma
Brief summary
This is an adaptive clinical trial that includes a dose escalation phase followed by a randomized controlled Phase 3 trial. The purpose of the dose escalation phase is to establish the Phase 3 dose of indoximod in combination with pembrolizumab or nivolumab in subjects with unresectable or metastatic melanoma and evaluate PK. Subsequently the efficacy, safety and tolerability of indoximod plus pembrolizumab or nivolumab versus placebo plus pembrolizumab or nivolumab will be studied in subjects with unresectable or metastatic melanoma in the Phase 3 portion of the trial. The phase 3 study will not proceed per Sponsor decision.
Interventions
DRUGPembrolizumab
Pembrolizumab will be administered intravenously every 3 weeks starting on day 1.
DRUGNivolumab
Nivolumab will be administered intravenously every 2 weeks starting on day 1.
DRUGIndoximod
Indoximod will be administered orally every 12 hours starting at Day 1
Sponsors
NewLink Genetics Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically- or cytologically-confirmed unresectable stage III or stage IV melanoma not amenable to local therapy * At least one radiologically measurable lesion as per RECIST 1.1 * Have documentation of V600-activating BRAF mutation status or consent to BRAF V600 mutation testing during the screening period. * ECOG performance status 0 or 1 * Ability to ingest oral medications
Exclusion criteria
* Has Ocular Melanoma * Has received prior systemic treatment for unresectable or metastatic melanoma (except BRAF directed therapy). * Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or IDO1 inhibitor or any other antibody or drug specifically targeting checkpoint pathways other than anti-CTLA-4 which is permitted in the adjuvant setting. * Has received prior adjuvant therapy, monoclonal antibody or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) * Has received prior radiotherapy within 2 weeks of therapy. * Is pregnant or breast-feeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment. * Patients who have active, chronic, or on active treatment for Hep B or Hep C are excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Regimen-limiting Toxicities (RLTs) of Indoximod in Combination With Pembrolizumab | 28 Days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1 Pembrolizumab 200mg Q3 weeks and Indoximod 600mg Q12 hr | 7 |
| Dose Level 2 Pembrolizumab 200mg Q3 weeks and Indoximod 1200mg Q12 hr | 6 |
| Dose Level 3 Pembrolizumab 200mg Q3 weeks and Indoximod 1800mg Q12 hr | 8 |
| Total | 21 |
Baseline characteristics
| Characteristic | Dose Level 1 | Dose Level 2 | Dose Level 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 15.14 | 61.8 years STANDARD_DEVIATION 14.77 | 61.9 years STANDARD_DEVIATION 8.22 | 61.3 years STANDARD_DEVIATION 12.15 |
| Height | 171.3 Centimeters STANDARD_DEVIATION 10.56 | 168.8 Centimeters STANDARD_DEVIATION 8.86 | 172.9 Centimeters STANDARD_DEVIATION 10.25 | 171.1 Centimeters STANDARD_DEVIATION 9.59 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 8 Participants | 21 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Weight | 102.77 Kilograms STANDARD_DEVIATION 22.3 | 75.12 Kilograms STANDARD_DEVIATION 13.009 | 117.44 Kilograms STANDARD_DEVIATION 26.96 | 100.46 Kilograms STANDARD_DEVIATION 27.502 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 7 | 0 / 6 | 2 / 7 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 | 1 / 6 | 3 / 7 |
Outcome results
Primary
Number of Participants With Regimen-limiting Toxicities (RLTs) of Indoximod in Combination With Pembrolizumab
Time frame: 28 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Level 1 | Number of Participants With Regimen-limiting Toxicities (RLTs) of Indoximod in Combination With Pembrolizumab | 1 Participants |
| Dose Level 2 | Number of Participants With Regimen-limiting Toxicities (RLTs) of Indoximod in Combination With Pembrolizumab | 1 Participants |
| Dose Level 3 | Number of Participants With Regimen-limiting Toxicities (RLTs) of Indoximod in Combination With Pembrolizumab | 0 Participants |