A Study of Indoximod or Placebo Plus Pembrolizumab or Nivolumab for Subjects With Unresectable or Metastatic Melanoma (NLG2107)

A Phase 2/3 (Adaptive Design) Study of the Concomitant Administration of Indoximod or Placebo Plus Pembrolizumab or Nivolumab in Adult Patients With Unresectable Stage III or Stage IV Malignant Melanoma

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.

Study Overview

• Status: Terminated
• Conditions: Melanoma
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Indoximod; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Comprehensive Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Utah Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + Indoximiod	Drug: Pembrolizumab; Pembrolizumab will be administered intravenously every 3 weeks starting on day 1.; Other Names: Keytruda; Drug: Indoximod; Indoximod will be administered orally every 12 hours starting at Day 1
Experimental: Nivolumab + Indoximiod	Drug: Indoximod; Indoximod will be administered orally every 12 hours starting at Day 1; Drug: Nivolumab; Nivolumab will be administered intravenously every 2 weeks starting on day 1.; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Regimen-limiting Toxicities (RLTs) of Indoximod in Combination With Pembrolizumab	28 Days

Collaborators and Investigators

• Sponsor: NewLink Genetics Corporation

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2017
• Primary Completion (Actual): October 21, 2019
• Study Completion (Actual): November 4, 2019

Study Registration Dates

• First Submitted: September 29, 2017
• First Submitted That Met QC Criteria: September 29, 2017
• First Posted (Actual): October 4, 2017

Study Record Updates

• Last Update Posted (Actual): September 27, 2022
• Last Update Submitted That Met QC Criteria: September 2, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Melanoma, Metastaic Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Pembrolizumab
• Other Study ID Numbers: NLG2107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No