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

• ClinicalTrials.gov Identifier: NCT03301636
• Recruitment Status: Terminated
• First Posted: October 4, 2017
• Last Update Posted: June 5, 2020
• Sponsor: NewLink Genetics Corporation
• Information provided by (Responsible Party): Lumos Pharma ( NewLink Genetics Corporation )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Melanoma	Drug: Pembrolizumab; Drug: Nivolumab; Drug: Indoximod	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 8, 2017
• Actual Primary Completion Date: October 21, 2019
• Actual Study Completion Date: November 4, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Evaluation of safety and tolerability of indoximod in combination with pembrolizumab or nivolumab measured by number of subjects with regimen-limiting toxicities (RLTs) [ Time Frame: 28 Days ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Iowa

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States, 52242

United States, Minnesota

Mayo Clinic - Rochester

Rochester, Minnesota, United States, 55905

United States, New Mexico

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, United States, 87102

United States, Utah

Utah Cancer Specialists

Salt Lake City, Utah, United States, 84102

Sponsors and Collaborators

NewLink Genetics Corporation

More Information

• Responsible Party: NewLink Genetics Corporation
• ClinicalTrials.gov Identifier: NCT03301636
• Other Study ID Numbers: NLG2107
• First Posted: October 4, 2017
• Last Update Posted: June 5, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lumos Pharma ( NewLink Genetics Corporation ):

Melanoma, Metastaic Melanoma

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Pembrolizumab; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action