Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer

March 16, 2026 updated by: NewLink Genetics Corporation

A Phase I/II Study of Indoximod in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Adenocarcinoma of the Pancreas

This phase I/II trial is designed to efficiently identify the regimen limiting toxicity (RLT) and recommended phase 2 dose (RP2D) for the combination of the immunotherapeutic agent indoximod when administered in combination with standard of care chemotherapy gemcitabine plus nab-paclitaxel in subjects with metastatic adenocarcinoma of the pancreas. All subjects will receive the same standard gemcitabine plus nab-paclitaxel regimen, plus indoximod in doses increasing from 600 mg twice daily to, potentially, 1200 mg twice daily.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a Phase I/II trial designed to evaluate the combination of the immunotherapeutic agent indoximod and the standard of care chemotherapy gemcitabine plus nab-paclitaxel in subjects with metastatic adenocarcinoma of the pancreas. The phase 1 portion is designed to identify the regimen-limiting toxicity (RLT) and recommended phase 2 dose (RP2D) for the combination. The phase 2 portion of the study will evaluate the potential efficacy of this combination. All subjects will receive the standard 28-day gemcitabine plus nab-paclitaxel regimen. Twice daily oral indoximod will be administered concurrently in continuous 28 day cycles.

In the phase 1 portion, dose escalation of indoximod will begin at 600 mg twice a day and potentially escalate to 1200 mg twice a day. There will be no intra-subject dose escalation. Regimen-limiting toxicity will be considered as those toxicities related to indoximod that significantly limit the administration of the backbone chemotherapy gemcitabine plus nab-paclitaxel. The period for determination of dose-limiting toxicities will be the initial 28 days of treatment. The recommended phase 2 dose will include an assessment of toxicities that occur at later time points.

Once a RP2D is determined, the phase 2 portion of the study will be initiated. In both phase 1 and phase 2, every 2 cycles subjects will have repeat imaging to assess response. Corollary biomarkers will be assessed at the same interval as will PET-CT after the 1st 8 week cycle. Up to 18 patients will be enrolled in the phase 1 portion of the study and 80 patients will be enrolled in the phase 2 portion.

Study Type

Interventional

Enrollment (Actual)

157

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Augusta University
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University Of Kentucy
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University in St. Louis
    • New Jersey
      • Paramus, New Jersey, United States, 07652
        • The Vally Hospital
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Greenville Health Systems
      • Spartanburg, South Carolina, United States, 29303
        • Gibbs Cancer Center and Research Institute
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • The West Clinic
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Center
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient has definitive histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cell or neuroendocrine neoplasms are excluded.
  • Initial diagnosis of metastatic disease must have occurred ≤8 weeks prior to entry in the study.
  • Patient has one or more metastatic tumors measurable per RECIST 1.1 by CT scan ≤4 weeks prior to entry into the study
  • Male or non-pregnant and non-lactating female, and ≥18 years of age.
  • Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
  • Prior treatment with gemcitabine and/or nab-paclitaxel in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.
  • Patients cannot have received any other immunomodulatory therapies (including vaccines) as treatment for this or any other cancer.
  • Patient has a Karnofsky performance status (KPS) ≥ 70.
  • Patients should be asymptomatic for jaundice prior to Day 1.

Exclusion Criteria:

  • Patients may not be receiving (or received prior to enrollment) any other investigational agents for metastatic disease.
  • Patient has known brain metastases,
  • Patient has only locally advanced disease.
  • Lymph node only metastases even if considered M1 disease by official staging criteria.
  • History of malignancy in the last 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 3 years.
  • Patients with any active autoimmune disease
  • Patient has undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Indoximod and Gemcitabine + Nab-paclitaxel - Phase 1
Participants received indoximod (600mg, 100mg, or 1200mg according to their assigned dose cohort) PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity.
Drug: Nab-Paclitaxel
Nab-Paclitaxel 125 mg/m^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity.
Other Names:
  • Abraxane
  • Paclitaxel
Drug: Gemcitabine
Gemcitabine 1000 mg/m^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity.
Other Names:
  • Gemzar
Drug: Indoximod
Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.
Other Names:
  • 1-methyl-D-tryptophan
  • D-1MT
Experimental: Indoximod and Gemcitabine + Nab-paclitaxel - Phase 2
Oral indoximod 1200mg BID concurrent with the first backbone chemotherapy cycle. Patients will receive gemcitabine plus nab-paclitaxel on a standard 4 week cycle schedule. Oral indoximod at 1200mg BID will continue throughout.
Drug: Nab-Paclitaxel
Nab-Paclitaxel 125 mg/m^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity.
Other Names:
  • Abraxane
  • Paclitaxel
Drug: Gemcitabine
Gemcitabine 1000 mg/m^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity.
Other Names:
  • Gemzar
Drug: Indoximod
Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.
Other Names:
  • 1-methyl-D-tryptophan
  • D-1MT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Regimen Limiting Toxicity
Time Frame: 10 months

Phase 1 component:

To identify the regimen limiting toxicity (RLT) for the combination of the immunotherapeutic agent indoximod when administered in combination with standard of care chemotherapy gemcitabine plus nab-paclitaxel in subjects with metastatic adenocarcinoma of the pancreas.

RLT will be considered as only grade 3 and 4 toxicities that are attributable to the test agent and result in the delay of the administration of the backbone chemotherapy, gemcitabine plus nab-paclitaxel.
10 months
Overall Survival
Time Frame: 22 months

Phase 2 component:

To evaluate efficacy as determined by overall survival (OS) in patients with metastatic adenocarcinoma of the pancreas.
22 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate
Time Frame: 22 months
To determine the response rate of the combination indoximod with gemcitabine plus nab-paclitaxel. Imaging assessments to be performed at protocol-specified time points and evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
22 months
Progression Free Survival
Time Frame: 22 months
Time to progression with the combination indoximod with gemcitabine plus nab-paclitaxel. Progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
22 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NewLink Genetics Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2014

Primary Completion (Actual)

January 17, 2018

Study Completion (Actual)

October 17, 2018

Study Registration Dates

First Submitted

February 28, 2014

First Submitted That Met QC Criteria

February 28, 2014

First Posted (Estimated)

March 4, 2014

Study Record Updates

Last Update Posted (Actual)

April 3, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NLG2104

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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