Metastatic MelanomaPhase 1/2NCT02073123
Study of IDO Inhibitor in Combination With Checkpoint Inhibitors for Adult Patients With Metastatic Melanoma
A Phase 1/2 study testing Indoximod, Ipilimumab and Nivolumab in people with Metastatic Melanoma and Stage III Melanoma, run by NewLink Genetics Corporation at 6 sites in United States.
Trial summary
To evaluate the preliminary efficacy of the established dose of indoximod in combination with immune checkpoint inhibition as measured by the best overall response rate (ORR) (complete response (CR) + partial response (PR))across both standard of care agents administered sequentially in patients with unresectable… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma, Stage III Melanoma, Stage IV Melanoma
- What is being tested?
- Indoximod, Ipilimumab and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 131 participants
- Where
- 6 sitesUnited States
- Study dates
- Jul 2014to 3 Jul 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Unresectable Stage III or Stage IV melanoma.
- Patients must have measurable disease, defined as lesions that can be accurately measure in in 2 perpendicular diameters with at least one diameter > 20mm and the other >10mm on conventional CT or MRI or 10mm x 10 mm by spiral CT.
- No systemic treatment in the previous 28 days.
- Age ≥18 years. Because no dosing or adverse event data are currently available on the use of ipilimumab or indoximod in patients <18 years of age, children are excluded from this study.
- ECOG performance status ≤2 (Karnofsky ≥60% )
- Patients with known brain metastases will only be eligible after their tumors have been treated with definitive resection and/or radiotherapy and they are neurologically stable for at least 1 month off steroids.
Who cannot join
- Patients who have had molecular targeted therapy (including vemurafenib) or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients who have had prior therapy with immune checkpoint inhibition or or indoximod are excluded from the trial.
- Any other cancer, unless the patient has been disease-free for ≥5 years
- Patients with laboratory evidence of pancreatitis are excluded.
- Patients with autoimmune disease
- Chronic use of immune-suppressive drugs (ie, systemic corticosteroids used in the management of cancer or non-cancer related illnesses, eg, COPD).
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
New Mexico Cancer Center Alliance
Albuquerque, New Mexico, 87106
Augusta University
Augusta, Georgia, 30912
Penn State Hershey Cancer Institue
Hershey, Pennsylvania, 17033
University of Iowa Hospital and Clinics
Iowa City, Iowa, 52242
Mayo Clinic
Rochester, Minnesota, 55905
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: A Phase 1/2 Study of the Concomitant Administration of Indoximod Plus Immune Checkpoint Inhibitors for Adult Patients With Advanced or Metastatic Melanoma
To evaluate the preliminary efficacy of the established dose of indoximod in combination with immune checkpoint inhibition as measured by the best overall response rate (ORR) (complete response (CR) + partial response (PR))across both standard of care agents administered sequentially in patients with unresectable stage III or stage IV melanoma
Read the detailed description
The incidence of melanoma is increasing. Based upon data obtained between 2004 and 2006, the lifetime probability of developing melanoma in the United States is estimated to be 1 in 37 for men and 1 in 56 for women. In the United States, melanoma is the fifth leading cancer in men and the seventh in women. Locally confined, fully-resectable disease may be curable with current therapy; but Stage IV metastatic disease (or relapsed/recurrent disease) is highly refractory to therapy. Thus, experimental clinical trials provide an accepted treatment option for metastatic or relapsed/refractory melanoma.
The current study is designed as a prospective trial to evaluate the combination of indoximod and checkpoint inhibitors in adult patients with metastatic melanoma. Ipilimumab, pembrolizumab and nivolumab will be used at the recommended approved doses for this indication.
The current trial will be done in two phases: a Phase 1b dose escalation of indoximod in combination with ipilimumab, starting at half the recommended single-agent dose, to establish the recommended Phase 2 dose for the combination.
This will be followed by a three arm expansion study testing a fixed dose of indoximod (at the recommended Phase 2 dose) combined with standard-dose ipilimumab, pembrolizumab or nivolumab.
Treatment will be administered on an outpatient basis. No investigational or commercial cancer directed agents or therapies other than those described below may be administered.
Safety assessment will follow the guidelines provided in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version.4.03.
Patients will be followed both clinically and radiographically starting 12 weeks after initiation of treatment then every 8 weeks for tumor evaluation. Post-treatment scans will be compared to the baseline scan and responses will be assessed based using mWHO and immune related response criteria (irRC) described by Wolchok et al. (Wolchok et al., 2009).
- Conditions
- Metastatic Melanoma, Stage III Melanoma, Stage IV Melanoma
- Being tested
- Indoximod, Ipilimumab, Nivolumab, Pembrolizumab
- Keywords
- Metastatic melanoma, Stage III melanoma, Stage IV melanoma, unresectable
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IndoximodDrug
Also called 1-methyl-D-tryptophan, D-1MT
Initial dose of 600mg BID by mouth with escalation planned to 1200mg BID by mouth
Dose escalation:
- If 0 of the 3 subjects forming the first cohort experience RLT, 1200mg BID cohort will be enrolled
- If 1 of the 3 subjects in any cohort experiences a RLT, then enrollment into that cohort will increase to a total of 6 subjects
- If > 1 of the 3-6 subjects experience a RLT, then the MTD has been exceeded and further enrollment into the cohort will cease
- If >1 subject at 600mg BID experiences a RLT, the dose will be de-escalated to 400mg BID. If >1 subject at this level experiences a RLT, one additional de-escalation to 200mg BID is allowed
Dosing cycles are 21 days in length during the combination immunotherapy component (first 4 cycles) and 28 days during indoximod monotherapy. Patients will continue until they experience disease progression or limiting toxicity
Phase 2 Treatment Plan (Cohort 2) Will receive fixed dose of indoximod determined in phase 1
IpilimumabDrug
Also called YERVOY, MDX-010, MDX-101
Ipilimumab administered intravenously at 3 mg/kg every three weeks for a total of four doses.
NivolumabDrug
Nivolumab administered intravenously at 240 mg every 2 weeks.
PembrolizumabDrug
Pembrolizumab administered intravenously at 2 mg/kg every three weeks.
| Study group | Role | What they receive |
|---|---|---|
| Indoximod + Ipilimumab | Experimental | Indoximod will be administered at 1200mg BID by mouth.
Ipilimumab administered intravenously at 3 mg/kg every three weeks for a total of four doses.
Indoximod and ipilimumab will be dosed concurrently. Indoximod will be dosed twice daily on all days of each 21 day cycles (segment 1). Ipilimumab will be dosed on the 1st day of each 21 day cycle for the first 4 cycles. Indoximod dosing will continue after all 4 doses of ipilimumab are administered (segment 2, 28-day cycles).
Patients will continue until they experience disease progression or limiting toxicity. Receives: Drug: Indoximod; Drug: Ipilimumab |
| Indoximod + Pembrolizumab | Experimental | Indoximod will be administered at 1200mg BID by mouth.
Pembrolizumab administered intravenously at 2 mg/kg every three weeks. Receives: Drug: Indoximod; Drug: Pembrolizumab |
| Indoximod + Nivolumab | Experimental | Indoximod will be administered at 1200mg BID by mouth.
Nivolumab administered intravenously at 240 mg every 2 weeks. Receives: Drug: Indoximod; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1 Regimen Limiting Toxicity of the Combination of Indoximod and Ipilimumab
Number subjects with at least one RLTs observed in each dose level.
Measured: 6 weeks
Overall Response Rate
Phase 2 component: To evaluate the preliminary efficacy of the established dose of indoximod in combination with immune checkpoint inhibition as measured by the best overall response rate in patients with unresectable Stage III or Stage IV melanoma.
Measured: 22 months
Secondary outcomes (3)
Overall Survival
Phase 2 component: Overall survival (OS) and 95% confidence interval
Measured: 24 months
Progression Free Survival
Phase 2 component: Time to progression with the combination indoximod with checkpoint inhibitor. Progression will be evaluated in this study using Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
Measured: 24 months
Disease Control Rate
Phase 2 component: Disease control rate (CR, PR or SD)
Measured: 22 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2014 (estimated)
- Study startJul 2014
- Primary completion17 Jan 2018
- Study completion3 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- NewLink Genetics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02073123
- Sponsor's protocol ID
- NLG2103
- Status last verified
- May 2026
- First submitted
- 25 Feb 2014
- Last updated
- 29 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of the Concomitant Administration of Indoximod Plus Immune Checkpoint Inhibitors for Adult Patients With Advanced or Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT02073123
- Acronym / sponsor ID
- NLG2103
- Conditions
- Metastatic Melanoma, Stage III Melanoma, Stage IV Melanoma
- Keywords
- Metastatic melanoma, Stage III melanoma, Stage IV melanoma, unresectable
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- NewLink Genetics CorporationIndustry (pharma, biotech, devices)
- Study start
- Jul 2014 (actual)
- Primary completion
- 17 Jan 2018 (actual)
- Study completion
- 3 Jul 2019 (actual)
- First posted
- 27 Feb 2014 (estimated)
- Results
- Posted 29 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the preliminary efficacy of the established dose of indoximod in combination with immune checkpoint inhibition as measured by the best overall response rate (ORR) (complete response (CR) + partial response (PR))across both standard of care agents administered sequentially in patients with unresectable stage III or stage IV melanoma
Detailed description
The incidence of melanoma is increasing. Based upon data obtained between 2004 and 2006, the lifetime probability of developing melanoma in the United States is estimated to be 1 in 37 for men and 1 in 56 for women. In the United States, melanoma is the fifth leading cancer in men and the seventh in women. Locally confined, fully-resectable disease may be curable with current therapy; but Stage IV metastatic disease (or relapsed/recurrent disease) is highly refractory to therapy. Thus, experimental clinical trials provide an accepted treatment option for metastatic or relapsed/refractory melanoma.
The current study is designed as a prospective trial to evaluate the combination of indoximod and checkpoint inhibitors in adult patients with metastatic melanoma. Ipilimumab, pembrolizumab and nivolumab will be used at the recommended approved doses for this indication.
The current trial will be done in two phases: a Phase 1b dose escalation of indoximod in combination with ipilimumab, starting at half the recommended single-agent dose, to establish the recommended Phase 2 dose for the combination.
This will be followed by a three arm expansion study testing a fixed dose of indoximod (at the recommended Phase 2 dose) combined with standard-dose ipilimumab, pembrolizumab or nivolumab.
Treatment will be administered on an outpatient basis. No investigational or commercial cancer directed agents or therapies other than those described below may be administered.
Safety assessment will follow the guidelines provided in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version.4.03.
Patients will be followed both clinically and radiographically starting 12 weeks after initiation of treatment then every 8 weeks for tumor evaluation. Post-treatment scans will be compared to the baseline scan and responses will be assessed based using mWHO and immune related response criteria (irRC) described by Wolchok et al. (Wolchok et al., 2009).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Indoximod + Ipilimumab | Experimental | Drug: Indoximod, Drug: IpilimumabIndoximod will be administered at 1200mg BID by mouth. Ipilimumab administered intravenously at 3 mg/kg every three weeks for a total of four doses. Indoximod and ipilimumab will be dosed concurrently. Indoximod will be dosed twice daily on all days of each 21 day cycles (segment 1). Ipilimumab will be dosed on the 1st day of each 21 day cycle for the first 4 cycles. Indoximod dosing will continue after all 4 doses of ipilimumab are administered (segment 2, 28-day cycles). Patients will continue until they experience disease progression or limiting toxicity. |
| Indoximod + Pembrolizumab | Experimental | Drug: Indoximod, Drug: PembrolizumabIndoximod will be administered at 1200mg BID by mouth. Pembrolizumab administered intravenously at 2 mg/kg every three weeks. |
| Indoximod + Nivolumab | Experimental | Drug: Indoximod, Drug: NivolumabIndoximod will be administered at 1200mg BID by mouth. Nivolumab administered intravenously at 240 mg every 2 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Unresectable Stage III or Stage IV melanoma.
- Patients must have measurable disease, defined as lesions that can be accurately measure in in 2 perpendicular diameters with at least one diameter > 20mm and the other >10mm on conventional CT or MRI or 10mm x 10 mm by spiral CT.
- No systemic treatment in the previous 28 days.
- Age ≥18 years. Because no dosing or adverse event data are currently available on the use of ipilimumab or indoximod in patients <18 years of age, children are excluded from this study.
- ECOG performance status ≤2 (Karnofsky ≥60% )
Key exclusion criteria (6 listed)
- Patients who have had molecular targeted therapy (including vemurafenib) or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients who have had prior therapy with immune checkpoint inhibition or or indoximod are excluded from the trial.
- Any other cancer, unless the patient has been disease-free for ≥5 years
- Patients with laboratory evidence of pancreatitis are excluded.
- Patients with autoimmune disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IndoximodAlso: 1-methyl-D-tryptophan, D-1MTInitial dose of 600mg BID by mouth with escalation planned to 1200mg BID by mouth Dose escalation: * If 0 of the 3 subjects forming the first cohort experience RLT, 1200mg BID cohort will be enrolled * If 1 of the 3 subjects in any cohort experiences a RLT, then enrollment into that cohort will increase to a total of 6 subjects * If > 1 of the 3-6 subjects experience a RLT, then the MTD has been exceeded and further enrollment into the cohort will cease * If >1 subject at 600mg BID experiences a RLT, the dose will be de-escalated to 400mg BID. If >1 subject at this level experiences a RLT, one additional de-escalation to 200mg BID is allowed Dosing cycles are 21 days in length during the combination immunotherapy component (first 4 cycles) and 28 days during indoximod monotherapy. Patients will continue until they experience disease progression or limiting toxicity Phase 2 Treatment Plan (Cohort 2) Will receive fixed dose of indoximod determined in phase 1 | Drug | Indoximod + Ipilimumab, Indoximod + Nivolumab, Indoximod + Pembrolizumab |
| IpilimumabAlso: YERVOY, MDX-010, MDX-101Ipilimumab administered intravenously at 3 mg/kg every three weeks for a total of four doses. | Drug | Indoximod + Ipilimumab |
| NivolumabNivolumab administered intravenously at 240 mg every 2 weeks. | Drug | Indoximod + Nivolumab |
| PembrolizumabPembrolizumab administered intravenously at 2 mg/kg every three weeks. | Drug | Indoximod + Pembrolizumab |
Primary outcome
Phase 1 Regimen Limiting Toxicity of the Combination of Indoximod and Ipilimumab
Time frame: 6 weeks
Number subjects with at least one RLTs observed in each dose level.
Overall Response Rate
Time frame: 22 months
Phase 2 component: To evaluate the preliminary efficacy of the established dose of indoximod in combination with immune checkpoint inhibition as measured by the best overall response rate in patients with unresectable Stage III or Stage IV melanoma.
3 secondary outcomes
Overall Survival
Time frame: 24 months
Progression Free Survival
Time frame: 24 months
Disease Control Rate
Time frame: 22 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Study Sponsor WebsiteLink provided by the sponsor.
Related trials for Metastatic Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 3
A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)
Melanoma
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 1/2
A Study of ST-1898 for Unresectable or Metastatic Melanoma
Unresectable or Metastatic Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Indoximod, Ipilimumab and Nivolumab in people with Metastatic Melanoma and Stage III Melanoma, run by NewLink Genetics Corporation at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1 Regimen Limiting Toxicity of the Combination of Indoximod and Ipilimumab (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.