NCT02073123

Study of IDO Inhibitor in Combination With Checkpoint Inhibitors for Adult Patients With Metastatic Melanoma

A Phase 1/2 Study of the Concomitant Administration of Indoximod Plus Immune Checkpoint Inhibitors for Adult Patients With Advanced or Metastatic Melanoma

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 132 (actual)
• Sponsor: NewLink Genetics Corporation · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 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).

Conditions

• Metastatic Melanoma
• Stage III Melanoma
• Stage IV Melanoma

Interventions

Type	Name	Description
DRUG	Indoximod	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
DRUG	Ipilimumab	Ipilimumab administered intravenously at 3 mg/kg every three weeks for a total of four doses.
DRUG	Nivolumab	Nivolumab administered intravenously at 240 mg every 2 weeks.
DRUG	Pembrolizumab	Pembrolizumab administered intravenously at 2 mg/kg every three weeks.

Timeline

• Start date: 2014-07-01
• Primary completion: 2018-01-17
• Completion: 2019-07-03
• First posted: 2014-02-27
• Last updated: 2020-06-05

Locations

6 sites across 1 country: United States