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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02073123.
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).
Lead OrganizationNewLink Genetics Corporation
