The indoleamine 2,3-dioxygenase ( IDO ) pathway is a key counter-regulatory mechanism that normally inhibits immune responses when appropriate.
In the setting of cancer, IDO pathway-mediated immune suppression is exploited by tumors in order to prevent and defeat anti-tumor immunity.
Small-molecule inhibitors of the IDO pathway, such as Indoximod ( IDO inhibitor ), are an increasingly validated class of potential cancer therapeutics.
Additionally, pre-clinical tumor models have shown complementary effects with Indoximod / anti-PD1 checkpoint inhibitor treatment combinations.
A clinical trial was developed based upon these data.
Upon successful completion of a phase 1b dose escalation cohort, metastatic melanoma patients were enrolled in a single arm phase 2 trial evaluating the addition of Indoximod to standard of care checkpoint inhibitors approved for melanoma.
The large majority of patients received Indoximod with Pembrolizumab ( Keytruda ) and this interim report is limited to those patients. Indoximod was administered continuously in 21 days cycles ( 1200mg po twice daily ) concurrently with Pembrolizumab ( 3mg/kg q21 days ).
Study endpoint was best overall response ( objective response rate [ ORR ] = complete response rate [ CR ] + partial response rate [ PR ] ) per site reported RECIST criteria.
At time of data cut-off, 60 patients had received Indoximod and Pembrolizumab and were evaluable for response, defined as having at least one follow-up imaging study performed.
The ORR was 52% ( 31/60 ) with a CRR of 8% ( 5/60 ).
The combination was well tolerated. The most frequently reported adverse events ( regardless of attribution ), occurring in greater than or equal to 20% of subjects, were fatigue, diarrhea, nausea, arthralgia, headache, cough, rash, pruritus, and hypertension.
The most frequently reported laboratory abnormalities ( regardless of attribution ), were anemia ( 17% ) and hyperglycemia ( 17% ).
In conclusion, the interim analysis of the combination of Indoximod and Pembrolizumab has demonstrated an ORR of 52% which compares favorably with the established ORR for Pembrolizumab alone. ( Xagena )
Source: American Association for Cancer Research ( AACR ) Meeting, 2017