Epacadostat is an oral, potent, selective inhibitor of indoleamine 2,3-dioxygenase 1 ( IDO1 ), a tryptophan-catabolizing enzyme that induces immune tolerance by T-cell suppression.
Preliminary phase 1 results from this ongoing study of Epacadostat with Pembrolizumab ( Keytruda ) have shown promising clinical activity and an acceptable safety profile ( Gangadhar et al, SITC 2015; Hamid et al, SMR 2015 ).
Updated data from all 62 phase 1 patients as of 28 March 2016 are reported.
Patients with advanced melanoma and select solid tumors were enrolled; patients previously treated with checkpoint inhibitors were excluded.
Enrollment is complete for dose escalation ( Epacadostat 25, 50, 100 mg BID + Pembrolizumab 2 mg/kg IV Q3W or Epacadostat 300 mg BID + Pembrolizumab 200 mg IV Q3W ) and dose expansion ( Epacadostat 50, 100, and 300 mg BID + Pembrolizumab 200 mg IV Q3W ).
Safety, tolerability, and response ( RECIST 1.1 ) were evaluated.
The MTD ( maximum tolerated dose ) has not been established.
The most common ( greater than or equal to 15% ) all-grade treatment-related adverse effects ( TRAEs ) were fatigue, rash, arthralgia, pruritus, diarrhea, and nausea.
Grade greater than or equal to 3 TRAEs were observed in 18% ( most common: rash [ 8% ] and increased lipase [ 3% ] ).
No treatment-related deaths occurred.
Among 19 patients who were treatment-naive for advanced melanoma ( M1c 53% ), 4 CRs [ complete responses ], 7 PRs [ partial responses ], and 3 SDs [ stable diseases ] were observed.
Responses were observed in all Epacadostat dose cohorts greater than or equal to 50 mg BID and all sites of target lesions including liver, lung, and lymph nodes.
All responses are confirmed and ongoing ( median follow-up [ min, max ]: 42 weeks [ 31.7, 75.9 ] ).
Median progression-free survival [ PFS ] has not been reached.
Responses were also observed in patients previously treated for advanced melanoma ( n = 3; 1 CR, 1 SD ) and patients with NSCLC [ non-small-cell lung carcinoma ] ( n = 12; 5 PRs, 2 SDs ), RCC [ renal cell carcinoma ] ( n = 11; 3 PRs, 5 SDs ), endometrial adenocarcinoma ( n = 7; 1 CR, 1 PR ), TCC [ transitional cell carcinoma ] ( n = 5; 3 PRs ), TNBC [ triple-negative breast cancer ] ( n = 3; 2 SDs ), SCCHN [ squamous cell carcinoma of the head and neck ] ( n = 2; 1 PR, 1 SD ).
Based on overall safety and efficacy, Epacadostat 100 mg BID was selected as the RP2D ( Recommended Phase II Dose ).
In conclusion, Epacadostat with Pembrolizumab continues to be well tolerated and showed promising clinical activity.
Based on these results, enrollment in tumor-specific cohorts is ongoing in phase 2 of this study and a phase 3 study in patients who are treatment-naive for advanced melanoma has been initiated, ( Xagena )
Source: ESMO Meeting, 2016