Updated data from the advanced non-small cell lung cancer ( NSCLC ) patient cohort of the ongoing phase 1/2 ECHO-202 trial, evaluating Epacadostat, a selective IDO1 enzyme inhibitor, in combination with Pembrolizumab ( Keytruda ), an anti-PD-1 therapy, were presented at the 2017 American Society of Clinical Oncology ( ASCO ) Annual Meeting in Chicago.
Data showed an overall response rate ( ORR ) of 35% ( n=14/40 ) among all patients with advanced squamous and non-squamous NSCLC treated with the combination of Epacadostat and Pembrolizumab, irrespective of PD-L1 status.
Indoleamine 2,3-dioxygenase 1 ( IDO1 ) is a key immunosuppressive enzyme that modulates the anti-tumor immune response by promoting regulatory T cell generation and blocking effector T cell activation, thereby facilitating tumor growth by allowing cancer cells to avoid immune surveillance.
Epacadostat is an investigational, highly potent and selective oral inhibitor of the IDO1 enzyme that regulates the tumor immune microenvironment, thereby restoring effective anti-tumor immune responses.
In single-arm studies, the combination of Epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma. In these studies, Epacadostat combined with the CTLA-4 inhibitor Ipilimumab or the PD-1 inhibitor Pembrolizumab improved response rates compared with studies of the immune checkpoint inhibitors alone.
Data at ASCO ( as of February 27, 2017 ) have shown an ORR of 35% ( n=14/40 ) among all patients with advanced NSCLC treated with the combination of Epacadostat and Pembrolizumab, with a complete response ( CR ) in two patients ( 5% ) and partial response ( PR ) in 12 patients ( 30% ).
The data have shown a disease control rate ( DCR ) of 63% ( n=25/40 ), with 71% ( n=10/14 ) of responses ongoing at the time of the data cut-off ( duration of response, range: 8.9 to 76.6+ weeks ).
Responses were observed in patients with high levels of PD-L1 expression [ tumor proportion score ( TPS ) greater than or equal to 50% ], as well as in those patients with lower levels of PD-L1 expression ( TPS of less than 50% ).
All responses were observed in the subgroup of patients with zero to two prior lines of therapy for advanced disease.
Among patients treated with Pembrolizumab in combination with Epacadostat greater than or equal to 100 mg twice daily, the ORR was 40% ( n=14/35 ).
The most common treatment-related adverse events ( TRAEs ) for Epacadostat plus Pembrolizumab included fatigue ( 28% ), arthralgia ( 17% ), nausea ( 14% ), decreased appetite ( 10% ), pruritus ( 10% ), and rash ( 10% ).
Grade greater than or equal to 3 TRAEs that occurred in more than 1 patient were limited to lipase increased ( n=3 ), fatigue ( n=2 ), and rash ( n=2 ).
TRAEs led to discontinuation of treatment in 5% of study patients.
The safety profile was consistent with previously reported phase 1 findings, as well as the phase 1/2 safety results in other tumor cohorts and pooled safety data from this study.
In general, the safety profile of the combination was also consistent with Pembrolizumab monotherapy.
The ECHO-202 study is evaluating the safety and efficacy of Epacadostat, a selective IDO1 inhibitor, in combination with Pembrolizumab.
Patients previously treated with anti-PD-1 or anti-CTLA-4 therapies were excluded from this trial.
Enrollment is complete for the phase 1 dose escalation ( Epacadostat 25, 50, 100 mg BID + Pembrolizumab 2 mg/kg IV Q3W and Epacadostat 300 mg BID + Pembrolizumab 200 mg IV Q3W ) and phase 1 dose expansion ( Epacadostat 50, 100, and 300 mg BID + Pembrolizumab 200 mg IV Q3W ) portions of the trial. ( Xagena )
Source: ASCO Meeting, 2017