Updated data from the ongoing phase 1/2 ECHO-204 trial evaluating the safety and efficacy of Epacadostat, an oral selective IDO1 enzyme inhibitor, in combination with Nivolumab ( Opdivo ), a PD-1 immune checkpoint inhibitor, in multiple advanced solid tumors were presented at the American Society of Clinical Oncology ( ASCO ) annual meeting in Chicago, Illinois.
The data have shown that in patients with advanced melanoma treated with Epacadostat ( 100 mg or 300 mg ) plus Nivolumab ( n=40 ), the combined objective response rate ( ORR ) was 63% ( 25/40 ), including 2 complete responses ( CRs ) and 23 partial responses ( PRs ), and the combined disease control rate ( DCR ) was 88% ( 35/40 ).
In previously-treated patients with squamous cell carcinoma of the head and neck ( SCCHN ) who were treated with Epacadostat ( 100 mg or 300 mg ) plus Nivolumab ( n=31 ), the combined ORR was 23% ( 7/31 ), including 1 CR and 6 PRs, and the combined DCR was 61% ( 19/31 ).
Responses for melanoma and squamous cell carcinoma of the head and neck were observed regardless of PD-L1 expression and HPV status ( in SCCHN ), and all responses were ongoing at the data cutoff ( February 13, 2017 ).
Epacadostat plus Nivolumab did not demonstrate an efficacy signal in the unselected refractory ovarian cancer and colorectal cancer patient populations.
The clinical responses in the ECHO-204 trial in patients with melanoma and SCCHN who were treated with the combination of Epacadostat and Nivolumab further underscore the rationale for studying the therapeutic utility of IDO1 enzyme inhibition plus PD-1 blockade.
These preliminary phase 1/2 data support further investigation of this novel immunotherapy combination in the planned phase 3 programs.
Epacadostat plus Nivolumab was generally well-tolerated in patients with select advanced solid tumors.
In phase 1 ( dose escalation ), 36 patients were enrolled and no dose-limiting toxicities were observed.
Among the 230 patients enrolled in phase 2, the most frequent treatment-related adverse events ( TRAEs ) ( greater than or equal to 10% ) in patients receiving Epacadostat 100 mg BID ( 69/230 ) or 300 mg BID (1 61/230 ) and Opdivo were rash ( 35% and 32%, respectively ), fatigue ( 23% and 38%, respectively ), and nausea ( 19% and 21%, respectively ).
Rash was the most common grade 3/4 TRAE ( 10% [ Epacadostat 100 mg BID ] and 15% [ Epacadostat 300 mg BID ] ).
TRAEs led to discontinuation in 6% ( 100 mg ) and 12% ( 300 mg ) of patients.
There were no treatment-related deaths.
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, first-in-class, 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.
The ECHO-204 study is a phase 1/2 study evaluating the safety and efficacy of Epacadostat in combination with Nivolumab in subjects with select advanced solid tumors and lymphomas, including melanoma, non-small cell lung cancer, colorectal cancer, squamous cell carcinoma of the head and neck, ovarian cancer, and B cell non-Hodgkin lymphoma or Hodgkin lymphoma ( in phase 2, diffuse large B-cell lymphoma was the only non-Hodgkin lymphoma sub-type permitted ).
Patients previously treated with anti-PD-1, PD-L1, anti-CTLA-4, or therapies specifically targeting T-cell co-stimulation were excluded from this trial ( except for melanoma subjects where prior first-line anti-CTLA-4 was permitted ). ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Annual Meeting, 2017