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Hi, I'm Dr. Omid Hamid. I'm the director of translational research and immuno-oncology at the Angeles Clinic and Research Institute in Los Angeles, California. Today I'll be discussing my oral presentation of epicadostat, plus pembrolizumab in squamous cell carcinoma of the head and neck. This is ECHO-202/KEYNOTE-037 study, a phase one and two study of the combination of epicadostat plus pembrolizumab. Patients with metastatic or recurrent squamous cell carcinoma of the head and neck have a poor prognosis. Conventional second line therapy is associated with only a 3% to 6% response rate and an overall survival of approximately five to six months.
The introduction of immune checkpoint inhibitors has provided new therapeutic options, single agent pembrolizumab in the second line setting post platinum failure has shown response rates of 16% to 18% per keynote 55 and keynote 12. These data are encouraging and combination therapy was then initiated. IDO inhibitors like epicadostat have come through knowing that tumors can evade immuno surveillance through a number of mechanisms including immune checkpoint blockade and up-regulation of the IDO1 enzyme. This is an interferon gamma induced intracellular enzyme that catalyzes the first and rate-limiting step of tryptophan degradation and the kynurenine pathway.
This leads to immune suppression in the tumor micro-environment, so it's postulated that treatment strategies that combine epicadostat with checkpoint inhibitors can improve patient outcome. KEYNOTE-202 was a phase 1b phase two study looking at dose escalation as epicadostat plus pembrolizumab. Initially pembrolizumab two milligrams per kilogram and then in the expansions, a set 200 milligram every three week dose with a phase two open label cohort expansion which included squamous cell carcinoma of the head and neck. The objective here is to report the safety and tolerability. Patients who are greater than 18 years of age had confirmed metastatic or recurrent squamous cell carcinoma of the head and neck excluding nasopharyngeal and salivary gland and they would have had to have at least one prior systemic chemotherapy regimen including platinum-based therapy.
The demographics are shown here with most patients having more than one line of therapy, HPV status is here with 34% HPV associated and 63 non-HPV associated. PD-L1 expression was based on tumor and immune cell PD-L1 expression with positivity being greater than 1%. Here you can see the objective response rate by resist 1.1 of all comer patients with a response rate of 38 patients of 34% and a disease control rate or 61%. When you look at number of lines of therapy a greater response rate in one to two lines of therapy as compared to greater than or equal to three lines of therapy, although the numbers are small here and a better disease control.
PD-L1 expression shows no clear bias and an equal disease control rate with these numbers of patients. As previously reported, a higher associated response rate with HPV associated squamous cell carcinoma of the head and neck, but a disease control rate that was similar. You can see in these waterfalls and spider plots that disease response was rapid, deep and durable in all types of patients including those with one to two or greater than three lines of therapy including those with low and high PD-L expression and also including HPV associated and non-associated disease. Treatment-related adverse events is important here. As you can see treatment-related adverse events were low, grade three and four, 18%, mainly fatigue, diarrhea, and amylase increase. Dose interruptions in 18% of patients, the most common fatigue and dizziness. One patient had a dose reduction due to treatment-related adverse event. One discontinued treatment to asymptomatic grade three amylase increase and lipase increase, which are manageable. There was one treatment-related death due to respiratory failure. Pneumonitis did not be ruled out.
AEs of special interest were hypothyroidism, adrenal insufficiency and pneumonitis with no grade three or four adverse event of special interest. In conclusion, these phase one two study results show that epicadostat plus pembrolizumab is active in patients with metastatic or recurrent squamous cell carcinoma of head and neck. The overall response rate was 39% in patients with one to two prior lines of therapy and disease control 65%. Responses were seen regardless of PD-L1 expression, HPV status and number of lines of therapy. Out of the 13 responses, 10 were ongoing with a median range of duration of 18.4 weeks and up to 90.3 weeks.
This combination was well tolerated. The safety profile was consistent with previously reported phase one findings as well as the phase one and two safety data in other tumor types and the polled phase two safety data from this study which has been presented at this ASCO. In general the AEs of special interest with this combination were similar to pembrolizumab monotherapy. The frequency of grade three and four rash was higher with this combination. The efficacy of this combination in squamous cell carcinoma head and neck patients was consistent with findings in patients with other tumor types supporting an upcoming phase three investigation of this combination in squamous cell carcinoma of the head and neck. As you can see, this data is significantly hypothesis generating and does support a randomized phase three study that will be accruing. Thank you for your attention and time.