Unfortunately, the majority of patients with UC do not have an elevated PD-L1 expression, and many patients in the front line are also cisplatin in-eligible due to renal impairment, hearing loss, peripheral neuropathy, or poor performance status. Thus, additional therapies are necessary for this vulnerable population of patients. This study evaluates NKTR-214, a CD122-preferential IL-2 pathway agonist for patients with mUC.
This is an interim analysis of PIVOT-2, a multicenter phase 1/2 study of NKTR-214 for patients with locally advanced or metastatic UC who are either cisplatin-ineligible or have declined cisplatin based chemotherapy. The data cutoff point at the time of this analysis is December 3rd, which provides a median duration of follow up of 5.1 months.
A total of 41 patients with UC have been enrolled and 27 patients are available for follow up at this time. The median age of this population was 70. 75% of patients were ineligible due to poor renal function. Most patients had not had cystectomy (93%). 41% of patients were classified as PD-L1 negative based on a TC<1%. 56% of patients had visceral disease.
In terms of safety, 88% of patients had a treatment related adverse event. The most common low grade (1/2) events were flu like symptoms, fatigue, rash, and pruritus. The most common grade 3 or 4 events were also flu like symptoms and hypotension. One patient developed complete AV block and one patient developed myocarditis. No patients had grade 4 or 5 toxicity. 10% of patients discontinued treatment due to adverse events.
In terms of efficacy, the objective response rate was 48%, with 19% complete responses and 30% partial responses. There was no significant difference in the objective response rate between PD-L1 negative and PD-L1 positive tumors. There are also 4 additional unconfirmed responses and 1 additional unconfirmed complete response. 10 patients are still pending their first scan. 85% of patients have ongoing responses and amongst patients who have a response, no patients have discontinued due to relapse.
In terms of biomarker analysis, 13 patients had pre treatment and post treatment biopsies. 70% of PD-L1 negative tumors had been converted to PD-L1 positive tumors. Responses were also seen independent of baseline CD8 T cell infiltration.
This phase I/II study shows that NKTR-214 in combination with nivolumab is highly active for cisplatin ineligible patients with urothelial carcinoma. NKTR-214 successfully converted 7/10 PD-L1 negative tumors to PD-L1 positive based on the PharmDx 28-8 assay. A recent study examine the concordance of PD-L1 expression between primary and metastatic UC lesions and found that PD-L1 expression is temporally and spatially discordant so this may confound some of the PD-L1 data (CITE). Nonetheless, this abstract provides very exciting efficacy data, especially with the 20% complete response rate which is unheard of in this space. The main limitations of this study is the size and limited follow up but a larger phase II study is underway.
Presented by: Arlene O. Siefker-Radtke, MD, Department of Genitourinary Medical Oncology, Division of Cancer Medicine MD Anderson Cancer Center
Written by: Jason Zhu,MD, Fellow, Division of Hematology and Oncology, Duke University. Twitter: @TheRealJasonZhu at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA
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