On May 22, 2020 Nektar Therapeutics (Nasdaq: NKTR) reported the publication of Phase 1 clinical data for its lead immuno-oncology candidate, bempegaldesleukin (BEMPEG: NKTR-214) in combination with nivolumab, in Cancer Discovery, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Nektar Therapeutics, MAY 22, 2020, View Source [SID1234558423]). Previously published Phase 1 data in Cancer Discovery on BEMPEG, a CD122-preferential IL-2 pathway agonist, demonstrated that when administered as a monotherapy, it was well tolerated and showed clinical activity, including tumor shrinkage and durable disease stabilization, in heavily pretreated patients with solid tumor cancers.1 The manuscript published today presents the safety, immune-activation and efficacy results from a Phase 1 dose-escalation study conducted in 38 patients with immunotherapy-naïve, advanced solid tumors, including melanoma, renal cell carcinoma (RCC), and non-small cell lung cancer (NSCLC).
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This manuscript, entitled "Bempegaldesleukin (NKTR-214) Plus Nivolumab in Patients With Advanced Solid Tumors: Phase 1 Dose-Escalation Study of Safety, Efficacy & Immune Activation (PIVOT-02)," is published online and can be accessed here View Source
Dr. Adi Diab, lead author, Associate Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center noted: "Our data show that BEMPEG, in combination with nivolumab, increases T-cell infiltration into the tumor microenvironment and increases PD-L1 expression on-treatment, leading to very encouraging response rates. Of equal importance, our data did not show an increase in the inflammatory T-cell subtype Th-17, which is known to play a crucial role in mediating the typical checkpoint inhibitor immune-related adverse events. In other words, BEMPEG in combination with nivolumab is well tolerated and induces meaningful tumor and immune responses in solid tumors, such as melanoma, RCC, and NSCLC."
Dr. Daniel C. Cho, Associate Professor at NYU Grossman School of Medicine, Phase 1 clinical trial director at NYU Langone Health’s Perlmutter Cancer Center, one of the co-senior authors on the study, added: "While checkpoint inhibitors are effective in several tumor types, only a subset of patients derive durable response; the combination of BEMPEG plus nivolumab not only demonstrated encouraging clinical activity irrespective of baseline PD-L1 status, across tumor types, but it also deepened with additional cycles of treatment and in many cases is maintained off treatment."
Key findings are summarized below:
Established the recommended Phase 2 dose (RP2D) of BEMPEG 0.006 mg/kg q3w plus nivolumab 360 mg q3w
AEs were manageable and generally transient and reversible
Combination of BEMPEG plus nivolumab increased absolute numbers and proliferation of CD8+ T- and NK cells in the peripheral blood, and increased expression of genes relating to immune activation in the tumor microenvironment, including the genes encoding the interferon gamma inflammatory response to PD-L1
BEMPEG plus nivolumab demonstrated encouraging ORRs across multiple tumor types, independent of baseline PD-L1 expression. These responses continued to deepen over time
Total ORR was 59.5%, CR was 18.9%, and DCR 83.8%
ORR in PD-L1+ and PD-L1- patients was respectively 64.7% and 50.0%
Among the 22 patients with confirmed objective responses, median TTR was 1.9 months (range 1.3-7.8) and median DOR was not reached
"These PIVOT-02 data further demonstrate the scientific and clinical rationale for combining BEMPEG with nivolumab for a range of advanced solid tumors. We are excited that this combination is now being developed in several ongoing Phase 2 and 3 registration trials. We look forward to the continued development of this promising combination treatment regimen," remarked Dr. Jonathan Zalevsky, Chief Research & Development Officer of Nektar Therapeutics.
BEMPEG in combination with nivolumab is being evaluated in multiple clinical trials including metastatic melanoma (NCT03635983), muscle-invasive bladder cancer (NCT04209114), metastatic cis-ineligible urothelial cancer (NCT03785925) and metastatic renal cell carcinoma (NCT03729245).