SAN FRANCISCO, May 22, 2020 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced 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. 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).
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 https://cancerdiscovery.aacrjournals.org/content/early/2020/05/20/2159-8290.CD-19-1510
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).
Nektar Therapeutics is a biopharmaceutical company with a robust, wholly owned R&D pipeline of investigational medicines in oncology and immunology as well as a portfolio of approved partnered medicines. Nektar is headquartered in San Francisco, California, with additional operations in Huntsville, Alabama and Hyderabad, India. Further information about the company and its drug development programs and capabilities may be found online at http://www.nektar.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements which can be identified by words such as: "may," "can," "develop," "continue," "maintain," and similar references to future periods. Examples of forward-looking statements include, among others, statements we make concerning the therapeutic potential of bempegaldesleukin ("BEMPEG"), the maintenance and deepening of responses following the administration of BEMPEG in combination with nivolumab, and our future development plans for BEMPEG. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) the extent and duration of the impact of the COVID-19 pandemic on our business, regulatory efforts, research and development, clinical trials (including those being led by us and our partners), and corporate development activities will depend on future developments that are highly uncertain and cannot be accurately predicted, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the U.S. and in other countries, as well as the effectiveness of actions taken globally to contain and treat the disease; (ii) BEMPEG is an investigational agent and continued research and development for this drug candidate is subject to substantial risks, including negative safety and efficacy findings in ongoing clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, competitive factors, or delay or failure in ultimately obtaining regulatory approval in one or more important markets; (iv) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (v) certain other important risks and uncertainties set forth in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 8, 2020. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
Vivian Wu of Nektar Therapeutics
Dan Budwick of 1AB
1Bentebibel, S.E.; Hurwitz, M.E.; Bernatchez, C.; Haymaker, C.; Hudgens, C.W.; Kluger, H.M.; Tetzlaff, M.T.; Tagliaferri, M.A.; Zalevsky, J.; Hoch, U.; et al. A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rbetagamma-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors. Cancer Discov. 2019, 9, 711–721.
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