Nektar Therapeutics Presents Biomarker and Clinical Data from PIVOT-02 Phase 2 Study of Bempegaldesleukin with Nivolumab at 2019 ASCO Annual Meeting

On June 1, 2019 Nektar Therapeutics (Nasdaq: NKTR) reported that biomarker and clinical data from PIVOT-02 is being presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Meeting in Chicago, Illinois (Press release, Nektar Therapeutics, JUN 1, 2019, View Source [SID1234536786]).

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New baseline biomarker analyses and updated clinical study efficacy and safety results were shared in a presentation titled, "Baseline tumor-immune signatures associated with response to bempegaldesleukin (NKTR-214) and nivolumab" (Abstract #2623/Poster Board #267) by Michael Hurwitz, Ph.D., M.D. who serves as Assistant Professor of Medicine, Medical Oncology at Yale Cancer Center during the "Developmental Immunotherapy and Tumor Immunobiology" poster session on Saturday, June 1, 2019.

"The Stage IV melanoma patients enrolled in the ongoing PIVOT-02 study continue to experience both deepening and durability of response over time," said Jonathan Zalevsky, Ph.D., Chief Scientific Officer at Nektar Therapeutics. "This translated into a 34% rate of complete response at a 12-month follow-up for the 38 efficacy-evaluable patients in this cohort. Further, 42% of patients achieved a 100% reduction in target lesions. Finally, corresponding lymphocyte data highlight the benefit of replenishing and stimulating T cells continuously over the course of treatment with an I-O doublet regimen."

Bempegaldesleukin (NKTR-214, bempeg) is an investigational, CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 beta-gamma receptor. PIVOT-02 is an ongoing Phase 2 study evaluating bempeg in combination with nivolumab in solid tumors.

Highlights from the biomarker, clinical efficacy and safety data presented at ASCO (Free ASCO Whitepaper) 2019 are provided below:

Biomarkers and Mechanism of Action:

Exploratory biomarker analyses of PIVOT-02 baseline tumor biopsies identified immune signatures that potentially enrich for response in patients with 1L metastatic melanoma and not 1L metastatic urothelial carcinoma.
Notable response rates were seen in both 1L metastatic melanoma and 1L metastatic urothelial cancer patients (ASCO 2019 and ASCO (Free ASCO Whitepaper)-GU 2019), regardless of PD-L1 status or unfavorable tumor microenvironments.
12 Month Follow-Up for 1L Melanoma Cohort in PIVOT-02:
(Response measured by RECIST 1.1 by independent central radiology review for 38 efficacy-evaluable patients per protocol which were treated at the recommended Phase 2 dose in PIVOT-02 and with >1 on treatment scan. Data cut as of March 29, 2019):

At a median time of follow-up of 12.7 months, confirmed objective response rate (ORR) was 53% (20/38) in efficacy-evaluable patients, with 34% (13/38) of patients achieving confirmed complete responses. 42% (16/38) of patients achieved a maximum reduction of 100% in target lesions. DCR, also known as disease control rate (CR+ PR + SD) was 74%.
Median time to response was 2 months. Median duration of response was not reached. At the 12.7 month median follow-up, data were too immature to calculate median progression-free survival (PFS).
80% (16/20) of patients with responses have ongoing responses. Amongst the 35 patients with known pre-treatment PD-L1 status, ORR in PD-L1 negative patients was 6/14 (43%) and in PD-L1 positive patients was 13/21 (62%). One of three patients with unknown PD-L1 baseline status experienced a CR.
The most common (>30%) treatment-related adverse events (TRAEs) were grade 1-2 fatigue (65.9%), pyrexia (61.0%), rash (56.1%), pruritus (48.8%), nausea (41.5%), influenza like illness (39.0%), arthralgia (36.6%), chills (34.1%) and myalgia (31.7%). A total of 6/41 (14.6%) of patients experienced a Grade 3 (G3) or higher TRAE with 4/41 (9.8%) patients discontinuing treatment due to a TRAE. A total of 41 patients have been treated at the RP2D with 3 patients discontinuing prior to 1st scan due to an unrelated treatment-emergent adverse event (n=1) and patient decision (n=2).
A Phase 3 trial evaluating bempeg in combination with nivolumab versus nivolumab in first-line advanced melanoma patients is currently recruiting patients (NCT03635983). A Phase 2 pivotal trial evaluating bempeg in combination with nivolumab in first-line metastatic urothelial cancer is currently recruiting patients (NCT03785925).

Details of the poster presentation are provided below and a link to a copy of the poster presentation is available on Nektar’s corporate website: View Source

Abstract #2623/Poster Board #267
Title: "Baseline tumor-immune signatures associated with response to bempegaldesleukin (NKTR-214) and nivolumab", Hurwitz, M., et al.
Date: Saturday, June 1, 2019, 8:00 a.m. – 11:00 a.m. Central Time
Location: McCormick Place, Exhibit Hall A