Bempegaldesleukin (BEMPEG/NKTR-214)
Bempegaldesleukin (BEMPEG/NKTR-214), Nektar's Lead Immuno-oncology Candidate
Bempegaldesleukin (BEMPEG/NKTR-214) is an immunostimulatory IL-2 cytokine prodrug which has been engineered to deliver a controlled, sustained, and preferential IL-2 pathway signal.
BEMPEG works by stimulating and expanding specific cancer-killing T-cells and natural killer (NK) cells without expanding intratumoral regulatory T cells, which dampen the immune response.
Bristol Myers Squibb and Nektar are actively advancing five registrational programs and one mid-stage program for BEMPEG in combination with nivolumab (OPDIVO®). The combination of BEMPEG and nivolumab leverages two clinically validated complementary IO pathways to unleash the full effect of the immune system against cancer.
BEMPEG is also being developed in partnership with Merck and SFJ Pharmaceuticals in a Phase 2/3 study in patients with metastatic head and neck cancer whose tumors express PD-L1.
Additional clinical studies evaluating BEMPEG in combination with other agents, such as cancer vaccines, are also underway. BEMPEG is also being evaluated as a potential treatment for mild COVID-19.
Pipeline
*Planned registrational study
References
1. Boyman, J., et al., Nature Reviews Immunology, 2012, 12, 180-190.
2. Charych, D., et al., Clin Can Res; 22(3) February 1, 2016
3. Diab, A., et al., Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):P369
2021 Journal of Clinical Oncology
2021 Journal for ImmunoTherapy of Cancer
2021 World Congress of Melanoma (WCM)
- Poster P-042: “Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study”, A. Diab, et al.
- TiP Poster P-047: “PIVOT-12: a Phase 3 randomized study of adjuvant bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) versus NIVO in completely resected cutaneous melanoma at high risk for recurrence”, A. Eggermont, et al.
2021 Annual Reviews
2020 World Conference on Lung Cancer Singapore
- Presentation: P77.04 (Trials in progress (TiP) poster): "PROPEL: A phase 1/2 trial of bempegaldesleukin (BEMPEG; NKTR-214) plus pembrolizumab in lung cancer and other advanced solid tumours)", D.R. Spigel, et al.
2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting
- Presentation: Progression-free Survival and Biomarker Correlates of Response With BEMPEG Plus NIVO in Previously Untreated Patients With Metastatic Melanoma: Results From The PIVOT-02 Study
- Presentation: Phase 1 Dose-Escalation Study of NKTR-262, a Novel TLR7/8 Agonist, Plus Bempegaldesleukin: Local Innate Immune Activation and Systemic Adaptive Immune Expansion for Treating Solid Tumors
- Abstract 451: "Combining Bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) pairs local innate activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity", Rolig, A., et al.Oral presentation/Abstract #28
2020 Cancer Discovery
2020 Future Medicine
- Publication: PIVOT-10: Design and rationale for the phase 2, single-arm PIVOT-10 study of bempegaldesleukin in combination with nivolumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (NCT03785925).
- Publication: PIVOT IO 001 (Mel): Design and rationale for the randomized, open-label, Phase 3 PIVOT IO 001 study of bempegaldesleukin, a first-in-class CD122-preferential IL-2 pathway agonist, plus nivolumab versus nivolumab monotherapy in patients with previously untreated, unresectable, or metastatic melanoma (NCT03635983).
2020 Genitourinary Cancers Symposium
- Abstract TPS589: “PIVOT-10: A phase II study of bempegaldesleukin (NKTR-214) in combination with nivolumab (NIVO) in cisplatin (cis) ineligible patients with previously untreated locally advanced or metastatic urothelial cancer (mUC).”
- Abstract TPS763: “PIVOT-09: A phase III randomized open-label study of bempegaldesleukin (NKTR-214) plus nivolumab versus sunitinib or cabozantinib (investigator’s choice) in patients with previously untreated advanced renal cell carcinoma (RCC).”
Nature Communications – January 31, 2020
- Manuscript: “Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy”
- Manuscript: “Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist”
Kidney Cancer Journal
ESMO Immuno-Oncology Congress 2019
- TiP Poster 127TiP: "PROPEL: A phase I/II trial of bempegaldesleukin (NKTR-214) in combination with pembrolizumab (pembro) in patients (pts) with advanced solid tumours,” Schwarz, J., et al.
2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting
- Abstract P623: "Bempegaldesleukin in combination with local radiation and systemic checkpoint blockade induces a robust systemic anti-tumor immunity", Pieper, A., et al.
- Abstract P387: "(Trials in Progress): "A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and Immunotherapy Combinations for the Treatment of Patients with Metastatic Castration-resistant Prostate Cancer (PORTER)", Nissola, L., et al
- Oral Abstract O35: "Clinical activity, including deepening of response, of BEMPEG plus NIVO in previously untreated patients with metastatic 1L Melanoma: results from the Phase 1/2 PIVOT-02 Study"
Fifth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
2019 ASCO Annual Meeting
- Abstract #2623/Poster Board #267: "Baseline tumor-immune signatures associated with response to bempegaldesleukin (NKTR-214) and nivolumab", Hurwitz, M., et al.
- Abstract #2584/Poster Board #228: "Overcoming genetically-based resistance mechanisms to PD-1 blockade", Torrejon, D., et al.
- Abstract #11010: "Pilot study of bempegaldesleukin (NKTR-214) and nivolumab in patients with sarcomas", D’Angelo, S., et al.
- Abstract TPS9601/Poster Board #168b (Trials in progress (TiP) abstract): "CA045-001: A phase III, randomized, open label study of bempegaldesleukin (NKTR-214) plus nivolumab (NIVO) versus NIVO monotherapy in patients (pts) with previously untreated, unresectable or metastatic melanoma (MEL)", Khushalani, N., et al.
- Abstract TPS4595/Poster Board #416b (Trials in progress (TiP) abstract): "A phase III randomized open label study comparing bempegaldesleukin (NKTR-214) plus nivolumab to sunitinib or cabozantinib (investigator's choice) in patients with previously untreated advanced renal cell carcinoma", Tannir, N., et al.
Cancer Discovery
- A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors
AACR 2019
- Abstract 3210/Poster Board 20: “A potential immunotherapeutic approach for the treatment of osteosarcoma”, Wahba, A., et al.
- Abstract 2256/Poster Board 15: “Combination of neoantigen DNA plasmid vaccine VB10.NEO and NKTR-214, a CD122-biased immunostimulatory cytokine, induces strong neoantigen-specific T cell responses and sustained tumor regression in pre-clinical models”, Granum, S., et al.
2019 ASCO-SITC Clinical Immuno-Oncology Symposium
- Oral presentation/Abstract #28: “Phase Ib: Preliminary clinical activity and immune activation for NKTR-262 [TLR 7/8 agonist] plus NKTR-214 [CD122-biased agonist] in patients (pts) with locally advanced or metastatic solid tumors (REVEAL Phase Ib/II Trial).”, Diab, A.
2019 Genitourinary Cancers Symposium (ASCO-GU)
SITC 2018
- Oral Abstract #O4: "Immune monitoring after NKTR-214 plus nivolumab (PIVOT-02) in previously untreated patients with metastatic Stage IV melanoma,", Diab, A., et al.
- Abstract #P424: "NKTR-214, an engineered IL-2, selectively depletes intratumoral Tregs and expands immunotherapy-induced effector T cell responses", Sharma, M., et al.
- Abstract #P368: "Combination of a Dipeptidyl Peptidase Inhibitor BXCL701 and Biased CD122 Agonist NKTR-214 with Anti-PD1 Provides Functional Immunological Memory through Inflammatory Cell Death", MacDougall, J., et al.
- Abstract #P348: "Survival and immune modulation in homologous recombination deficient murine ovarian tumors using the PARP inhibitor, rucaparib and immune agonist, NKTR-214", Charych, D., et al.
- Abstract #P419: "NKTR-214 in combination with radiation produces a potent in situ vaccine in the syngeneic B78 melanoma model", Sondel, P., et al.
- Abstract #P557: "Overcoming genetically-based resistance mechanisms to PD-1 blockade", Torrejon, D., et al.
- Abstract #P364: "Systemic anti-tumor immunity and immune memory formation by a novel TLR7/8 targeting agent NKTR-262 combined with CD122-biased immunostimulatory cytokine NKTR-214", Kivimae, S., et al.
- Abstract #P378: "NKTR-214 (CD122-biased agonist) and NKTR-262 (TLR7/8 agonist) combination treatment pairs local innate immune activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity", Rolig, A., et al.
2018 ESMO Congress
2018 American Conference on Pharmacometrics (ACoP), San Diego, CA
- Poster W-019: "Mechanistic modeling of receptor pharmacology of NKTR-214, a new kinetically-controlled CD122 agonist for cancer immunotherapy"
SMI Immuno-Oncology Conference, London, UK
2018 ASCO Annual Meeting
- Oral Abstract 3006: “Bempegaldesleukin (NKTR-214) + nivolumab in first-line advanced/metastatic urothelial carcinoma (mUC): Updated results from PIVOT-02”, Siefker-Radtke, A., et al.
- Abstract #3085/ Poster Board #299: "Efficacy and immune modulation by BXCL701 a dipeptidyl peptidase inhibitor, NKTR-214 a CD122-biased immune agonist with PD1 blockade in murine pancreatic tumors", Rastelli, L., et al.
- Abstract #2567/Poster Board #393: "TAK-659 in Combination with NKTR-214 and anti-PD-1 Therapy Leads to Complete and Sustained Tumor Regression and Immune Memory In Pre-Clinical Syngeneic Models", Huck, J., et al.
- Abstract #TPS3115/Poster Board #322a: "PROPEL: A phase 1/2 trial of NKTR-214 (CD122-biased agonist) combined with anti-PD-1 (pembrolizumab) or anti-PD-L1 (atezolizumab) in patients (pts) with advanced solid tumors", Vaena, D., et al.
- Abstract #5582/Poster Board #309: "Efficacy and immune modulation of the tumor microenvironment in murine ovarian tumor with the PARP inhibitor rucaparib and CD122-biased immune agonist NKTR-214", Simmons, A., et al.
2018 American Association for Cancer Research (AACR) Annual Meeting
- Abstract 123/Poster 13: Enhanced anti-tumor activity of the combination of entinostat and NKTR-214 in renal and colon cancer tumor models”
- Abstract 3566/Poster 4: “Enhanced expansion and tumor targeting of adoptively transferred T cells with NKTR-214”
- Abstract 3755/Poster 5: “Comprehensive antitumor immune activation by a novel TLR7/8 targeting agent NKTR-262 combined with CD122-biased immunostimulatory cytokine NKTR-214”
- November 9, 2019: Nektar Therapeutics Presents New Clinical and Preclinical Data from its Immuno-Oncology Pipeline at the 2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting
- Sept 26, 2019: Clinical Data Presented from PIVOT-02 Study of Bempegaldesleukin (NKTR-214) with Nivolumab in Triple-Negative Breast Cancer Patients at the 2019 CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
- Aug 1, 2019: Nektar Therapeutics and Bristol-Myers Squibb Announce U.S. FDA Breakthrough Therapy Designation for Bempegaldesleukin (NKTR-214) in Combination with Opdivo® (nivolumab) for the Treatment of Patients with Untreated Advanced Melanoma
- Jun 1, 2019: Nektar Therapeutics Presents Biomarker and Clinical Data from PIVOT-02 Phase 2 Study of Bempegaldesleukin with Nivolumab at 2019 ASCO Annual Meeting
- Apr 2, 2019: Nektar Therapeutics Presents Preclinical Data on its Immuno-Oncology Pipeline Candidates at the American Association for Cancer Research (AACR) Annual Meeting 2019
- Apr 1, 2019: Vaccibody AS and Nektar Therapeutics Present New Preclinical Data from their Immuno-Oncology Collaboration at the American Association for Cancer Research (AACR) Annual Meeting 2019
- Mar 1, 2019: Nektar Therapeutics Presents Preliminary Immune Activation, Safety and Clinical Activity Data from the Ongoing Dose-Escalation Stage of the REVEAL Study at 2019 ASCO-SITC Meeting
- Feb 15, 2019: Clinical Data Presented from PIVOT-02 Study of Bempegaldesleukin (NKTR-214) with Nivolumab in Metastatic Urothelial Carcinoma Patients at the 2019 ASCO Genitourinary Cancers Symposium
- Nov 9, 2018: Nektar Therapeutics Presents New Clinical and Preclinical Data for its Immuno-Oncology Pipeline at the 2018 Society for Immunotherapy of Cancer (SITC) Annual Meeting
- Nov 6, 2018: New Clinical Oncology Collaboration Between Nektar and Pfizer to Evaluate Combination of NKTR-214, a CD122-Biased Agonist, with Avelumab and Talazoparib or Enzalutamide in Multiple Cancers
- June 2, 2018: Preliminary Data for NKTR-214 in Combination with Opdivo® (nivolumab) for Patients with Stage IV Metastatic Melanoma, Renal Cell Carcinoma, and Urothelial Cancers Presented at ASCO 2018
- May 30, 2018: Syndax and Nektar Therapeutics Announce Immuno-Oncology Clinical Trial Collaboration
- April 24, 2018: New Oncology Clinical Collaboration between Nektar and Takeda to Evaluate Combination of NKTR-214, a CD122-biased Agonist, and TAK-659, a Dual SYK and FLT-3 Inhibitor, in Liquid and Solid Tumors
- April 15, 2018: Nektar Therapeutics Presents New Preclinical Data for its Immuno-Oncology Programs at the American Association for Cancer Research (AACR) Annual Meeting 2018
- February 14, 2018: Bristol-Myers Squibb and Nektar Therapeutics Announce Global Development & Commercialization Collaboration for Nektar's CD122-biased Agonist, NKTR-214
- November 11, 2017: First Data for NKTR-214 in Combination with OPDIVO® (nivolumab) for Patients with Stage IV Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancers, Including Patients with PD-L1 Negative Status, Revealed at SITC 2017
- September 12, 2017: Nektar Therapeutics Initiates PROPEL Clinical Study to Evaluate Combination of NKTR-214, a CD122-Biased Agonist, with TECENTRIQ® (atezolizumab) or KEYTRUDA® (pembrolizumab)
- June 5, 2017: Nektar Presents New Clinical Data from Two Studies of NKTR-214, a CD122-Biased Agonist, at 2017 American Society of Clinical Oncology (ASCO) Annual Meeting
- May 22, 2017: New Research Collaboration between Nektar and Takeda to Explore Combination Cancer Therapy Approaches with NKTR-214, a CD122-Biased Agonist, and Five Takeda Cancer Therapy Compounds
- April 4, 2017: Nektar Therapeutics Presents New Preclinical Data for its Immuno-Oncology Programs at the American Association for Cancer Research (AACR) Annual Meeting
- February 18, 2017: Clinical Data from Phase 1 Dose-Escalation Study of Single-Agent NKTR-214 in Patients with Renal Cell Carcinoma Presented at the ASCO 2017 Genitourinary Cancers Symposium
- Nektar Therapeutics Presents New Clinical Data from Ongoing Phase 1 Dose-Escalation Study of NKTR-214 at the Society for Immunotherapy of Cancer (SITC) 2016 Annual Meeting
- Bristol-Myers Squibb and Nektar Therapeutics Announce Oncology Clinical Collaboration to Evaluate the Combination of Opdivo® (nivolumab) and NKTR-214
- June 6, 2016: Preclinical Data Presented at ASCO 2016 Annual Meeting Demonstrate that Single-Agent NKTR-214 Produces a Large Increase in Tumor-Infiltrating Lymphocytes to Provide Durable Anti-Tumor Activity
- April 18, 2016: Preclinical Data Presented at AACR Demonstrate that Combining NKTR-214 with Checkpoint Blockade is Superior to Dual Checkpoint Inhibition in Increasing Clonality of the T Cell Receptor (TCR) Repertoire and T Cell Tumor Infiltration
- February 1, 2016: Nektar Publishes Pre-clinical Results for NKTR-214, an Investigational CD122-Biased Immune-Stimulatory Cytokine for the Treatment of Cancer in Clinical Cancer Research
- December 8, 2015: Nektar Announces First Patient Dosed in Phase 1/2 Clinical Study of NKTR-214, a CD122-Biased Immuno-Stimulatory Cytokine
- June 2, 2015: Nektar and MD Anderson Cancer Center Announce Phase 1/2 Clinical Research Collaboration for NKTR-214, a CD122-Biased Immuno-Stimulatory Cytokine
- June 1, 2014: Nektar Presents Positive Preclinical Data for NKTR-214, a Novel Cancer Immunotherapy, at 50th ASCO Meeting
- April 9, 2014: Nektar Reports Positive Preclinical Data for Two Oncology Programs at 2014 AACR
- June 3, 2013: Nektar Presents Positive Preclinical Data for NKTR-214, a Novel Cancer Immunotherapy, At the 2013 American Society of Clinical Oncology Annual Meeting
- April 7, 2013: Positive Preclinical Data for NKTR-214, an Investigational Cancer Immunotherapy Targeting the IL-2 Receptor Complex, Presented at AACR Annual Meeting 2013
