{"entity":{"id":"bempegaldesleukin","kind":"drug","name":"Bempegaldesleukin","aka":[],"tldr":"Bempegaldesleukin was a re-engineered interleukin-2 meant to be a safer version of a famous old immunotherapy. It added nothing to nivolumab in three phase 3 trials.","summary":"Bempegaldesleukin is a PEGylated IL-2 prodrug biased toward the CD122 receptor to expand CD8 T cells over regulatory T cells. Phase 1/2 PIVOT-02 with nivolumab reported high response rates in melanoma. In 2022, PIVOT IO-001 (melanoma), PIVOT-09 (RCC), and PIVOT-10 (urothelial) all failed to improve response, PFS, or OS over nivolumab alone; BMS and Nektar ended the collaboration (BMS had paid $1.85B upfront in 2018).\n\nLesson: single-arm combination response rates in melanoma are unreliable because nivolumab alone already produces them; biological rationale (Treg sparing) did not translate.","status":"negative","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Bempegaldesleukin","links":[{"label":"PIVOT IO-001 (J Clin Oncol 2023)","url":"https://ascopubs.org/doi/10.1200/JCO.23.00172"}],"tags":["failure","lesson:phase-2-mirage"],"related":[],"cancers":["melanoma","rcc","urothelial"],"sections":[],"technologies":["cytokine-therapy"],"targets":[],"drugs":["nivolumab"],"companies":["bms","nektar-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":["nct03635983","nct04410445","nct03729245"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"NKTR-214, bempeg","modality":"Engineered cytokine (PEGylated IL-2)","mechanism":"IL-2 with releasable PEG chains; preferential CD122 (IL-2Rβγ) engagement.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/bempegaldesleukin/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"cytokine-therapy","kind":"technology","name":"Cytokines & engineered cytokines","route":"/technologies/cytokine-therapy/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"},{"id":"nektar-therapeutics","kind":"company","name":"Nektar Therapeutics","route":"/companies/nektar-therapeutics/"}],"trial":[{"id":"nct03729245","kind":"trial","name":"A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)","route":"/trials/nct03729245/"},{"id":"nct03635983","kind":"trial","name":"A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma","route":"/trials/nct03635983/"},{"id":"nct04410445","kind":"trial","name":"Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence","route":"/trials/nct04410445/"}],"bottleneck":[{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"}],"pathway":[{"id":"t-cell-exhaustion","kind":"pathway","name":"T-cell exhaustion","route":"/pathways/t-cell-exhaustion/"}],"target":[{"id":"il2rb","kind":"target","name":"IL2RB","route":"/targets/il2rb/"}]}}