LBA68 Bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) compared to the investigator’s choice of sunitinib or cabozantinib in previously untreated advanced renal cell carcinoma (RCC): Results from a phase III randomized study (PIVOT-09)

Tannir, N.; Formiga, M.N.; Agarwal, N.; Pal, S.K.; Cho, D.; George, D.J.; Hong, W.; Tang, Liang-Ke; Qureshi, A.; Tagliaferri, M.A.; Zalevsky, J.; Penkov, K.D.

doi:10.1016/j.annonc.2022.08.073

Cited by 10 publications

(4 citation statements)

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“…This is exactly what had happened with high-dose interleukin-2 (IL-2) not too long ago, when <10% of patients with metastatic melanoma experienced a durable complete response [60]. Unfortunately, recent efforts to revive an engineered IL-2 pathway agonist (NKTR-214 or bempegaldesleukin) in patients with untreated RCC or urothelial carcinoma have also been rather unsatisfactory or outright disappointing [26].…”

Section: Cpis Are Not Equal (Which?)mentioning

confidence: 98%

Stem Cell Origin of Cancer: Clinical Implications for Cancer Immunity and Immunotherapy

Tu,

Aydin,

Maraboyina

et al. 2023

Cancers

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A simple way to understand the immune system is to separate the self from non-self. If it is self, the immune system tolerates and spares. If it is non-self, the immune system attacks and destroys. Consequently, if cancer has a stem cell origin and is a stem cell disease, we have a serious problem and a major dilemma with immunotherapy. Because many refractory cancers are more self than non-self, immunotherapy may become an uphill battle and pyrrhic victory in cancer care. In this article, we elucidate cancer immunity. We demonstrate for whom, with what, as well as when and how to apply immunotherapy in cancer care. We illustrate that a stem cell theory of cancer affects our perspectives and narratives of cancer. Without a pertinent theory about cancer’s origin and nature, we may unwittingly perform misdirected cancer research and prescribe misguided cancer treatments. In the ongoing saga of immunotherapy, we are at a critical juncture. Because of the allure and promises of immunotherapy, we will be treating more patients not immediately threatened by their cancer. They may have more to lose than to gain, if we have a misconception and if we are on a wrong mission with immunotherapy. According to the stem cell theory of cancer, we should be careful with immunotherapy. When we do not know or realize that cancer originates from a stem cell and has stem-ness capabilities, we may cause more harm than good in some patients and fail to separate the truth from the myth about immunotherapy in cancer care.

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Section: Cpis Are Not Equal (Which?)mentioning

confidence: 98%

Stem Cell Origin of Cancer: Clinical Implications for Cancer Immunity and Immunotherapy

Tu,

Aydin,

Maraboyina

et al. 2023

Cancers

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“…Grade ≥3 TRAEs occurred in 83 patients (26.8%), and 24 patients (7.7%) discontinued bempegaldesleukin plus nivolumab due to TRAEs. Grade 5 TRAEs occurred in 3 out of 310 patients (1.0%) [29].…”

Section: Bempegaldesleukinmentioning

confidence: 99%

Rethinking Oncologic Treatment Strategies with Interleukin-2

Takebe

Andrews

et al. 2023

Cells

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High-dose recombinant human IL-2 (rhIL-2, aldesleukin) emerged as an important treatment option for selected patients with metastatic melanoma and metastatic renal cell carcinoma, producing durable and long-lasting antitumor responses in a small fraction of patients and heralding the potential of cancer immunotherapy. However, the adoption of high-dose rhIL-2 has been restricted by its severe treatment-related adverse event (TRAE) profile, which necessitates highly experienced clinical providers familiar with rhIL-2 administration and readily accessible critical care medicine support. Given the comparatively wide-ranging successes of immune checkpoint inhibitors and chimeric antigen receptor T cell therapies, there have been concerted efforts to significantly improve the efficacy and toxicities of IL-2-based immunotherapeutic approaches. In this review, we highlight novel drug development strategies, including biochemical modifications and engineered IL-2 variants, to expand the narrow therapeutic window of IL-2 by leveraging downstream activation of the IL-2 receptor to selectively expand anti-tumor CD8-positive T cells and natural killer cells. These modified IL-2 cytokines improve single-agent activity in solid tumor malignancies beyond the established United States Food and Drug Administration (FDA) indications of metastatic melanoma and renal cell carcinoma, and may also be safer in rational combinations with established treatment modalities, including anti-PD-(L)1 and anti-CTLA-4 immunotherapy, chemotherapies, and targeted therapy approaches.

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“…The phase 3 PIVOT-09 study unexpectedly failed to improve the likelihood of response or OS with nivolumab combined with an engineered IL-2 pathway agonist (bempegaldesleukin), compared with a control TKI in patients with untreated renal cell carcinoma (RCC) [ 61 ]. This is noteworthy because PIVOT-09 was widely expected to be a positive study based on prior phase 1/2 results.…”

Section: Immune Activation/modulationmentioning

confidence: 99%

Stem Cell Origin of Cancer: Clinical Implications beyond Immunotherapy for Drug versus Therapy Development in Cancer Care

Tu,

Trikannad,

Vellanki

et al. 2024

Cancers

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Although immunotherapy has revolutionized cancer care, there is still an urgent need to enhance its efficacy and ensure its safety. A correct cancer theory and proper scientific method empower pertinent cancer research and enable effective and efficient drug versus therapy development for patient care. In this perspective, we revisit the concept of immune privilege in a cancer cell versus normal cell, as well as in a cancer stem cell versus normal stem cell. We re-examine whether effective immunotherapies are efficacious due to their anti-cancer and/or immune modulatory mechanisms. We reassess why checkpoint inhibitors (CPIs) are not equal. We reconsider whether one can attribute the utility of immunotherapy to specific cancer subtypes and its futility to certain tumor/immune compartments, components, and microenvironments. We propose ways and means to advance immunotherapy beyond CPIs by combining anti-PD1/L1 with various other treatment modalities according to an appropriate scientific theory, e.g., stem cell origin of cancer, and based on available clinical evidence, e.g., randomized clinical trials. We predict that a stem cell theory of cancer will facilitate the design of better and safer immunotherapy with improved selection of its use for the right patient with the right cancer type at the right time to optimize clinical benefits and minimize potential toxic effects and complications.

show abstract

LBA68 Bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) compared to the investigator’s choice of sunitinib or cabozantinib in previously untreated advanced renal cell carcinoma (RCC): Results from a phase III randomized study (PIVOT-09)

Cited by 10 publications

References 0 publications

Stem Cell Origin of Cancer: Clinical Implications for Cancer Immunity and Immunotherapy

Stem Cell Origin of Cancer: Clinical Implications for Cancer Immunity and Immunotherapy

Rethinking Oncologic Treatment Strategies with Interleukin-2

Stem Cell Origin of Cancer: Clinical Implications beyond Immunotherapy for Drug versus Therapy Development in Cancer Care

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