bempegaldesleukin (NKTR-214) / Nektar Therapeutics, BMS, Ono Pharmaceutical - LARVOL DELTA

Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results. (PubMed, J Clin Oncol) - P3 | "The PIVOT IO 001 study did not meet its primary end points of ORR, PFS, and OS. Increased toxicity was observed with BEMPEG plus NIVO versus NIVO."

Journal • Metastases • P3 data • Melanoma • Oncology • Solid Tumor • IL2

PIVOT IO 001: First disclosure of efficacy and safety of bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) vs NIVO monotherapy in advanced melanoma (MEL) (ESMO 2022) - P3 | "Increased toxicity was observed with BEMPEG + NIVO vs NIVO. Ongoing biomarker analysis may help further interpret study results."

Clinical • IO biomarker • Monotherapy • Melanoma • Oncology • Solid Tumor • BRAF • IL2 • PD-L1

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) (ESMO 2022) - P3 | "Conclusions In pts with treatment-naïve advanced/metastatic clear-cell RCC, BEMPEG + NIVO did not improve outcomes vs investigator's choice of TKI. The combination's safety profile was consistent with previous reported findings."

Clinical • Late-breaking abstract • P3 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • IL2

Bempegaldesleukin Plus Nivolumab Versus Sunitinib or Cabozantinib in Previously Untreated Advanced Clear Cell Renal Cell Carcinoma: A Phase III Randomized Study (PIVOT-09). (PubMed, J Clin Oncol) - "First-line BEMPEG plus NIVO for advanced/metastatic ccRCC did not improve efficacy in patients with intermediate-/poor-risk disease but led to fewer grade 3/4 TRAEs versus TKI."

Journal • Metastases • P3 data • Clear Cell Renal Cell Carcinoma • Dermatology • Genito-urinary Cancer • Oncology • Pruritus • Renal Cell Carcinoma • Solid Tumor • IL2

A Prospective, Single-arm, Multicenter Exploratory Clinical Study of Anlotinib Combined With Bempegaldesleukin and Conventional Chemoradiotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Soft Tissue Sarcoma. (clinicaltrials.gov) - P2 | N=46 | Not yet recruiting | Sponsor: The First Affiliated Hospital with Nanjing Medical University

New P2 trial • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

A Single-Arm, Multicenter, Prospective Phase II Clinical Study of Anlotinib Hydrochloride Capsules Combined with Bempegaldesleukin as First-Line Treatment for Advanced Pheochromocytoma/Paraganglioma (ChiCTR) - P2 | N=22 | Not yet recruiting | Sponsor: Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

New P2 trial • Endocrine Cancer • Oncology • Solid Tumor

Clinical activity of immune checkpoint blockade in advanced perivascular epithelioid cell neoplasms (PEComas): A retrospective single center study. (ASCO 2025) - "While therapies targeting the mTOR pathway have shown promise, with nab-sirolimus being the first FDA-approved treatment for this histology, most patients will eventually progress...Most patients (78%) had previously received chemotherapy (gemcitabine and/or anthracycline, 54% each). ICIs included pembrolizumab (n = 5), nivolumab (n = 2), nivolumab-ipilimumab (n = 4), pembrolizumab-lenvatinib (n = 1) and nivolumab-bempegaldesleukin (n = 1)... The observed response rate of 23%, including two durable responses, suggests that ICIs may be an effective treatment option for a subset of PEComa patients, regardless of molecular profile. Further studies to identify predictive biomarkers and optimal sequencing with mTOR inhibitors and other therapies are warranted."

Checkpoint block • Checkpoint inhibition • IO biomarker • Metastases • Retrospective data • Gastrointestinal Disorder • Oncology • ATRX • FLT4 • NOTCH1 • RB1 • TFE3 • TP53 • TSC1 • TSC2

Efficacy of First-Line Treatments for Advanced Renal Cell Carcinoma: A Bayesian Network Meta-analysis of Objective Response, Progression-Free Survival, and Overall Survival. (PubMed, Target Oncol) - "The overall population analysis indicated that pembrolizumab + lenvatinib improves PFS and ORR compared with other approved ICI combination therapies in first-line aRCC. No significant differences in OS were observed between pembrolizumab + lenvatinib and other combination immune checkpoint inhibitor-based therapies."

Journal • Retrospective data • Review • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Study of NKTR-214 in Combination With Nivolumab in Patients With Metastatic and/or Locally Advanced Sarcoma (clinicaltrials.gov) - P2 | N=88 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Oncology • Sarcoma • Solid Tumor

Exploring the Dynamics of Immune Checkpoint Inhibitor-Induced Eosinophilia in Advanced/Metastatic Melanoma: A Comprehensive Retrospective Analysis. (PubMed, Cancer Med) - "This study marks the first comprehensive approach of the relationship between the type of immunotherapy and the incidence of eosinophilia in melanoma patients. It also delves into the patients' baseline characteristics, diagnostic assessment, management, and prognosis, providing useful guidance for physicians treating patients with ICIs."

Checkpoint inhibition • IO biomarker • Journal • Retrospective data • Eosinophilia • Melanoma • Oncology • Solid Tumor • BRAF

Outcomes of enfortumab vedotin and pembrolizumab for patients previously treated with immune checkpoint inhibitors in the UNITE study. (ASCO-GU 2025) - "Of 43 pts, 4 received ICI in the peri-operative setting (3 nivolumab, 1 pembrolizumab) and 39 in the metastatic setting (19 pembrolizumab, 8 avelumab maintenance, 6 nivolumab, 2 pembrolizumab maintenance and 1 each of atezolizumab, ipilimumab/nivolumab, durvalumab/tremelimumab, nivolumab/NKTR214). Pts treated with EVP after prior ICI experienced high ORR and disease control rate. Results from this multi-site retrospective study are hypothesis-generating and require prospective validation in larger cohorts. *Continuous."

Checkpoint inhibition • Clinical • Genito-urinary Cancer • Oncology • Urothelial Cancer • PD-1 • PD-L1

Clinical and Translational Results from PORTER, a Multi-cohort Phase 1 Platform Trial of Combination Immunotherapy in Metastatic Castration-Resistant Prostate Cancer. (PubMed, Clin Cancer Res) - P1 | "Cohort B, which combined radiation therapy with CDX-301, poly-ICLC, and nivolumab, demonstrated encouraging clinical activity. Pre-existing rather than treatment-induced immune activation was associated with clinical benefit across cohorts, highlighting the importance of baseline immune fitness."

Journal • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • TNFA

Clinical and Translational Results from PORTER, a Multi-cohort Phase 1 Platform Trial of Combination Immunotherapy in Metastatic Castration-Resistant Prostate Cancer (Clin Cancer Res) - P1 | N=43 | PORTER (NCT03835533) | "43 patients enrolled (N = 14, 15, 14 in Cohorts A, B, C). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 10 (71%), 2 (13%), and 2 (14%) patients, respectively, with one Grade 5 TRAE in Cohort A. Composite response rates were 7% (1/14), 33% (5/15), and 7% (1/14). Across cohorts, 6-month disease control was associated with pre-existing memory/regulatory T cells, TNFα, and other inflammatory pathways....Cohort B, which combined radiation therapy with CDX-301, poly-ICLC, and nivolumab, demonstrated encouraging clinical activity."

P1 data • Castration-Resistant Prostate Cancer

Comparison on the effectiveness of multiple single and double immunotherapy treatments on advanced angiosarcoma patients: Meta analysis & systematic review (ESMO-IO 2024) - "Studies were extracted and evaluated based on inclusion (Accessible full text, Randomized Controlled Trial, Clinical Trials, and last 5 years) and exclusion criterias (non-english text, animal studies, case report, systematic reviews, and meta analysis) The quality of included studies were further assessed using Newcastle-Ottawa Scale (NOS).Results Seven studies consisting of RCTs and clinical trials were included, screening a total of 195 patients. Among the seven studies, bempegaldesleukin + nivolumab yields 0.60 (95% Cl; 0.08-4.40; P < 0.00001), epacadostat + pembrolizumab yields 0.03 (95% Cl; 0.00-0.29; P < 0.00001), ipilimumab + nivolumab yields 0.33 (95% Cl; 0.07-1.49; P < 0.00001), pembrolizumab alone yields 3.33 (95% Cl; 0.36-30.70; P < 0.00001), and Immune checkpoint inhibitors (ICIs) yields 0.13 (95% Cl; 0.02-0.71; P < 0.00001) Adverse effect wise is 17.00 (95% Cl; 0.74-391.68; P < 0.00001), 0.30 (95% Cl; 0.10-0.92; P < 0.00001), 3.00 (95%..."

Metastases • Retrospective data • Review • Angiosarcoma • Oncology • Sarcoma • Solid Tumor

EXPRESSION OF TRANSPOSABLE ELEMENTS AND IKZF1 PREDICTS IMMUNE INFILTRATES IN SARCOMAS AND CORRELATES WITH OUTCOMES AFTER IMMUNE CHECKPOINT INHIBITION (CTOS 2024) - "Here, we update these findings to include analysis of additional cohorts, sarcoma subtype-specific data, on-treatment biopsies, and additional clinical outcome measures We retrospectively analyzed RNA-seq data from our initial cohort of 67 sarcoma patients representing 12 subtypes who were treated on ICI clinical trials (pembrolizumab plus talimogene laherparepvec, nivolumab plus bempegaldesleukin, and pembrolizumab plus epacadostat) including 46 paired pre- and on-treatment biopsies. We identify tumor-intrinsic features that contribute to tumor immune phenotypes, focusing on expression of epigenetic regulators and TEs, which are normally epigenetically silenced and can stimulate inflammatory signaling. In an initial heterogeneous cohort of sarcoma patients treated with ICI, we found that TE and IKZF1 expression predicted immune infiltrates, correlated with PFS, expression of inflammatory pathways, and increased in tumors which gained immune infiltrates during ICI..."

Biomarker • Checkpoint inhibition • IO biomarker • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • IKZF1 • STING

Bempegaldesleukin plus nivolumab in first-line advanced/metastatic urothelial carcinoma: Results from a phase II single-arm study (PIVOT-10). (PubMed, Urol Oncol) - "BEMPEG plus NIVO did not meet the efficacy threshold for ORR in patients with previously untreated locally advanced or metastatic urothelial carcinoma and low PD-L1 expression."

IO biomarker • Journal • Metastases • P2 data • Oncology • Solid Tumor • Urothelial Cancer • IL2 • PD-L1

Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab. (PubMed, NPJ Precis Oncol) - P3 | "Changes in tumor biomarkers were comparable between arms. These biomarker results help provide a better understanding of the mechanism of action of BEMPEG + NIVO and may help contextualize the clinical observations from PIVOT IO 001."

Biomarker • Journal • Tumor mutational burden • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL2 • TMB

PIVOT IO 001: A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma (clinicaltrials.gov) - P3 | N=783 | Completed | Sponsor: Bristol-Myers Squibb | Trial completion date: Sep 2023 ➔ Mar 2024

Metastases • Trial completion date • Melanoma • Oncology • Solid Tumor

Previously Untreated Advanced Clear Cell RCC: Bempegaldesleukin/Nivolumab vs TKI Therapy (THE ASCO POST) - "As reported in the Journal of Clinical Oncology by Nizar M. Tannir, MD, FACP, and colleagues, the phase III PIVOT-09 trial has shown no objective response or overall survival benefit with bempegaldesleukin plus nivolumab vs tyrosine kinase inhibitor (TKI) treatment with sunitinib or cabozantinib in previously untreated patients with intermediate- or poor-risk advanced clear cell renal cell carcinoma. As stated by the investigators, 'Bempegaldesleukin is a pegylated interleukin (IL)-2 cytokine prodrug engineered to provide controlled and sustained activation of the clinically validated IL-2 pathway, with the goal of preferentially activating and expanding effector CD8+ T cells and natural killer cells over immunosuppressive regulator T cells in the tumor microenvironment.'"

Media quote • P3 data

A Study of NKTR-214 in Combination With Nivolumab in Patients With Metastatic and/or Locally Advanced Sarcoma (clinicaltrials.gov) - P2 | N=88 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Solid Tumor

A Placebo Controlled Trial of Bempegaldesleukin (BEMPEG; NKTR-214) With Standard of Care in Patients With Mild COVID-19 (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Nektar Therapeutics | Phase classification: P1b ➔ P1

Phase classification • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

PIVOT IO 011: A Study to Compare Bempegaldesleukin (BEMPEG: NKTR-214) Combined With Nivolumab and Tyrosine Kinase Inhibitor (TKI) to Nivolumab and TKI Alone in Participants With Previously Untreated Kidney Cancer That is Advanced or Has Spread (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed

Trial completion • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

Selective targeting or reprogramming of intra-tumoral Tregs. (PubMed, Med Oncol) - "Anti-CCR8 and the IL-2Rβγ agonist Bempegaldesleukin selectively target intra-tumoral Treg population, with the former approved to not elicit autoimmunity...Blimp-1 inhibitors and glucocorticoid-induced TNFR-related protein agonists are example approaches that can be used for diverting Treg differentiation into Th1-like CD4+ T cells, thereby powering immunogenicity against cancer. Finally, selective target of intra-tumoral Tregs and their reprogramming into effector T cells is applicable using low-dose chemotherapy, and high-salt and high-tryptophan diet."

Journal • Review • Oncology • Solid Tumor • CCR8 • CD4 • PRDM1 • TRPS1

Nektar Therapeutics Reports Third Quarter 2023 Financial Results (PRNewswire) - "Nektar Therapeutics...today reported financial results for the third quarter ended September 30, 2023...G&A expense was $21.1 million in the third quarter of 2023 as compared to $22.5 million in the third quarter of 2022. For the first nine months of 2023, G&A expense was $60.1 million as compared to $70.4 million in the first nine months of 2022. G&A expense decreased for both the third quarter and first nine months of 2023 due to the wind down of the bempegaldesleukin program....CBMG will add NKTR-255 to its ongoing Phase 1 clinical trial being conducted at Duke Cancer Institute. Enrollment for this trial is ongoing."

Commercial • Enrollment status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

PIVOT IO 001: A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma (clinicaltrials.gov) - P3 | N=783 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed | Trial completion date: Feb 2024 ➔ Sep 2023

Metastases • Trial completion • Trial completion date • Melanoma • Oncology • Solid Tumor • PD-L1