avipendekin pegol (NKTR-255) / Nektar Therap - LARVOL DELTA

Combinational Targeted Chimeric Antigen Receptor NK Cell Therapy to Treat Acute Myeloid Leukemia (ASPHO 2025) - "We hypothesize that anti-CD123 chimeric antigen receptor NK (CD123.CAR NK) cells, combined with adjuvant IL15 Trispecific Killer Engager (TriKE) recognizing CD16 on NK cells and CD33 on AML cells (cam161533), or polymer conjugated IL-15 (NKTR-255), will significantly enhance the anti-tumor activities of NK cells... Combinatorial CD123.CAR NK and adjuvant IL-15 based immunomodulation had significant in vitro anti-AML cytotoxicity. We will investigate the anti-AML effect of the combination utilizing human AML xenografts."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology • CD123 • CD33 • CD34 • GZMB • IL15 • IL3RA

Combinational Natural Killer Cell- Based Therapies Treating Rituximab- Resistant Burkitt Lymphoma (ASPHO 2025) - "Obinutuzumab (OB) is a glycoengineered humanized type-II mAb recognizing a unique CD20 epitope with significantly enhanced antibody-dependent cellular cytotoxicity than rituximab. Our results demonstrated the efficacy of combinatorial NK immunotherapy in treating rituximab-resistant BL cells. Our future studies will determine the in vivo efficacy of NK in combination with cam161519 and OB, and CD20.CAR NK in combination with cam161519 or NKTR-255 in resistant BL models."

Burkitt Lymphoma • Hematological Malignancies • Lymphoma • Oncology • IFNG • IL15

A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley) (clinicaltrials.gov) - P2 | N=256 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2025 ➔ Jul 2026 | Trial primary completion date: Jan 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer

Enhanced CAR T–cell Expansion and Durable Complete Responses with NKTR–255 Plus Lisocabtagene Maraleucel in Relapsed/Refractory Large B–cell Lymphoma (ICML 2025) - No abstract available

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Chemokine engineering significantly enhanced migration and tumor infiltration of ex vivo-expanded natural killer cells in osteosarcoma (AACR 2025) - "To evaluate NK cell tumor infiltration, we injected human NK cells with an IL-15 agonist, NKTR-255, and harvested and dissociated tumors 5-7 days after NK injection for flow cytometry analysis...Our in vitro and in vivo data demonstrated that secretion of CXCL9, -10, and -11 from OS significantly enhanced NK migration and NK infiltration into the OS TME. We are actively investigating the in vivo anti-tumor efficacy of expanded NK cells against CXCL9, -10, or -11-secreting disseminated OS tumors."

Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CXCL9 • CXCR3 • IL15 • IL2 • PTPRC

NKTR-255 Plus Anti-CD19 CAR T-Cell Therapy Demonstrates Safety and Preliminary Efficacy in R/R LBCL (OncLive) - P2/3 | N=15 | NCT05664217 | Sponsor: Nektar Therapeutics | "In the intent-to-treat (ITT) population, the 6-month CR rate was 73% among patients who received NKTR-255 at any dose level (n = 11) vs 50% among those who received placebo (n = 4). The 6-month CR rates among efficacy-evaluable patients in the NKTR-255 (n = 10) and placebo (n = 4) arms were 80% and 50%, respectively. Among patients in the ITT population who received NKTR-255 at dose levels of 1.5 mcg/kg (n = 5), 3.0 mcg/kg (n = 3), and alternating 3.0 mcg/kg and 6.0 mcg/kg (n = 3), the 6-month CR rates were 80%, 67%, and 67%, respectively. The 6-month CR rates among efficacy-evaluable patients in these respective populations were 100% (n = 4/4), 67% (n = 2/3), and 67% (n = 2/3), respectively."

P2/3 data • Diffuse Large B Cell Lymphoma • Large B Cell Lymphoma

NKTR-255 vs Placebo Following CD19-directed CAR-T Therapy in Patients With Relapsed/Refractory Large B-cell Lymphoma (clinicaltrials.gov) - P2/3 | N=15 | Terminated | Sponsor: Nektar Therapeutics | N=400 ➔ 15 | Trial completion date: Jan 2029 ➔ Aug 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jan 2027 ➔ May 2024; Sponsor decided to end the study

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

NCI-2022-02316: NKTR-255 in Combination With CAR-T Cell Therapy for the Treatment of Relapsed or Refractory Large B-cell Lymphoma (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • CD19

Combinatorial Immunotherapy of Mcam Targeting Chimeric Antigen Receptor Modified Expanded Natural Killer Cells and IL-15 Agonist Against Neuroblastoma (TCT-ASTCT-CIBMTR 2025) - "Combination with NKTR-255 further enhanced the anti-tumor effects of CAR NK cells (p < 0.001 compared to vehicle control, p < 0.05 compared to CAR NK), and further prolonged animal survival (100% vs 30% survival at day 126 compared to CAR NK, p < 0.05) (Fig 1D, E). Conclusions Our studies demonstrate that ex vivo expanded and modified anti-MCAM CAR NK cells alone and/or in combination with NKTR-255 are promising novel alternative therapeutic approaches to targeting MCAM high malignant NB."

IO biomarker • CNS Tumor • Melanoma • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • IFNG • IL15 • IL2 • MCAM • NKG2D

Targeting Ewing Sarcoma By IL1RAP CAR Modified Ex-Vivo Expanded TGFβ Imprinted NK Cells in Combination with IL-15 Agonist and Anti-GD2 Antibody (TCT-ASTCT-CIBMTR 2025) - "Conclusions Our data demonstrated enhanced anti-tumor efficacy of IL1RAP CAR NK/TGFβi-NK cells alone and combined with NKTR-255 and dinutuximab against ES in vitro and in vivo. These CAR engineered TGFβi NK cells in combination with NK function and persistence enhancing immune modulators constitute potential novel effective immunotherapies for patients with high-risk ES."

Combination therapy • IO biomarker • Preclinical • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • IFNG • IL15 • IL1RAP • TGFB1 • TGFBI

NKTR-255 Vs Placebo to Enhance Complete Responses and Durability Following CD19-Directed CAR-T Therapy in Patients with Relapsed/ Refractory (R/R) Large B-Cell Lymphoma (LBCL) (TCT-ASTCT-CIBMTR 2025) - P1, P2/3 | "15 patients with LBCL were randomized between Mar and Dec 2023. All patients received CD19-CAR-T cell therapy and ≥1 dose of study treatment; 12/15 (80%) received axi-cel and 3/15 (20%) received liso-cel. In total, 11 were randomized to the NKTR-255 (5 at 1.5 µg/kg; 3 at 3 µg/kg; 3 at 3 µg/kg then 6 µg/kg cycle 2+) and 4 were randomized to placebo."

Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD8 • IL15

A Phase 1 Clinical Trial of NKTR-255 With CD19-22 CAR T-Cell Therapy for Refractory B-Cell Acute Lymphoblastic Leukemia (Cancer Network) - P1 | N=56 | NCT03233854 | "Researchers at Stanford University have conducted a phase 1 clinical trial (NCT03233854) evaluating the combination of a bispecific chimeric antigen receptor (CAR) T-cell therapy targeting CD19 and CD22 (CAR19-22) with NKTR-255...The study enrolled 11 patients, 9 of whom received CAR19-22 followed by NKTR-255. The combination therapy was well-tolerated, with no dose-limiting toxicities. Transient fever and myelosuppression were the most common adverse events. Remarkably, 8 of the 9 patients (89%) achieved measurable residual disease-negative remission, with progression-free survival at 12 months reaching 67%, nearly double the rate of historical controls (38%). These results suggest that combining CAR19-22 with NKTR-255 may significantly improve the durability of remission in B-ALL patients."

P1 data • Acute Lymphocytic Leukemia

NKTR-255 Vs Placebo to Enhance Complete Responses and Durability Following CD19-Directed CAR-T Therapy in Patients with Relapsed/ Refractory (R/R) Large B-Cell Lymphoma (LBCL) (ASH 2024) - P1, P2/3 | "Eligible patients with R/R LBCL were treated with one of two FDA-approved CAR-T products (axicabtagene ciloleucel or lisocabtagene maraleucel). Conclusions : Preliminary data from the randomized, double-blind, placebo-controlled study showed NKTR-255 adjuvant to CD19 CAR-T cell therapy in LBCL was well-tolerated, safe and efficacious to enhance the CR rate of CD19 CAR-T cell therapy alone at month 6. Additional confirmatory studies with NKTR-255 as adjuvant treatment to CAR-T therapy and other cellular therapies are warranted."

Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD8 • IL15

Nektar Therapeutics Announces NKTR-255 Following CD19-directed CAR-T Therapy Enhanced Complete Response Rates in Patients with Relapsed or Refractory Large B-cell Lymphoma at the 66th Annual ASH Meeting (PRNewswire) - P2/3 | N=400 | NCT05664217 | Sponsor: Nektar Therapeutics | "In this multicenter, double-blind Phase 2 study, patients were randomized to receive one of three dose regimens of NKTR-255 or placebo intravenously starting 14 days after CAR-T infusion. In the fifteen-person clinical trial, the NKTR-255 combined treatment group demonstrated an improved CRR at six months, achieving 73% compared to 50% for the placebo....Additionally, two patients treated with NKTR-255 converted from stable disease or partial response to complete responses at six months. No conversions from stable disease or partial response to complete response were observed in the placebo arm of the trial....The reported clinical benefit surpasses the published historical benchmark data from multiple pivotal trials and real-world meta-analyses of currently available commercial CD19 CAR-T cell therapies, which demonstrate 6-month complete response rates of 41% to 44%."

P2 data • Diffuse Large B Cell Lymphoma

REStoring lymphoCytes using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE): preplanned interim safety and efficacy analysis (SITC 2024) - P2 | "Methods NKTR-255 (3µg/kg) is given after CRT (day 0), with repeat doses given every 4 weeks concurrently with durvalumab up to 1 year. Ethics Approval All patients are consented to an institutional review board approved clinical trial protocol.Download figure Open in new tab Download powerpoint Abstract 1489 Figure 1 Trial schema. Schema to show eligibility and workflow of the trial"

Clinical • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15

Combinatorial immunotherapy of anti-MCAM CAR-modified expanded natural killer cells and NKTR-255 against neuroblastoma. (PubMed, Mol Ther Oncol) - "NKTR-255, a polymer-conjugated recombinant human interleukin-15 agonist, significantly stimulated NK cell proliferation and expansion and further enhanced the in vitro cytotoxic activity and in vivo anti-tumor efficacy of anti-MCAM-CAR-NK cells against NB. Our preclinical studies demonstrate that ex vivo expanded and modified anti-MCAM-CAR-NK cells alone and/or in combination with NKTR-255 are promising novel alternative therapeutic approaches to targeting MCAMhigh malignant NB."

IO biomarker • Journal • CNS Tumor • Melanoma • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • IL15 • MCAM

Nektar and Collaborators Present Late-breaking Results from Phase 2 Study of NKTR-255 for the Treatment of Radiation Induced Lymphopenia in Locally Advanced Non-Small Cell Lung Cancer Patients at Society for Immunotherapy of Cancer (SITC) Annual Meeting (PRNewswire) - P2 | N=39 | RESCUE (NCT05632809) | "The combination of NKTR-255 and durvalumab post chemoradiation was shown to be safe and tolerable with an AE profile consistent with previously reported clinical trials. Interim pharmacodynamic data demonstrated statistically significant superiority of the eight-week absolute lymphocyte count with NKTR-255 post chemoradiation and in combination with durvalumab versus non-contemporaneous control groups who received either chemoradiation alone or chemoradiation in combination with durvalumab. Additional pharmacodynamic findings following NKTR-255 administration show increased markers of NK cell proliferation and activation."

Late-breaking abstract • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Nektar Therapeutics Reports Third Quarter 2024 Financial Results (PRNewswire) - "Nektar also announced presentations at the following medical meetings:...2024 American Society of Hematology (ASH) Annual Meeting: Abstract...: 'NKTR-255 Vs Placebo to Enhance Complete Responses and Durability Following CD19-Directed CAR-T Therapy in Patients with Relapsed/Refractory (R/R) Large B-cell Lymphoma (LBCL)''....Presentation Time: Saturday, December 7 at 5:30 PM - 7:30 PM."

P2 data • Diffuse Large B Cell Lymphoma

Nektar Announces Publication in Blood of Phase 1 Data for Novel IL-15 Agonist NKTR-255 in Combination with Autologous CD19-22 CAR-T Cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia (PRNewswire) - P1 | N=56 | NCT03233854 | "The data published in Blood showed favorable efficacy with eight out of nine patients (89%) whom successfully received CAR19-22 followed by NKTR-255 achieving measurable residual disease (MRD) negative remission. The study further demonstrated that, at 12 months, relapse-free/progression-free survival for NKTR-255 in combination with the CD19-22 CAR-T cell therapy was double that of historical controls (67% vs 38%)....Data showed NKTR-255 in combination with CD19-22 CAR-T cell therapy resulted in a 67% 12-month relapse-free survival rate in relapsed or refractory B-ALL and investigators observed significant increases in proinflammatory cytokines and chemokines which suggest lymphocyte trafficking to tissues."

P1 data • B Acute Lymphoblastic Leukemia

Circumventing resistance within the Ewing sarcoma microenvironment by combinatorial innate immunotherapy. (PubMed, J Immunother Cancer) - "Our preclinical studies demonstrate that immunotherapy via the innate immune system by combining tumor-targeting CAR-NK cells with an IL-15 agonist and a CD47 blockade is a promising novel therapeutic approach to targeting MCAMhigh malignant metastatic ES."

IO biomarker • Journal • Ewing Sarcoma • Melanoma • Oncology • Pediatrics • Sarcoma • Solid Tumor • IFNG • IL15 • MCAM

Nektar Therapeutics Reports Second Quarter 2024 Financial Results (PRNewswire) - P1 | N=56 | NCT03233854 | "In July 2024, our collaborators at Stanford published data from a Phase 1 trial evaluating NKTR-255 in combination with CD19/22 CAR-T cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in Blood, an open-access journal of the American Society of Hematology. These data showed that, at 12 months, remission-free survival for NKTR-255 was double that of historical controls (67% vs 38%). The data also showed that eight out of nine patients (89%) achieved complete remission with or without hematologic recovery, all without detectable measurable residual disease (MRD)."

P1 data • B Acute Lymphoblastic Leukemia

A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley) (clinicaltrials.gov) - P2 | N=256 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer

A Phase 1 Clinical Trial of NKTR-255 with CD19-22 CAR-T Cell Therapy for Refractory B-cell Acute Lymphoblastic Leukemia. (PubMed, Blood) - P1 | "The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood and ten-fold increases in CSF CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible and associated with high rates of durable responses (NCT03233854)."

CAR T-Cell Therapy • Journal • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD22 • CD8 • CXCL10 • CXCL9 • IL15

Study of NKTR 255 in Combination With Cetuximab in Solid Tumors (clinicaltrials.gov) - P1/2 | N=25 | Completed | Sponsor: Nektar Therapeutics | Phase classification: P1b/2 ➔ P1/2

Combination therapy • Monotherapy • Phase classification • Anal Carcinoma • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • CD4 • PD-L1

C-TIL051 in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: AbelZeta, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor