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
Nektar Therapeutics (NKTR) announced positive results from its Phase 2 study of NKTR-255 as an adjuvant treatment following CD19-directed CAR-T therapy in patients with relapsed/refractory Large B-cell Lymphoma. The study showed that 73% of patients in the NKTR-255 treatment group achieved complete response at 6 months compared to 50% in the placebo group.
The multicenter, double-blind trial demonstrated that NKTR-255 enhanced CAR T-cell kinetics with improved CD8+ CAR-T area under the curve being 5.8-fold greater than placebo-controls. Two patients treated with NKTR-255 converted from stable disease or partial response to complete responses at six months, while no conversions were observed in the placebo arm.
The treatment was reported to be safe and well-tolerated, with results surpassing historical benchmark data showing 41% to 44% complete response rates at 6 months.
Nektar Therapeutics (NKTR) ha annunciato risultati positivi dal suo studio di Fase 2 su NKTR-255 come trattamento adiuvante dopo la terapia CAR-T diretta contro CD19 in pazienti con Linfoma a grandi cellule B relapsato/refrattario. Lo studio ha mostrato che il 73% dei pazienti nel gruppo di trattamento NKTR-255 ha ottenuto una risposta completa a 6 mesi, rispetto al 50% nel gruppo placebo.
Il trial multicentrico, in doppio cieco, ha dimostrato che NKTR-255 ha migliorato la cinetica delle cellule CAR T, con un'area sotto la curva CD8+ CAR-T che è risultata essere 5,8 volte maggiore rispetto ai controlli placebo. Due pazienti trattati con NKTR-255 sono passati da malattia stabile o risposta parziale a risposte complete a sei mesi, mentre non sono state osservate conversioni nel braccio placebo.
Il trattamento è stato riportato come sicuro e ben tollerato, con risultati che superano i dati di riferimento storici che mostravano tassi di risposta completa del 41% al 44% a 6 mesi.
Nektar Therapeutics (NKTR) anunció resultados positivos de su estudio de Fase 2 sobre NKTR-255 como tratamiento adyuvante tras la terapia CAR-T dirigida contra CD19 en pacientes con Linfoma de células B grandes en recaída/refractarios. El estudio mostró que el 73% de los pacientes en el grupo de tratamiento con NKTR-255 alcanzaron una respuesta completa a los 6 meses, en comparación con el 50% en el grupo placebo.
El ensayo multicéntrico, doble ciego, demostró que NKTR-255 mejoró la cinética de las células CAR T, con un área bajo la curva CD8+ CAR-T que fue 5.8 veces mayor que los controles placebo. Dos pacientes tratados con NKTR-255 pasaron de enfermedad estable o respuesta parcial a respuestas completas a los seis meses, mientras que no se observaron conversiones en el brazo placebo.
Se informó que el tratamiento era seguro y bien tolerado, con resultados que superan los datos de referencia históricos que mostraban tasas de respuesta completa del 41% al 44% a los 6 meses.
넥타르 테라퓨틱스 (NKTR)는 재발성/불응성 대세포 B 림프종 환자에서 CD19 표적 CAR-T 요법 후 보조 치료제로서 NKTR-255의 2상 연구에서 긍정적인 결과를 발표했습니다. 연구에 따르면 NKTR-255 치료 그룹의 73%의 환자가 6개월 동안 완전 반응을 달성한 반면, 위약 그룹은 50%에 그쳤습니다.
다기관, 이중 맹검 임상시험에서 NKTR-255가 CAR T세포 동역학을 개선했으며, CD8+ CAR-T 곡선 아래 면적이 위약 대조군보다 5.8배 더 높았음을 보여주었습니다. NKTR-255로 치료된 두 명의 환자는 6개월 동안 안정병증 또는 부분 반응에서 완전 반응으로 전환되었으나, 위약 그룹에서는 전환이 관찰되지 않았습니다.
치료는 안전하고 잘 견디는 것으로 보고되었으며, 6개월 뒤 41%에서 44%의 완전 반응률을 보인 역사적 기준 데이터를 초과하는 결과였습니다.
Nektar Therapeutics (NKTR) a annoncé des résultats positifs de son étude de Phase 2 sur NKTR-255 en tant que traitement adjuvant après la thérapie CAR-T dirigée contre CD19 chez les patients atteints de lymphome à grandes cellules B en récidive/réfraction. L'étude a montré que 73% des patients du groupe traité par NKTR-255 ont obtenu une réponse complète à 6 mois, contre 50% dans le groupe placebo.
Le procès multicentrique en double aveugle a démontré que NKTR-255 a amélioré la cinétique des cellules CAR T, avec une aire sous la courbe CD8+ CAR-T qui était 5,8 fois supérieure à celle des contrôles placebo. Deux patients traités avec NKTR-255 sont passés d'une maladie stable ou d'une réponse partielle à des réponses complètes après six mois, tandis qu'aucune conversion n'a été observée dans le bras placebo.
Le traitement a été rapporté comme sûr et bien toléré, les résultats dépassant les données de référence historiques qui montraient des taux de réponse complète de 41% à 44% à 6 mois.
Nektar Therapeutics (NKTR) gab positive Ergebnisse aus seiner Phase-2-Studie zu NKTR-255 als adjuvante Therapie nach der CAR-T-Therapie, die auf CD19 abzielt, bei Patienten mit rezidiviertem/refraktärem großzelligem B-Zell-Lymphom bekannt. Die Studie zeigte, dass 73% der Patienten in der NKTR-255-Behandlungsgruppe nach 6 Monaten eine vollständige Remission erreichten, im Vergleich zu 50% in der Placebogruppe.
Die multizentrische, doppelblinde Studie zeigte, dass NKTR-255 die Kinetik von CAR-T-Zellen verbesserte, wobei die Fläche unter der Kurve von CD8+ CAR-T 5,8-mal größer war als bei Placebo-Kontrollen. Zwei Patienten, die mit NKTR-255 behandelt wurden, wandelten sich von stabiler Krankheit oder partieller Reaktion zu vollständigen Reaktionen nach sechs Monaten, während im Placebo-Arm keine Umwandlungen beobachtet wurden.
Die Behandlung wurde als sicher und gut verträglich berichtet, wobei die Ergebnisse die historischen Benchmark-Daten übertrafen, die eine vollständige Reaktionsrate von 41% bis 44% nach 6 Monaten zeigten.
- 73% complete response rate at 6 months vs 50% for placebo
- 5.8-fold improvement in CD8+ CAR-T cell kinetics compared to placebo
- Two patients converted from partial to complete response with NKTR-255
- Results exceeded historical benchmark data of 41-44% complete response rates
- Small trial size with only fifteen participants
Insights
NKTR-255 enhanced CAR T-cell kinetics with improved CD8+ CAR-T area under the curve (AUC) 0-15 days post-administration being 5.8-fold greater than placebo-controls
NKTR-255 is an investigational polymer-conjugated IL-15 agonist, that activates, proliferates and expands natural killer (NK) and CD8+ T-cells in vivo, as well as promotes the survival and expansion of memory CD8+ T cells intended to increase duration and level of response for CAR-T and cellular therapies.1,2
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
"The majority of patients currently receiving CAR-T therapies fail to achieve durable disease remission," said Sairah Ahmed, M.D., Associate Professor, Director of CAR-T Program at the Department of Lymphoma/Myeloma, Division of Cancer Medicine at University of Texas MD Anderson Cancer Center. "The results of this study demonstrated that NKTR-255 enhanced CAR T-cell counts and increased the number of patients who achieve a CR at 6 months post infusion. This finding is highly significant since, in multiple pivotal trials, patients who achieved complete response at 6 months were highly likely to remain in complete response beyond 2 years translating to improved progression-free survival."
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
"This study is the first randomized trial demonstrating adjuvant treatment with NKTR-255 can enhance the durability of response to standard-of-care commercial CAR T-cell therapy by modifying CAR T-cell kinetics," said Mary Tagliaferri, M.D., Chief Medical Officer of Nektar. "These results contribute to the growing body of evidence demonstrating the broad applicability of NKTR-255 in combination with cellular therapies, and, as new data emerge, we continue to explore the best path forward for this program."
NKTR-255 was safe and well-tolerated in patients with relapsed/refractory LBCL in combination with FDA-approved CD19 CAR T-cell products.
Details of the presentation can be found on Nektar's website at www.nektar.com under Scientific Posters, Presentations and Publications.
Title: 2068 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)
Poster: 2068
Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I
Hematology Disease Topics & Pathways: Research, Clinical trials, Clinical Research
Time & Date: Saturday, December 7, 2024, 5:30 PM-7:30 PM
About NKTR-255
NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body's innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory, which may lead to sustained and durable anti-tumor immune response.
In addition to studies in combination with CAR T cell therapies, NKTR-255 is being studied in a Phase 1 clinical trial sponsored by AbelZeta Pharma, Inc., which is evaluating C-TIL051, a tumor-infiltrating lymphocyte therapy, in anti-PD1 resistant metastatic non-small cell lung cancer (NCT05676749). The JAVELIN Bladder Medley study (NCT05327530), sponsored by Merck KGaA, is also ongoing to evaluate NKTR-255 in combination with avelumab as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma (NCT05327530).
About Nektar Therapeutics
Nektar Therapeutics is a clinical-stage biotechnology company focused on developing treatments that address the underlying immunological dysfunction in autoimmune and chronic inflammatory diseases. Nektar's lead product candidate, rezpegaldesleukin (REZPEG, or NKTR-358), is a novel, first-in-class regulatory T cell stimulator being evaluated in two Phase 2b clinical trials, one in atopic dermatitis and one in alopecia areata. Nektar's pipeline also includes a preclinical bivalent tumor necrosis factor receptor type II (TNFR2) antibody and bispecific programs, NKTR-0165 and NKTR-0166, and a modified hematopoietic colony stimulating factor (CSF) protein, NKTR-422. Nektar, together with various partners, is also evaluating NKTR-255, an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer, in several ongoing clinical trials. Nektar is headquartered in San Francisco,
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements which can be identified by words such as: "will," "expect," "develop," "potential," "advance," "anticipate," "can," and similar references to future periods. Examples of forward-looking statements include, among others, statements regarding the therapeutic potential of, and future development plans for, NKTR-255. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of NKTR-255 are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) NKTR-255 is an investigational agent and continued research and development for this drug candidate is subject to substantial risks, including negative safety and efficacy findings in future clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) NKTR-255 is in clinical development, and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (iv) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, competitive factors, or delay or failure in ultimately obtaining regulatory approval in one or more important markets; (v) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vi) certain other important risks and uncertainties set forth in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 8, 2024. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
For Investors:
Vivian Wu of Nektar Therapeutics
628-895-0661
For Media:
Madelin Hawtin
LifeSci Communications
603-714-2638
mhawtin@lifescicomms.com
- Shah, N., Perales, M. A., Turtle, C. J.,
Cairo , M. S., Cowan, A. J., Saeed, H., … Patel, K. K. (2021). Phase I Study Protocol: NKTR-255 as Monotherapy or Combined with Daratumumab or Rituximab in Hematologic Malignancies. Future Oncology, 17(27), 3549–3560. https://doi.org/10.2217/fon-2021-0576 - Miyazaki T, Maiti M, Hennessy M, et al. NKTR-255, a novel polymer-conjugated rhIL-15 with potent antitumor efficacy. Journal for ImmunoTherapy of Cancer 2021;9:e002024. doi:10.1136/jitc-2020-002024
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