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
Nektar Therapeutics and MD Anderson Cancer Center presented late-breaking Phase 2 study results of NKTR-255 for treating radiation-induced lymphopenia in locally advanced non-small cell lung cancer patients. The study showed that NKTR-255, administered after chemoradiation and combined with durvalumab, achieved statistically significant lymphocyte recovery compared to historical controls at week 8. The novel polymer-conjugated IL-15 agonist demonstrated increased NK cell proliferation and activation markers. The RESCUE trial's interim analysis suggests NKTR-255 effectively reversed radiation-induced lymphopenia in patients receiving durvalumab consolidation therapy. The treatment combination proved safe and tolerable, with adverse effects consistent with previous clinical trials.
Nektar Therapeutics e il MD Anderson Cancer Center hanno presentato i risultati dello studio di fase 2 in fase di divulgazione tardiva di NKTR-255 per il trattamento della linfopenia indotta da radiazioni in pazienti con carcinoma polmonare non a piccole cellule localmente avanzato. Lo studio ha dimostrato che NKTR-255, somministrato dopo la chemioradioterapia e combinato con durvalumab, ha raggiunto un recupero linfocitario statisticamente significativo rispetto ai controlli storici alla settimana 8. L'agonista novel a base di polimeri coniugati all'IL-15 ha mostrato un aumento della proliferazione delle cellule NK e dei marcatori di attivazione. L'analisi intermedia dello studio RESCUE suggerisce che NKTR-255 ha efficacemente invertito la linfopenia indotta da radiazioni in pazienti in terapia di consolidamento con durvalumab. La combinazione di trattamenti si è rivelata sicura e tollerabile, con effetti avversi coerenti con studi clinici precedenti.
Nektar Therapeutics y el Centro Oncológico MD Anderson presentaron resultados de estudio de fase 2 de última hora sobre NKTR-255 para tratar la linfopenia inducida por radiación en pacientes con cáncer de pulmón no microcítico localmente avanzado. El estudio mostró que NKTR-255, administrado después de la quimiorradioterapia y combinado con durvalumab, logró una recuperación linfocitaria estadísticamente significativa en comparación con controles históricos a la semana 8. El novedoso agonista de IL-15 conjugado a polímeros demostró un aumento en la proliferación de células NK y en marcadores de activación. El análisis intermedio del ensayo RESCUE sugiere que NKTR-255 invirtió efectivamente la linfopenia inducida por radiación en pacientes que recibieron terapia de consolidación con durvalumab. La combinación de tratamientos resultó segura y tolerable, con efectos adversos consistentes con ensayos clínicos anteriores.
넥타 테라퓨틱스와 MD 앤더슨 암 센터는 국소 진행성 비소세포 폐암 환자의 방사선 유도 림프구 감소증 치료를 위한 NKTR-255에 대한 마지막 순간의 2상 연구 결과를 발표했습니다. 이 연구는 화학 방사선 치료 후에 투여되고 두발루맙과 병용된 NKTR-255가 8주 차에 역사적 대조군에 비해 통계적으로 유의미한 림프구 회복을 달성했음을 보여주었습니다. 새로운 폴리머 결합 IL-15 작용제는 NK 세포의 증식과 활성화 마커의 증가를 나타냈습니다. RESCUE 시험의 중간 분석은 NKTR-255가 두발루맙 유지 요법을 받는 환자에서 방사선 유도 림프구 감소증을 효과적으로 회복시켰음을 시사합니다. 치료 조합은 안전하고 내약성이 있으며, 부작용은 이전의 임상 시험과 일치했습니다.
Nektar Therapeutics et le MD Anderson Cancer Center ont présenté les résultats d'une étude de phase 2 à nouvelles tardives sur NKTR-255 pour traiter la lymphopénie induite par radiothérapie chez des patients atteints de cancer du poumon non à petites cellules localement avancé. L'étude a montré que NKTR-255, administré après chimiothérapie et en combinaison avec durvalumab, a atteint une récupération des lymphocytes statistiquement significative par rapport aux témoins historiques à la semaine 8. Cet agoniste IL-15 conugué à polymères a démontré une augmentation de la prolifération des cellules NK et des marqueurs d'activation. L'analyse intermédiaire de l'essai RESCUE suggère que NKTR-255 a efficacement inversé la lymphopénie induite par radiothérapie chez les patients recevant une thérapie de consolidation avec durvalumab. La combinaison de traitements s'est révélée sûre et tolérable, avec des effets indésirables cohérents avec des essais cliniques précédents.
Nektar Therapeutics und das MD Anderson Cancer Center haben die Ergebnisse einer späten Phase-2-Studie zu NKTR-255 zur Behandlung der durch Strahlung induzierten Lymphopenie bei lokal fortgeschrittenen nicht-kleinzelligen Lungenkrebspatienten vorgestellt. Die Studie zeigte, dass NKTR-255, das nach einer Chemoradiation verabreicht und mit Durvalumab kombiniert wurde, eine statistisch signifikante Lymphozyten-Rückgewinnung im Vergleich zu historischen Kontrollen nach 8 Wochen erreichte. Der neuartige polymer-konjugierte IL-15-Agonist zeigte eine erhöhte Proliferation von NK-Zellen und Aktivierungsmarkern. Die Zwischenanalyse der RESCUE-Studie deutet darauf hin, dass NKTR-255 die durch Strahlung induzierte Lymphopenie bei Patienten, die eine Durvalumab-Konsolidierungstherapie erhalten, effektiv umkehrte. Die Kombinationstherapie erwies sich als sicher und verträglich, mit Nebenwirkungen, die mit früheren klinischen Studien übereinstimmten.
- Statistically significant improvement in lymphocyte recovery compared to control groups
- Treatment combination demonstrated safety and tolerability
- Successful interim analysis results showing efficacy in reversing lymphopenia
- None.
Insights
The Phase 2 study results for NKTR-255 demonstrate promising clinical potential in addressing radiation-induced lymphopenia, a significant concern in NSCLC treatment. The statistically significant improvement in absolute lymphocyte count at week 8 compared to historical controls is particularly noteworthy.
Key findings highlight two critical aspects: First, the drug's ability to effectively restore lymphocyte counts when combined with durvalumab post-chemoradiation. Second, the confirmation of NKTR-255's mechanism of action through increased NK cell proliferation and activation markers. The favorable safety profile aligns with previous clinical data.
While these interim results are encouraging, investors should note that this is an ongoing trial with important endpoints like progression-free survival and overall survival data still pending. The potential market impact could be substantial if final results confirm these early findings, as radiation-induced lymphopenia affects survival outcomes across multiple solid tumors.
The clinical significance of these results extends beyond just lymphocyte count recovery. Radiation-induced lymphopenia is a critical barrier to optimal treatment outcomes in NSCLC, directly impacting patient survival. NKTR-255's novel approach as a polymer-conjugated IL-15 agonist represents a potentially important advancement in supportive cancer care.
The combination with durvalumab is strategically important, as it could enhance the efficacy of immunotherapy in the consolidation setting. The dual action of restoring lymphocytes while promoting NK and CD8+ T-cell function could create a more favorable immune environment for cancer treatment.
However, the use of non-contemporaneous control groups warrants careful consideration when interpreting these results. The true clinical benefit will need to be validated through the study's secondary endpoints.
– NKTR-255 administered post completion of concurrent chemoradiation and in combination with durvalumab demonstrated statistically significant lymphocyte recovery compared to historical controls at week 8 –
– Pharmacodynamic data show NKTR-255 increased NK cell proliferation and markers of NK cell activation –
NKTR-255 is a novel polymer-conjugated IL-15 agonist, designed to activate, proliferate and expand natural killer (NK) and CD8+ T-cells, as well as to promote the survival and expansion of memory CD8+ T cells. NKTR-255 is currently being evaluated in combination with cellular therapies and immune checkpoint inhibitors. Previous pre-clinical and clinical studies have shown that NKTR-255 can proliferate a range of immune cells and augment lymphocyte trafficking.1,2,3
The results from the preplanned interim analysis from the REStoring lymphoCytes Using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE) trial suggest that NKTR-255 effectively reversed radiation induced lymphopenia in patients with locally advanced NSCLC receiving consolidation therapy with durvalumab. Interim pharmacodynamic data demonstrated statistically significant superiority of the eight-week absolute lymphocyte count (ALC) 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.
"Radiation induced lymphopenia is common after chemoradiation therapy and is associated with worse overall survival in multiple solid tumors including lung cancer." said Steven H. Lin, MD, PhD, Professor of Radiation Oncology at MD Anderson. "These interim results showing that NKTR-255 can rapidly restore absolute lymphocyte counts post chemoradiation suggest that NKTR-255 has the potential to confer prognostic benefits and enhanced survival in patients with locally advanced NSCLC."
"These results, combined with the body of evidence previously reported with NKTR-255 in combination with cell therapy, highlight NKTR-255's potential to enhance clinical benefit in both hematologic malignancies and solid tumors" said Mary Tagliaferri, MD, Senior Vice President and Chief Medical Officer at Nektar.
The Phase 2 single-arm study conducted by MD Anderson is evaluating NKTR-255 (3µg/kg IV) following concurrent chemoradiation and in combination with consolidation therapy with durvalumab. NKTR-255 3µg/kg is administered intravenously every 4 weeks in combination with durvalumab (1500mg IV) for up to 1 year (NCT05632809). The primary objectives of the study are safety and ALC normalization at Week 8 after initiation of NKTR-255 and durvalumab post chemoradiation. Secondary endpoints include progression-free survival and overall survival. The trial is currently ongoing at MD Anderson.
Key details and takeaways from the presentation are as follows:
Late-breaking Abstract (LBA) 1489: " REStoring lymphoCytes Using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE): Preplanned Interim Safety and Efficacy Analysis", Lin, S., et al.
- 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.
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 to improve the 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 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. Our pipeline also includes a preclinical candidate NKTR-0165, which is a bivalent tumor necrosis factor receptor type II agonist antibody. 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, California. For further information, visit www.nektar.com and follow us on LinkedIn.
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," "continue," 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 challenges caused by 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 August 9, 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.
Contact:
For Investors:
Vivian Wu of Nektar Therapeutics
628-895-0661
For Media:
Madelin Hawtin
LifeSci Communications
603-714-2638
mhawtin@lifescicomms.com
- NKTR-255, a novel polymer-conjugated rhIL-15 with potent antitumor efficacyJ Immunother Cancer . 2021 May;9(5):e002024.
- A novel polymer-conjugated human IL-15 improves efficacy of CD19-targeted CAR T-cell immunotherapy Hirayama A, et al. Blood Advances 2022.
- A phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia Srinagesh, Blood (2024). 144 (16): 1689–1698.
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FAQ
What were the key results of NKTR-255's Phase 2 study in lung cancer patients?
How is NKTR-255 administered in the Phase 2 RESCUE trial?
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