ASCO-SITC 2019—NKTR-262 + bempegaldesleukin does well in solid-tumor REVEAL


  • Univadis
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Takeaway

  • Doublet therapy with NKTR-262 and bempegaldesleukin (NKTR-214) showed preliminary activity and was associated with local and systemic immunologic effects in patients with locally advanced/metastatic solid tumors.

Why this matters

  • There is a need for effective immunotherapy options for refractory tumors.
  • NKTR-262 is a toll-like receptor (TLR) 7/8 agonist; bempegaldesleukin is a CD122-preferential interleukin-2 (IL-2) pathway agonist.

Study design

  • Interim data from first 4 dose-escalation cohorts in phase 1b/2 REVEAL trial.
    • Phase 1b:
      • 3+3 dose-escalation.
      • Patients relapsed/refractory to >1 checkpoint inhibitor received escalating doses of intratumoral NKTR-262, followed by doublet therapy with intratumoral NKTR-262 plus fixed dose (0.006 mg/kg) intravenous bempegaldesleukin every 3 weeks.
      • Objectives:
        • Evaluate safety, efficacy, correlative biomarkers.
        • Determine recommended phase 2 dose.
    • Phase 2 expansion to test NKTR-262+bempegaldesleukin+nivolumab in earlier lines of therapy, relapsed/refractory setting.
  • Funding: Nektar Therapeutics.

Key results

  • 13 patients received >1 cycle NKTR-262+bempegaldesleukin as of 1/23/2019.
  • Mostly mild, transient systemic toxicity; 1 patient experienced grade 3 rash.
  • Gene expression analysis of tumor biopsies indicated that NKTR-262 promotes local activation of innate immune system, while similar analysis in EXCEL trial indicated that bempegaldesleukin promotes activation of adaptive immune system.
    • Suggests nonoverlapping and synergistic effect, providing abscopal response and systemic tumor immunity.
  • 2/5 melanoma patients, both immune checkpoint inhibitor-refractory, have ongoing partial response.

Limitations

  • Dose escalation ongoing.
  • Data on melanoma patients promising, but preliminary.

Expert comment

  • “The confirmed responses in 2 of 5 melanoma patients are encouraging, but I want to caution, 2 of 5 does not necessarily mean 40 of 100. I think we need more mature data to see how it pans out, but it definitely provides proof of concept. In a patient population that is very difficult to treat, this early result is definitely giving us confidence to pursue this therapy further,” said Shailender Bhatia, MD, Associate Professor, Medical Oncology Division, University of Washington School of Medicine, who was not involved in the trial.

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