Phase 3 trial ResQ201A of nogapendekin alfa inbakicept (NAI) plus tislelizumab and docetaxel vs. docetaxel monotherapy for advanced or metastatic NSCLC resistant to ICI therapy.

Abstract

TPS8671 Background: Immune checkpoint inhibitors (ICIs) are approved as monotherapy and in combination with chemotherapy in advanced NSCLC. Most patients experience progression with limited treatment options other than chemotherapy. NAI is a first-in-class IL-15 receptor agonist that induces proliferation and activation of natural killer cells, CD8+ T cells and memory T cells without activating regulatory T cells, enhancing both the innate and adaptive immune system to maximize immunogenic cell death. Phase 2 data demonstrated evidence of NAI prolonging OS when used in combination with an ICI. The rationale for ResQ201A (NCT06745908) is based on the prior QUILT-3.055 study, wherein median OS was prolonged at 14.3 months overall and 21.1 months when ALC≥1.2x10^3 was maintained with NAI as a lymphocyte stimulating agent. Randomized clinical trials have demonstrated that the standard of care docetaxel in the 2L+ NSCLC setting results in a mOS of approximately 9 months. Methods: ResQ201A is a randomized, open-label phase 3 global, registrational intent trial where 462 adult participants will be enrolled 2:1 in the experimental arm, consisting of two 3-week induction cycles of NAI [SC 1.2 mg], tislelizumab [IV 200 mg] and docetaxel [IV 75 mg/m 2 ] followed by maintenance NAI and tislelizumab, or a docetaxel monotherapy control arm [IV 75 mg/m 2 ] until disease progression or unacceptable toxicity. Participants are stratified based on histology, presence of actionable genomic alterations (AGA), and geographical region. Key inclusion criteria are pathologically confirmed stage IV NSCLC with acquired resistance to an ICI (PD after an initial response OR stable disease ≥ 6 mo. duration) to a single line of ICI with or without chemotherapy, ECOG 0 to 2, and measurable tumor lesions per RECIST v1.1. Key exclusion criteria are systemic autoimmune disease, history of organ transplant, and AGA of ALK. The primary endpoint is OS by KM with treatment arm comparison based on the stratified log-rank test and OS hazard ratio summarized based on the stratified Cox proportional hazard model, both stratified by the randomization strata. Secondary efficacy endpoints include iDCR per iRECIST; PFS, ORR and duration of response. Safety is graded using the NCI CTCAE v5.0. Exploratory analyses will be performed to meet objectives. This trial has enrolled and treated participants. Clinical trial information: NCT06745908 .