ANKTIVA® (nogapendekin alfa inbakicept-pmln) demonstrated paradigm-changing efficacy in reversing therapy-induced lymphopenia in checkpoint inhibitor-resistant NSCLC patients, with 80% achieving therapeutic lymphocyte counts and median overall survival extending to 21.1 months in optimal responders. These Phase 2 QUILT-3.055 results support the ongoing Phase 3 ResQ201A trial and establish lymphopenia reversal as an actionable biomarker for improving cancer outcomes.
Study Design & Population
- Study Type: Phase 2 QUILT-3.055 study (NCT03228667)
- Population: 86 patients with advanced NSCLC resistant to checkpoint inhibitor immunotherapy
- Treatment Lines: 51% second-line, 49% third-line-plus patients
- Design: Patients continued their failing checkpoint inhibitor plus ANKTIVA to test lymphopenia reversal hypothesis
- Primary Endpoint: Change in absolute lymphocyte count (ALC) and relationship to median overall survival
Key Findings
- Overall Survival: Median OS of 14.3 months (95% CI 11.7-17.4) for entire study population, with 23 of 86 patients alive at data cutoff
- Lymphopenia Reversal: 80% (69/86) of patients achieved ALC >1,200 cells/µL with median OS of 15.8 months vs 11.5 months in non-responders (p=0.0057)
- Optimal Responders: Patients maintaining ALC ≥1,500 cells/µL achieved 21.1 months median OS (95% CI 13.9-42.1) with some patients alive >4 years
- Lymphopenia Recovery: 60% (25/42) of lymphopenic patients reversed their condition during treatment
- Historical Comparison: Results contrast sharply with 7-9 months survival typically seen with docetaxel in this population
Clinical Implications
- Actionable Biomarker: ALC levels represent the first accessible biomarker for identifying and treating therapy-induced lymphopenia in cancer patients
- Treatment Paradigm: Establishes chemotherapy-free approach by activating natural killer cells and T cells rather than depleting immune system
- Clinical Availability: ANKTIVA already FDA-approved for BCG-unresponsive bladder cancer, providing established safety profile
- Future Applications: May apply across tumor types since lymphopenia affects survival in multiple cancers independent of anatomical location
Development Status & Next Steps
- Phase 3 Trial: Randomized ResQ201A trial (NCT06745908) currently enrolling, comparing ANKTIVA + tislelizumab vs docetaxel alone
- Patient Enrollment: Available through CSSIFM.org for eligible second-line NSCLC patients
- Regulatory Path: Building on existing FDA approval for bladder cancer indication
- Platform Potential: Foundation for BioShield™ platform addressing immune depletion across cancer types
Limitations
- Single-Arm Design: Phase 2 study lacks randomized control arm for definitive efficacy comparison
- Biomarker Validation: ALC threshold optimization and patient selection criteria require Phase 3 validation
- Combination Context: Results obtained with continued checkpoint inhibitor may not translate to ANKTIVA monotherapy
