ImmunityBio announced breakthrough findings from its Phase 2 QUILT-3.055 study showing that ANKTIVA (nogapendekin alfa inbakicept-pmln) reverses lymphopenia in patients with checkpoint inhibitor-resistant advanced non-small cell lung cancer (NSCLC), resulting in significantly prolonged median overall survival. The results were presented at the IASLC 2025 World Conference on Lung Cancer in Barcelona, Spain.
Clinical Efficacy and Survival Outcomes
The study demonstrated that patients with absolute lymphocyte counts (ALC) greater than 1,500 cells/μL achieved a statistically significant prolonged median overall survival of 21.1 months (95% CI: 13.9, 42.1). This represents a dramatic improvement compared to the historical 7 to 9 months survival with docetaxel in patients with advanced lung cancer, with some patients remaining alive for over 4 years.
Among the 86 study participants with NSCLC, including patients in second line (51%) and third line-plus treatment (49%), the median overall survival was 14.3 months (95% CI 11.7, 17.4), with 23 participants alive at the December 2024 data cutoff.
Lymphocyte Count Recovery and Clinical Impact
The study revealed that 80% of patients (69 of 86) exceeded an ALC of 1,200 cells/μL while receiving ANKTIVA treatment. These patients demonstrated a median overall survival of 15.8 months (95% CI 12.6, 21.9) compared to participants who failed to achieve ALC>1,200 cells/μL, who had a median overall survival of 11.5 months (95% CI 4.2, 13.3); p=0.0057.
Notably, 60% of participants (25/42) treated with ANKTIVA reversed their lymphopenia during at least one on-treatment timepoint. Participants with a baseline ALC≥1,200 cells/μL and a group mean ALC≥1500 cells/μL at each on-treatment time point (N=44) demonstrated the greatest prolonged overall survival of 21.1 months.
Addressing Treatment-Induced Lymphopenia
Severe lymphopenia, defined by an absolute lymphocyte count of less than 1,000 lymphocyte cells/μL, is an adverse treatment effect associated with chemotherapy, radiotherapy, and immunotherapy that significantly lowers overall survival in non-small cell lung cancer and multiple types of cancer. ANKTIVA represents the first FDA-approved lymphocyte-stimulating agent specifically designed to address this condition.
"These results present the clinical evidence that a low lymphocyte count, as measured by ALC levels, is an actionable, accessible biomarker to identify and treat therapy-induced lymphopenia in cancer patients with ANKTIVA and prolong overall survival," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio.
Mechanism of Action and Therapeutic Approach
ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex that stimulates natural killer cells, CD4+ CD8+ T cells and memory T cells - the very cells that are depleted in lymphopenia. The therapy works by activating NK cells and T cells, which are key lymphocytes involved in inducing cancer cell death.
Dr. Soon-Shiong emphasized the paradigm-shifting potential of this approach: "By taking this approach, we hope to herald in the paradigm change of treating the immune system itself and thereby allow the immune system to cure the cancer, regardless of its anatomical location."
Study Design and Methodology
The Phase 2 QUILT-3.055 study (NCT03228667) enrolled participants with advanced NSCLC who had developed resistance to checkpoint inhibitor immunotherapy. Participants continued treatment with the same checkpoint inhibitor on which they had progressed, combined with ANKTIVA, to test the hypothesis that ANKTIVA could improve overall survival by reversing lymphopenia and maintaining median ALC≥1,200 cells/μL.
The primary endpoint was the change in ALC, including absolute cell count and percentage change from baseline, with ANKTIVA plus checkpoint inhibitor during the study and its relationship to median overall survival.
Future Development and Phase 3 Trial
Patients are currently being enrolled in the randomized Phase 3 ResQ201A trial (NCT06745908), which is evaluating ANKTIVA plus tislelizumab, a checkpoint inhibitor, versus docetaxel alone in second-line NSCLC patients who have progressed after all standard therapies, including checkpoint inhibitors.
ANKTIVA is currently approved by the U.S. Food and Drug Administration with Bacillus Calmette-Guérin (BCG) for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ, with or without papillary tumors.
