Nogapendekin Alfa Inbakicept Plus Checkpoint Inhibition Leads to Immune Restoration in NSCLC

Nogapendekin alfa inbakicept (Anktiva) in combination with immune checkpoint inhibition generated statistically significant immune restoration compared with immune checkpoint inhibition alone in the first-line treatment of patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to data from the phase 3 QUILT-2.023 study (NCT03520686).¹

Findings announced by ImmunityBio—the developer of nogapendekin alfa inbakicept—showed that patients treated with nogapendekin alfa inbakicept in combination with immune checkpoint inhibition experienced a statistically significant and sustained increase in absolute lymphocyte count (ALC) from baseline compared with patients given immune checkpoint inhibition alone (P = .0065). Notably, responders to nogapendekin alfa inbakicept plus immune checkpoint inhibition experienced a median overall survival (OS) of 16.2 months compared with 11.8 months for non-responders to the combination (HR, 0.52; P = .0369).

In an announcement, ImmunityBio also shared that in the single-arm phase 2b QUILT-3.055 trial (NCT03228667), restoration or maintenance of an ALC of at least 1.0 x 10³ cells/µL was reported in 77% of patients with NSCLC treated with nogapendekin alfa inbakicept plus immune checkpoint inhibition in the second line or later. In patients who reached an ALC of at least 1.2 x 10³ cells/µL, the median OS was 21.1 months, which was independent of PD-L1 status and bested the historical OS of approximately 7 to 9 months with standard-of-care (SOC) chemotherapy (HR, 0.33; P = .0009).

Detailed findings from both studies will be published in a peer-review publication and shared in future scientific presentations.

“Today, the default SOC for these patients remains cytotoxic chemotherapy such as docetaxel, which is associated with substantial toxicity and limited survival benefit,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer of ImmunityBio, stated in a news release. “The results from these studies support a potential paradigm shift toward what we define as Immunotherapy 2.0, which is the coordinated activation of the innate immune system through natural killer cells and the adaptive immune system through T cells to restore immune competence and extend survival.”

Although nogapendekin alfa inbakicept is not currently approved by the FDA in any lung cancer indications, the agent received approval from the regulatory agency in April 2024 in combination with BCG for the treatment of adult patients with BCG-unresponsive non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors.²

What were the designs of the QUILT-2.023 and QUILT-3.055 trials?

QUILT-2.023 was an open-label, 4-cohort study that enrolled patients at least 18 years of age with histologically confirmed stage III or IV NSCLC; those with stage III disease could not be candidates for surgical resection or chemoradiation.³ Prior systemic therapy in the advanced or metastatic settings was not permitted, although prior neoadjuvant or adjuvant treatment was allowed if completed at least 6 months prior to the diagnosis of metastatic disease. Other key inclusion criteria comprised an ECOG performance status of 0 or 1 and measurable disease per RECIST 1.1 criteria. Those harboring EGFR, ALK, BRAF, ROS1, or NTRK aberrations were not allowed to enroll.

In the primary cohort, patients were randomly assigned to receive nogapendekin alfa inbakicept plus pembrolizumab (Keytruda) or nivolumab (Opdivo) and ipilimumab (Yervoy); or pembrolizumab alone.^1,3 Key stratification factors included checkpoint inhibitor regimen, ECOG performance status, histology, and PD-L1 tumor proportion score.¹

Progression-free survival per RECIST 1.1 criteria served as the trial’s primary end point. Longitudinal ALC was a key prospective, biological end point.

In the open-label, multi-cohort QUILT-3.055 trial, investigators enrolled patients at least 18 years of age with advanced solid tumors who experienced disease progression after prior immune checkpoint inhibition. The study included patients with second- or later-line NSCLC.

Enrolled patients received nogapendekin alfa inbakicept in combination with the same immune checkpoint inhibitor regimen that previously led to a response or stable disease.

The trial’s primary end point was the relationship between ALC response and OS, with a response defined as achieving or maintaining a mean on-treatment ALC of at least 1000 cells/µL.

Following QUILT-2.023 and QUILT-3.055, the ongoing, confirmatory phase 3 ResQ201A trial (NCT06745908) is evaluating nogapendekin alfa inbakicept plus tislelizumab-jsgr (Tevimbra) and docetaxel vs docetaxel alone in the second-line treatment of patients with NSCLC who acquired resistance to a prior immune checkpoint inhibitor.⁴

References

1. ImmunityBio announces positive results demonstrating Anktiva as a lymphocyte stimulating agent in combination with checkpoint inhibitors in non-small cell lung cancer. News release. ImmunityBio. January 13, 2026. Accessed January 14, 2026. https://immunitybio.com/immunitybio-announces-positive-results-demonstrating-anktiva-as-a-lymphocyte-stimulating-agent-in-combination-with-checkpoint-inhibitors-in-non-small-cell-lung-cancer/
2. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. FDA. April 22, 2024. Accessed January 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer
3. Nogapendekin alfa inbakicept for advanced non-small cell lung cancer. ClinicalTrials.gov. Updated October 16, 2025. Accessed January 14, 2026. https://clinicaltrials.gov/study/NCT03520686
4. ResQ201A: clinical trial of N-803 plus tislelizumab and docetaxel versus docetaxel monotherapy in participants with advanced or metastatic non-small cell lung cancer. ClinicalTrials.gov. Updated October 21, 2025. Accessed January 14, 2026. https://www.clinicaltrials.gov/study/NCT06745908