Nogapendekin Alfa Regimens Boost Immune Restoration in NSCLC Trials

Combining nogapendekin alfa inbakicept-pmln (Anktiva) with immune checkpoint inhibitors demonstrated significant immune restoration and a correlation between lymphocyte recovery and prolonged survival among patients with non–small cell lung cancer (NSCLC) across the phase 3 QUILT-2.023 trial (NCT03520686) and the phase 2b QUILT-3.055 trial (NCT03520686), according to a press release from the developer, ImmunityBio.¹

Compared with checkpoint inhibitors alone, nogapendekin alfa plus checkpoint inhibitors showed a statistically significant and sustained improvement in absolute lymphocyte counts (ALC) from baseline among patients with first-line NSCLC in the QUILT-2.023 trial, demonstrating the novel agent’s lymphocyte-stimulating utility (P = .0065). Among those with second- or later-line NSCLC in the QUILT-3.055, combining nogapendekin alfa with immune checkpoint inhibitors restored or maintained an ALC of at least 1.0 x 10³ cells/µL in 77% of patients.

Patients who achieved a response to nogapendekin alfa-based therapy experienced a median overall survival (OS) of 16.2 months compared with 11.8 months among those without a response (HR, 0.52; P = .0369). Additionally, those with an ALC of at least 1.2 x 10³ cells/µL had a median OS of 21.1 months regardless of PD-L1 expression status (HR, 0.33; P = .0009), which surpassed historical values of 7 to 9 months with standard chemotherapy.

According to the press release, investigators are currently assessing nogapendekin alfa plus checkpoint inhibitors vs docetaxel alone among patients with second-line NSCLC as part of the confirmatory phase 3 ResQ201A trial (NCT06745908). Additionally, developers plan to submit detailed findings from the QUILT-2.023 and QUILT-3.055 trials for peer-reviewed publication and scientific presentations in the future.

“Today, the default standard of care for these patients remains cytotoxic chemotherapy such as docetaxel, which is associated with substantial toxicity and limited survival benefit. Large, randomized trials have demonstrated a median [OS] of approximately 9 months with docetaxel,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer at ImmunityBio, stated in the press release.¹ “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.”

QUILT-2.023

In the open-label, multi-cohort, phase 3 QUILT-2.023 trial, patients with stage III or IV squamous or nonsquamous NSCLC were randomly assigned 1:1 to receive checkpoint inhibitors alone or combined with nogapendekin alfa. The trial’s primary end points included progression-free survival (PFS) per RECIST v1.1 criteria and changes in ALC.² Secondary end points included OS, overall response rate (ORR), duration of response (DOR), disease control rate (DCR), and quality of life (QOL).

Patients 18 years and older with histologically confirmed stage III or IV NSCLC, no prior systemic chemotherapy for advanced or metastatic disease, an ECOG performance status of 0 or 1, and measurable tumor lesions per RECIST v1.1 guidelines were eligible for enrollment on the trial. Other eligibility criteria included having a willingness to provide blood samples prior to beginning study therapy and a tumor biopsy specimen 9 weeks after initiating treatment for exploratory analyses.

QUILT-3.055

In the open-label, multi-cohort, phase 2b QUILT-3.055 trial, patients with advanced solid tumors and disease progression following prior checkpoint inhibitor therapy were assigned to continue the same checkpoint inhibitor they had previously received plus subcutaneous nogapendekin alfa as part of each 6-week cycle. The trial had a heavily pretreated population of patients, including those with NSCLC receiving second- or later-line therapy.

The trial’s primary end points were ORR and prolongation of OS based on ALC response.³ Secondary end points included disease-specific survival, PFS, time to response, DOR, DCR, and QOL.

Patients 18 years and older with pathologically confirmed stage IV NSCLC and receipt of exactly 1 anti–PD-(L)1 therapy for advanced disease were eligible for enrollment on the trial. Other eligibility criteria included having an ECOG performance status of 0 to 2 and measurable lesions per RECIST v1.1 guidelines.

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, Inc. January 13, 2026. Accessed January 13, 2026. https://tinyurl.com/eauukmpx
2. Nogapendekin alfa inbakicept for advanced non-small cell lung cancer. ClinicalTrials.gov. Updated October 16, 2025. Accessed January 13, 2026. https://tinyurl.com/45e2jtc6
3. QUILT-3.055: a study of combination immunotherapies in patients who have previously received treatment with immune checkpoint inhibitors. ClinicalTrials.gov. Updated October 17, 2025. Accessed January 13, 2026. https://tinyurl.com/mvyvramt