LK101 Plus Tislelizumab Elicits Responses in Advanced NSCLC

The addition of LK101, a personalized neoantigen dendritic cell vaccine, to first-line maintenance with tislelizumab-jsgr (Tevimbra) generated early antitumor activity in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC), according to data from a phase 1b/2a study (NCT05886439) presented at the 2026 ESMO Congress.¹

As of a March 31, 2026, data cutoff, 4 of the 21 patients evaluable for response had a confirmed partial response (PR), for an investigator-assessed objective response rate (ORR) of 19.0% (95% CI, 5.4%-41.9%). The investigator-assessed disease control rate (DCR) was 95.2% (95% CI, 76.2%-99.9%). At a median follow-up of 9.5 months from the start of first-line therapy, the median progression-free survival (PFS) had not been reached.

"These preliminary clinical and immunologic findings support further evaluation of LK101 plus tislelizumab in the first-line maintenance setting. A randomized controlled phase 2 trial is being initiated," Jianchun Duan, MD, PhD, said in the presentation. Duan is a study investigator with the Department of Medical Oncology at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing, China.

What is the mechanism of action of LK101?

LK101 is manufactured individually for each patient: the patient's own dendritic cells are transfected with mRNA that encodes as many as 30 tumor neoantigens unique to that patient. To design the construct, investigators perform whole-exome and RNA sequencing on tumor tissue and a matched normal sample, then identify mutations, perform HLA typing, and predict and rank candidate neoantigens.

In parallel, monocytes enriched from a leukapheresis product are differentiated into mature dendritic cells, which take up the neoantigen mRNA via electroporation and are then formulated, cryopreserved, and given as an intradermal injection. By expanding T cells that recognize these neoantigens, the vaccine is designed to work alongside PD-1 blockade and augment antitumor immunity.

How was the trial designed?

The open-label, single-arm study features a cohort assessing LK101 plus tislelizumab and pemetrexed maintenance. The trial also includes cohorts evaluating LK101 plus pembrolizumab (Keytruda) in NSCLC that progressed on prior anti–PD-1/PD-L1 therapy and LK101 plus durvalumab (Imfinzi) in extensive-stage small cell lung cancer.²

To qualify for prescreening, patients needed to be at least 18 years of age with NSCLC that was locally advanced or metastatic and could not be treated with surgery, radiotherapy, or chemoradiotherapy.¹ Patients also needed a PD-L1 tumor proportion score (TPS) of 1% or higher, no actionable genomic alterations, and an ECOG performance status of 0 or 1.

All patients first received 4 to 6 induction cycles of platinum-doublet chemotherapy with an anti–PD-1 monoclonal antibody. Those whose disease had not progressed then entered main screening, which called for at least 1 lesion measurable by RECIST 1.1 criteria, a successful neoantigen screen, venous access suitable for leukapheresis, and adequate organ function. Planned enrollment was 30 patients.

After a 14-day rest following the last induction dose, patients entered a 4-week study screening window, during which LK101 was manufactured over approximately 2 to 3 weeks.

Maintenance consisted of tislelizumab at 200 mg IV every 3 weeks, plus pemetrexed at 500 mg/m² IV every 3 weeks for those with nonsquamous disease. LK101 was injected intradermally once weekly for 4 priming doses, every 3 weeks for 3 booster doses, and every 6 weeks thereafter as maintenance, for up to 1 year in total. Tislelizumab, with or without pemetrexed, could continue for up to 2 years, and treatment proceeded until disease progression or intolerance.

Safety served as the primary end point. Safety assessments encompassed the incidence of dose-limiting toxicities; the incidence and severity of adverse effects (AEs), serious AEs (SAEs), and immune-related AEs (irAEs); and clinically significant laboratory or other test abnormalities, with monitoring continuing until 90 days after treatment ends.²

Secondary end points in the presentation included PFS, overall survival (OS), ORR, DCR, and immunogenicity.¹

Of 26 patients enrolled by the cutoff, 25 received LK101. The median age of treated patients was 62 years (range, 40-73), 36.0% were 65 years of age or older, and 88.0% were male. Nonsquamous histology was present in 64.0% of patients vs squamous histology in 36.0%.

All but 1 patient had stage IV disease (96.0%); the remaining patient had stage IIIC disease. PD-L1 tumor proportion score was 1% to 49% in 52.0% of patients and 50% or higher in 48.0%.

Lymph nodes (76.0%) and lung (56.0%) were the most frequent metastatic sites; bone, brain, and liver metastases were present in 16.0%, 12.0%, and 4.0% of patients, respectively. The median number of metastatic sites was 2 (range, 1-3). Best response to induction therapy was a PR in 60.0% of patients and stable disease in 40.0%.

What additional efficacy findings were reported?

In the nonsquamous subgroup (n = 15), the ORR was 6.7% (95% CI, 0%-31.9%) and the DCR was 100% (95% CI, 78.2%-100%). In the squamous subgroup (n = 6), the ORR was 50.0% (95% CI, 11.8%-88.2%) and the DCR was 83.3% (95% CI, 35.9%-99.6%).

Measured from the start of first-line therapy, the 9- and 12-month PFS rates were 85.4% and 70.4%, respectively; because these estimates are anchored to first-line initiation, they include time on induction before vaccination. Duration of response, PFS, and OS calculated from the first LK101 dose were not yet mature.

ELISpot responses rose by a median of 30-fold after dosing compared with baseline. After priming, ELISpot reactivity was greater among patients with a PR than among those without one (Wilcoxon P < .01). Lymphocyte analyses after the fourth priming dose also showed increases from baseline in the proportion of effector T cells among CD3-positive T cells (P < .001), CD8-positive T cells among CD3-positive T cells (P < .001), and effector cells among CD8-positive T cells (P = .026).

Because the cohort was small and lacked a randomized control arm, these results cannot isolate the contribution of LK101 beyond the maintenance backbone.

What safety findings were reported?

Among the 25 treated patients, 96.0% experienced treatment-emergent AEs (TEAEs), and 24.0% had grade 3 or higher TEAEs. LK101-related TEAEs occurred in 64.0% of patients and were mostly grade 1 or 2; grade 3 or higher LK101-related TEAEs were reported in 8.0%.

SAEs occurred in 28.0% of patients, including LK101-related SAEs in 12.0%, which consisted of pneumonitis, dry mouth, and peripheral edema. irAEs were reported in 28.0% of patients and were considered related to LK101 in 20.0%. One patient (4.0%) had an infusion reaction.

The most frequent TEAEs of any grade were increased aspartate aminotransferase (n = 7), increased alanine aminotransferase (n = 6), decreased neutrophil count (n = 6), decreased white blood cell count (n = 5), and asthenia (n = 4). Grade 3 or higher decreased neutrophil count occurred in 3 patients.

LK101-related TEAEs prompted LK101 interruption in 32.0% of patients and discontinuation in 4.0%. A single fatal TEAE was deemed unrelated to LK101, and no TEAEs resulted in study withdrawal.

References

1. Wang J, Wang Z, Duan J, et al. Phase 1b/2a study of LK101, a personalized neoantigen DC vaccine, as first-line maintenance therapy in locally advanced/metastatic NSCLC. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract 1950RO.
2. A study of LK101 combined with PD-1 or PD-L1 monoclonal antibody in the treatment of lung cancer to evaluate the safety, tolerability and preliminary efficacy. ClinicalTrials.gov. Accessed October 24, 2026. https://clinicaltrials.gov/study/NCT05886439