Why the study?
While immunotherapy has improved outcomes in NSCLC, its efficacy is limited in many patients, warranting exploration of combination strategies such as the telomerase-targeting UV1 vaccine to enhance immune response and overcome checkpoint inhibitor resistance.
Does the addition of UV1 + GM-CSF vaccinations to standard of care PD-1 inhibitors improve progression-free survival in patients with advanced NSCLC?
Does the addition of UV1 + GM-CSF vaccinations to standard of care PD-1 inhibitors improve progression-free survival in patients with advanced NSCLC?
The addition of the UV1 vaccine to standard PD-1 inhibitor therapy was well tolerated but did not significantly improve progression-free survival in patients with advanced NSCLC.
Background: While immunotherapy has improved outcomes in NSCLC, its efficacy is limited in many patients, warranting exploration of combination strategies such as the telomerase-targeting UV1 vaccine to enhance immune response and overcome resistance to checkpoint inhibitors.Methods: This randomized, multicentre, open-label phase II trial evaluated efficacy and safety of standard of care (SoC) PD-1 inhibitor +/-UV1, and enrolled patients with stage IIIB/C or IV NSCLC, ECOG 0-2 and PD-L1 expression 50%, eligible for first-line PD-1 inhibitor monotherapy.Patients were randomized 1:1 to SoC (pembrolizumab or cemiplimab) alone or in combination with eight UV1 + GM-CSF vaccinations s.c.over 13 weeks.Primary endpoint was progression free survival (PFS) stratified by histology and ECOG status; secondary endpoints included overall survival (OS), objective response rate (ORR), time to response (TTR), duration of response (DoR) and safety.Results: Baseline characteristics were comparable across arms (n=15 each; inclusion was stopped early due to slow recruitment): 67% male in both arms, median age 70 vs 74 years, 20 vs 13 % ECOG 2 and 67-73% non-squamous histology.At a median PFS follow-up of 24 months, UV1 + SoC demonstrated no significant benefit over SoC (8 mo vs 7 mo, HR=0.92; 95% CI: 0.42 -2.02).Median OS was not reached in the UV1 + SoC arm and 24 months (95% CI: 0.00 -49.43) in the SoC arm, HR = 0.60 (95% CI: 0.21 -1.66).12-month OS rates were 73.3 % (UV1 + SoC) and 60% (SoC).TTR and ORR were 2 mo and 53.3 % (UV1+SoC) vs 3 mo and 46.7 % (SoC) (HR=0.96,95% CI: 0.35-2,67), and median DoR was 17 mo (UV1+SoC) vs 11 mo (SoC) (HR=0.79;95% CI: 0.25-2.46).AEs occurred in 90% of patients, with grade 3 in 53%; most frequent were rash, lung infection, and liver enzyme elevations.More AEs were reported in the UV1+SoC arm (n=66 vs 47).No grade 3 AEs were deemed related to UV1, including two deaths (stroke, pneumothorax).Conclusions: UV1 in combination with SoC was well tolerated but did not significantly improve PFS or DoR.Although OS was not significantly longer in UV1-treated patients, a numerical OS advantage was seen, warranting further investigation and longer follow-up.
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Saito et al. (2026) studied this question.
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