156TiP - The LUNGVAC-study; A randomized phase II, open-label, multicenter study investigating efficacy and safety of anti-PD-1/PD-L1 treatment +/- UV1 vaccination as first line treatment in patients with inoperable advanced or metastatic non-small cell lung cancer (NSCLC)

Background

Programmed Death Ligand 1 (PD1) inhibitors are indicated as monotherapy in first line in patients with stage IIIB/C and IV NSCLC with PD-L1 expression of 50% or above and no EGFR mutation or ALK translocation. Still, under 50% of these patients respond to Immune Checkpoint Inhibitor (ICI) treatment, and there is a need to increase the fraction of patients benefiting from ICI treatment. UV1 is a therapeutic peptide-based cancer vaccine targeting human telomerase (hTERT). hTERT is essential for tumor growth, expressed at high levels in 85% of human tumors, but only sparsely expressed in normal tissues. UV1 induces the expansion of CD4 T cells that recognize specific sequences in the UV1 peptides, and essentially initiates an anti-tumor immune response. UV1 is combined with ICI based on a presumed synergistic activity between the two modalities, as ICI blocks inhibitory signals for a vaccine-induced T cell expansion and anti-tumor effector activity.

Trial Design

The LUNGVAC-study (NCT05344209) is a randomized phase II, open-label, multicenter study evaluating efficacy and safety of anti-PD-1 treatment with or without UV1 vaccination in treatment-naïve patients with advanced or metastatic NSCLC, with PD-L1 ≥ 50%. At least one measurable lesion according to Recist 1.1, adequate organ function, ECOG performance status 0-2 and no other active cancer are main eligibility criteria. Stratification factors are squamous versus non-squamous, and ECOG 2 versus 0+1. Primary endpoint is progression free survival. To test the PFS null hypothesis with 80% power and a 1-sided alpha level of 0.10, a total of 97 PFS events are required. Based on data published for pembrolizumab monotherapy in KEYNOTE-024, to generate the required 97 PFS events, 138 patients will be randomized 1:1 to PD-1-inhibitor for a maximum of 2 years, with or without 8 injections with UV1 vaccine during the first 2 months. Inclusion time is estimated to be 18 months and patients will be followed thereafter for a minimum of 18 months. 20 patients are included as of September 2023.

Clinical trial identification

NCT05344209, EudraCT 2021-005729-25.

Legal entity responsible for the study

Drammen Hospital, Vestre Viken Health Trust.

Funding

Ultimovacs.

Disclosure

E.M. Stensland: Financial Interests, Personal, Advisory Board, AdBoard NSCLC, June 21., 2022: Sanofi. O.T. Brustugun: Financial Interests, Institutional, Advisory Board: MSD, Roche, Takeda, AstraZeneca, Novartis, BMS, Janssen; Financial Interests, Institutional, Funding: Amgen, Ultimovacs; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche. All other authors have declared no conflicts of interest.