LBA99 - First survival data from the NIPU trial: A randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second-line treatment in patients with malignant mesothelioma

Background

Immune checkpoint inhibitors have improved survival for patients with malignant pleural mesothelioma (MPM), but prognosis is still poor. The UV1 telomerase peptide vaccine has demonstrated robust immune response induction and promising clinical activity in several malignancies.

Methods

Patients with MPM progressing after first-line platinum-based chemotherapy were randomized 1:1 to ipilimumab and nivolumab alone (Arm B) or in combination with telomerase vaccine UV1 (Arm A). The primary endpoint was progression-free survival (PFS) evaluated by blinded, independent central review (BICR) at the time of 69 events. The study was powered to detect an HR of 0.60 in favour of arm A with a 1-sided alpha of 0.1.

Results

A total of 118 patients were included and randomized, well balanced with respect to age, gender, performance status, histology and PD-L1 status. The primary endpoint was assessed after a median follow-up of 12.5 months (95% CI 9.7-15.6). The HR for patients treated in arm A was 1.01 (80% CI 0.75-1.36, 95% CI 0.64-1.59) with a median PFS of 4.2 months (95% CI 2.9-9.8) in arm A and 4.7 months (95% CI 3.9-7.0) in arm B. Objective response rate was 31% in arm A and 16% in arm B (odds ratio 2.4, 95% CI 1.0-6.3). The investigator determined median PFS was 4.3 months (95% CI 3.0-6.8) in arm A and 2.9 months (95% CI 2.4-5.5) in arm B with a HR= 0.6 (80% CI 0.45-0.81, 95% CI 0.39-0.94). Overall survival after a median follow-up of 17.3 months (95% CI 15.8-22.9) was 15.4 months (95% CI 11.1-22.6) in arm A and 11.1 months (95% CI 8.8-18.1) in arm B, with a HR of 0.73 (80% CI: 0.53-1.0, 95% CI 0.45-1.18). The total number of adverse events and the proportion of patients experiencing a grade ≥3 adverse event was comparable in the two arms.

Conclusions

The primary endpoint in this study was not met. Supportive analyses indicate an increased ORR and clinically meaningful prolonged survival in the intervention arm. The results warrant confirmation in a larger clinical trial.

Clinical trial identification

EudraCT 2019-002721-30; NCT04300244.

Editorial acknowledgement

Legal entity responsible for the study

Oslo University Hospital.

Funding

BMS, Ultimovacs, South-Eastern Norway Regional Health Authority, The Norwegian Cancer Society.

Disclosure

A. Helland: Financial Interests, Institutional, Advisory Board, Advisory boards: Jansen, Takeda, AstraZeneca, AbbVie, Roche, BMS, Pfizer, MSD, Bayer, Lilly,; Financial Interests, Institutional, Invited Speaker, talks at meetings: AstraZeneca, Roche, AbbVie, Pfizer; Financial Interests, Institutional, Coordinating PI, BMS provides drug to patients in an investigator initiated clinical trial: BMS; Financial Interests, Institutional, Coordinating PI, Ultimovacs provides drug and funds for investigator initiated clinical trial: Ultimovacs; Financial Interests, Institutional, Coordinating PI, AstraZeneca provides drug and funds for investigator initiated clinical trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, Roche provides drug and funds for investigator initiated clinical trial: Roche; Financial Interests, Institutional, Coordinating PI, Novartis provides drug and funds for clinical trial: Novartis; Financial Interests, Institutional, Coordinating PI, Eli Lilly provides drug and funds for clinical stduy: Eli Lilly; Financial Interests, Institutional, Coordinating PI, Incyte provides drug and funds for clinical stduy: Incyte; Financial Interests, Institutional, Coordinating PI, Illumina provides assays for patients in a clinical trial: Illumina; Non-Financial Interests, Other, Board member in the patient organisation until 2022. Provides advice and gives talks.: The lung cancer patients organisation. V.D. Haakensen: Other, Personal, Advisory Board, NSCLC: BMS, Novartis, AstraZeneca; Other, Personal, Invited Speaker, NSCLC: BMS, AstraZeneca; Other, Personal, Writing Engagement, NSCLC: Takeda; Other, Personal, Member: Patient organisation Lung Cancer. S.M.H. Thunold: Financial Interests, Personal, Invited Speaker: BMS. A.K. Nowak: Other, Institutional, Research Funding: AstraZeneca; Other, Personal, Invited Speaker: BMS; Other, Personal, Advisory Board: Douglas Pharmaceuticals. O. Grundberg: Other, Personal, Invited Speaker: Roche. S.J. Farooqi: Financial Interests, Personal, Other, Arranged conference: Merck; Financial Interests, Personal, Other, Made a short film about drug compliance: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS; Financial Interests, Personal, Other, Made a short film about targeted treatment: Amgen; Financial Interests, Personal, Other, Made a short film about Mesothelioma: BMS; Financial Interests, Personal, Advisory Board: BMS. M.M. Bjaanaes: Other, Institutional, Invited Speaker: AstraZeneca, Pfizer, BMS. All other authors have declared no conflicts of interest.