Novel Peptide Based Vaccine Demonstrates Safe in Advanced NSCLC

A universal cancer peptide-based vaccine (UCPVax) was highly immunogenic, safe, and demonstrated interesting a 1-year overall survival (OS) rate of 34.1% (95% CI, 23.1-50.4) in heavily pretreated patients with advanced non–small cell lung cancer (NSCLC).¹

UCPVax is a therapeutic vaccine made up of 2 highly selected helper peptides which induce a CD4+ T helper-1 response directed against telomerase.

Findings from the phase 1b/2a trial (NCT02818426) designed to test the safety, immunogenicity, and efficacy of a UCPVax at a 3-dose schedule in patients with metastatic NSCLC were published in the Journal of Clinical Oncology.

“This study showed that UCPVax was equivalently safe and immunogenic through the three dose levels tested and appeared to improve the 1-year OS and progression-free survival [PFS] rates in patients with refractory advanced NSCLC. Most patients [68%] displaying disease control after vaccination were immune responders. Regardless of the dose level, the median OS was doubled in immune responders compared with nonresponders [11.6 months vs 5.6 months, respectively]. The median OS of all the study population was 9 months, and the 1-year survival rate reached 33.0%,” wrote study authors led by Olivier Adotévi, MD, PhD, PhD, head of research team at Molecular Immunotherapy of Cancer.

The prospective, multicenter, phase 1/2 UCPVax study enrolled patients with advanced NSCLC across 5 centers in France. Eligible patients were aged 18-89 who had not received a prior combination of chemoimmunotherapy, had an ECOG performance status of 0 or 1, had an anticipated life expectancy greater than 3 months, and had adequate organ function.²

Part 1b consisted of the 3 dose-escalation part of the study which was performed to determine the highest dose with acceptable toxicity. Primary analyses were performed on the modified intention-to-treat 1 (mITT1) population which included all patients enrolled in phase 1b who received at least 1 dose of vaccine and in the mITT2 population which consisted of all patients who were enrolled in the study who had immune response status available after receiving 3 first doses of vaccine, in phase 1b and 2a, respectively.

Those enrolled in the trial were assigned to receive 3 vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg), followed by phase 2a de-escalating design.

The primary end point of phase 1b was dose-limiting toxicity defined as the grade 3/4 hematologic and nonhematologic immune-related adverse event (AE) which occurred until day 57, and in phase 2a, the primary end point was an immune response after 3 first doses of vaccine. Secondary end points included OS, PFS, and disease response rate.

A total of 59 patients received UCPVax with 15 treated in phase 1b and 44 in phase 2a. This included 18 patients who received dose level 1, 15 who were given dose level 2, and 11 who received dose level 3. Then, the mITT2 analysis set consisted of 51 patients.

Ninety-four patients had received at least 3 prior lines of systemic therapy and the percentage of patients who received > 3 prior lines was equivalent between the 3 dose levels at around 70.0%. In mITT1, the median age was 65.8 years vs 66.6 in mITT2. A majority of patients in each analysis set were male (9 and 34), a current or former smoker (14 and 49), had an ECOG status of 1 (8 and 33), and had adenocarcinoma (10 and 30). In both analyses, all patients had received chemotherapy and immunotherapy.

Findings in the mITT2 population showed that 62.7% and 29.4% of patients were alive at 6 months and 12 months, respectively. Among these patients, 72% and 87% were immune responders to the vaccine regardless of their dose level. Ten (19%) patients in this analysis experienced early disease progression prior to receiving the sixth vaccination and there was no difference between dose levels. At the long-term follow-up, all patients who achieved 18 months of survival were immune responders. Additionally, the PFS rate and median PFS at 12 months in mITT2 were 11.8% (95% CI, 5.5-24.9) and 2.2 months (95% CI, 2.0-2.8), respectively, with no obvious differences observed in regard to dose levels.¹

The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between 3 dose levels. There were 21 (39%) patients who achieved disease control, including 20 who had stable disease and 1 who achieved complete response. The 1-year OS was 34.1% with the median OS at 9.7 months. There was no significant difference between dose levels.

Further, the 1-year PFS and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders (P = .015) and in nonresponders, the median OS was 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5-10; P = .005), respectively.

Regarding safety, there were no dose-limiting toxicities observed in the 15 patients treated in phase 1b and the maximum tolerated dose was determined to be 1 mg. The most frequent treatment-related AEs were grade 1 or 2 injection site reaction/inductions (58.5%), flu-like syndrome (16.1%), and GI disorders, including nausea, vomiting, and diarrhea (8.5%). Injection site reactions were more frequent in those administered dose levels 2 and 3. There were 2 grade 3 lymphopenia (2.0%) observed in DL2 at 0.5 mg, and 1 patient treated with UCPVax at 0.25 mg had a treatment-related grade 5 AE of cerebral vasculitis lesions.

“In conclusion, UCPVax was safe and immunogenic for each dose level tested and showed promising signs of efficacy in patients with refractory advanced NSCLC. This study supports the dose-escalation schema to determine the MTD and the following de-escalation design for immunogenicity and efficacy assessments on the basis of the mechanism of action of anticancer vaccines,” concluded the study authors.

_REFERENCES:

_{1. Adotévi O, Vernerey D, Jacoulet P, et al. Safety, immunogenicity, and 1-year efficacy of universal cancer peptide-based vaccine in patients with refractory advanced non-small-cell lung cancer: A phase Ib/phase IIa de-Escalation study. Published online Sep 7, 2022. J Clin Oncol. doi:10.1200/JCO.22.00096}

_{2. Universal cancer peptide-based vaccination in metastatic NSCLC (UCPVax). ClinicalTrials.gov. Updated September 26, 2022. Accessed October 6, 2022. https://clinicaltrials.gov/ct2/show/NCT02818426}