OSE2101 Cancer Vaccine Yields Favorable OS vs SOC in HLA-A*02+ ICI-Resistant NSCLC

Benjamin Besse, MD, PhD

The cancer vaccine OSE2101 (Tedopi) significantly extended overall survival (OS) vs standard of care (SOC) chemotherapy for patients with HLA-A*02 phenotype non–small cell lung cancer (NSCLC) who had progressed following treatment with an immune checkpoint inhibitor (ICI), representing a novel treatment approach with a favorable toxicity profile, according to Benjamin Besse, MD, PhD.

The novel T-cell epitope-based vaccine was evaluated in the phase 3 ATALANTE-1 (NCT02654587) where patients with secondary resistance to ICIs achieved a median OS of 11.1 months (95% CI, 8.6-13.5) when treated with OSE2101 (n = 80) vs 7.5 months (95% CI, 4.7-10.3) for those given SOC therapy (n = 38; HR, 0.59; 95% CI, 0.38-0.91; P = .017). However, the vaccine only demonstrated a significant OS benefit in this patient population; those with advanced NSCLC who had received at least 1 line of immune checkpoint blockade given OSE2101 (n = 139) experienced a median OS of 8.8 months (95% CI, 7.6-10.8) vs 8.3 months (95% CI, 6.5-9.8) for patients treated with SOC (n = 80; HR, 0.86; 95% CI, 0.62-1.19; P = .36).

“This phase 3 trial that was unfortunately stopped before completion [due to the COVID-19 pandemic], gives a signal of efficacy in a very particular population—patients with advanced or metastatic NSCLC with positive HLA-A*02 status and with secondary resistance to immunotherapy,” Besse explained in an interview with OncLive^®. “In this particular population, we have a signal of efficacy with a decrease [in] the risk of death [by] 41% and an improvement in quality of life, both because there is control of the disease and less adverse effects [AEs]. The signal must be confirmed with a new phase 3 study that is to be run next year in 2024.”

In the interview, Besse, the director of clinical research and a medical oncologist at the Institute Gustave Roussy in Villejuif, France, discussed the results from the ATALANTE-1 trial and detailed the mechanism of action of the OSE2101 vaccine.

OncLive: How is the OSE2101 cancer vaccine designed?

Besse: This vaccine is made with proteins, meaning it's not an mRNA vaccine, it's 'the old way' to build vaccines. One of the unique facts about this vaccine is that it combines 9 epitopes that are optimized to induce an immune response against 5 different proteins that are usually present at the surface of NSCLC cells. The vaccine only works if patients have the immune phenotype HLA-A*02 and this is something very easy to look at—a simple blood test can easily determine if your patient is HLA-A*02 positive or negative. The positive [phenotype] accounts for [approximately] 45% of the population and only patients with HLA-A*02 positive [disease] will be eligible for the vaccine.

How was ATALANTE-1 conducted?

This is a randomized phase 3 trial that compared the vaccine with SOC. Patients enrolled [had] advanced or metastatic NSCLC and received 1 platinum-based chemotherapy and 1 immunotherapy; both drugs could [have] been given sequentially or combined because at the time we enrolled patients, all the countries [participating in the trial] didn’t have access to first line chemo-immunotherapy.

The trial started in 2016 and patients were stratified according to histology, the line of prior immunotherapy [received], and, importantly, the best response to first-line treatment. Patients received OSE2101 subcutaneously every 3 weeks for 6 injections, then every 8 weeks for up to 1 year, and then every 12 weeks.

In the control arm, patients received either docetaxel, and this was the majority of the patients, [or] pemetrexed when it was not received in the first line and if the histology was non squamous NSCLC. Patients were randomly assigned 2:1 to in the vaccine arm or the control arm. The primary end point was OS.

What were some of the key findings from ATALANTE-1?

The study was started in 2016 and was meant to enroll 363 patients. Unfortunately, the COVID-19 pandemic was an issue for the trial because the first vaccines for COVID-19 appeared on the market and it was difficult to run a study with a tumor vaccine when there was a potential confounding factor with the COVID-19 vaccine. So, we ended the study in 2020 with 219 patients enrolled.

We analyzed this population and a post-hoc analysis was done on the patients that had a degree of sensitivity to the immunotherapy they received upfront. Patients with secondary resistance to immunotherapy, this accounts for 118 patients, [comprised] the population of interest in which we have seen a clear signal.

The signal we have seen is in the primary end point the OS; with the vaccine, the median OS was 11.1 months [compared with] 7.5 months with the single immunotherapy. This translated to a hazard ratio of 0.59 and the P value is significant. To give you another view on the efficacy results, at 1 year in the vaccine arm 44.4% of the patients were alive vs 27.5% in the control arm.

Were there any safety concerns that arose with OSE2101 treatment?

With the vaccine, the AEs were less intense. If we look at the grade 3 or higher AEs, there were 3 times more [drug-related] AEs in the control arm vs the vaccine arm where it was only 11.4%.

With the combination of better efficacy in the population with secondary resistance to immunotherapy and less toxicity, [the vaccine] translated to an increased quality of life. For example, the time to degradation of performance status was much longer in the vaccine arm, 9.0 months vs 3.3 months in the chemotherapy arm. I have to highlight that we are dealing with a very frail population with a lot of comorbidities;[approximately] 90% of our patients were smokers.

The toxicity of the vaccine was mild. At the injection sites, patients could feel a bit of pain and some chills and fever right after the injection. Interestingly, cytokine release syndrome was seen in 7.6% of the patients treated with the vaccine and that probably reflects early activation of the immune system.

How do you see cancer vaccines impacting the treatment paradigm of lung cancer and how do findings from ATALANTE-1 support the further development of cancer vaccines?

Regarding the development of vaccines, it’s been decades that we [have seen] these drugs develop in lung cancer. So far, there were no positive results, and we can see 2 main ways to develop vaccines today. First, the personalized vaccine would be a vaccine [developed] usually based on mRNA technology on which you analyze the tumor of the patients—you can isolate a mutation or neoantigens and then design a specific vaccine according to the molecular profile of the disease.

The other strategy is to use shared antigens between all the different subtypes of NSCLC.[This is] the case with the OSE2101 vaccine, which [is composed of] 9 [synthetic peptides from tumor associated] antigens and you inject small fragments of proteins, but it can be also the case with mRNA vaccines.

We have to keep an eye on the vaccine development, either alone or combined with immunotherapy, [and] either in pretreated patients or untreated patients with advanced disease or with earlier stages [of NSCLC].

Reference

Besse B, Felip E, Garcia Campelo R, et al. Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1. Ann Oncol. 2023;34(10):920-933. doi:10.1016/j.annonc.2023.07.006