Immunotherapy Vaccine Prolongs Survival in HLA-A2-Positive Advanced NSCLC

Benjamin Besse, MD, PhD

The immunotherapeutic vaccine OSE-2101 (Tedopi) improved survival by antigen-specific cytotoxic T lymphocytes (CTL) responses in patients with HLA-A2 positive advanced non—small cell lung cancer (NSCLC), according to results from a phase II study presented in a poster at the 34th Society for Immunotherapy of Cancer (SITC) Annual Meeting.

The study enrolled 66 patients with previously treated HLA-A2 positive advanced NSCLC, and of those patients, 33 were evaluated for epitope-specific cytotoxic response and helper T-lymphocyteresponses using an interferon-gamma enzyme-linked immunosorbent assay.

More than 90% of the patients had at least 1 CTL response to 1 vaccine epitope. High responses were observed with 8 epitopes (55% to 91%), but HER2 wildtype and 1 p53 analog had lower responses of 36% and 9%, respectively. Of the 33 patients who were evaluated for 6 epitopes, 3 responses were statistically significant. Notably, patients with CTL response to 3-6 epitopes (n= 23) demonstrated a median overall survival (OS) of 38 months compared to 15 months observed in the 10 patients with CTL response to 0-2 epitopes. Additionally, CTL response to HER2 analog, MAGE3, PADRE and 1 p53 analog were predictive of OS.

Patients received the 1 mL of OSE-2102 via subcutaneous injectionevery 3 weeksfor 6 cycles followed by every 8 weeks for the remainder of the year and every 12 weeks up to the second year. At baseline, leukapheresis for immunogenicity assays were performed during weeks 9, 18, and 30. OS analysis to predict response were performed using Cox regression.

OSE-2102 is now being studied in the phase III ATALANTE trial, in which the vaccine is being compared with the standard of care in HLA-A2-positive advanced NSCLC.

In an interview withTargeted Oncology, Benjamin Besse, MD, PhD, head of Cancer Medicine at the Institut Gustave Roussy Cancer Center,discussedthe research around the Tedopi vaccine and how it addresses an unmet medical need for the treatment of patients with NSCLC who have failed immune checkpoint inhibitors. He also explained the use of genomic testing to aid the treatment of NSCLC.

TARGETED ONCOLOGY: What aretheoptions for patients with NSCLC who fail immune checkpoint inhibitors?

Besse: The standard of care for stageIVNSCLC depends, first of all, on the molecular profile. When you find a driver, you have to use a tyrosine kinase inhibitor, butfor the patients without drivers in their tumors, you have to select either a chemotherapy plus an immunotherapy or immunotherapy alone. Most patients will receive chemotherapy plus immunotherapy. In the case of failure, there are not many options in the second-line setting. Docetaxel is the classic chemotherapy that you can give in this situation, but we need new options.

TARGETED ONCOLOGY: Can you provide background on the Tedopi vaccine?

Besse: Tedopi is a neoepitope-based vaccine. The goal is to reactivate the T-cell reaction against the epitopes. Therapy is quiteuniquebecause it targeted 9 epitopes from 5 antigens plus an additional epitope. It's given subcutaneously to the subpopulation of patients that are HLA-A2 positive.

TARGETED ONCOLOGY: What was the rationale for the phase III ATALANTE-1 trial of Tedopi versus standard of care in HLA-A2 positive advanced NSCLC?

Besse: Tedopi was developed in NSCLC because this therapy targets 5 antigens. We know that at least 1 of these antigens is expressed by the lung cancer cells. When therapy is injected into patients, which has been shown in a phase II trial on 33 patients that has been published, more than 90% of the patients developed at least 1 immune response against the vaccine.

In the phase II study, the overall survival of the patients was 29 months, and what is interesting in that there was a plateau that looks exactly like what is observed in the phase III studies that evaluate the immune checkpoint inhibitors. This serves as a strong rationale to move on to a phase III study with this vaccine.

Additionally, at the 2019 SITC Meeting, we presented a poster (P339) which showed that patients who develop at least 2 immune responses against antigens have a survival that will be double compared to the other patients. This represents more than 60% of the patients in the phase II.

TARGETED ONCOLOGY: What are the methods of design?

Besse: The ATLANTE study is a randomized phase III study in patients who failed immunotherapy and chemotherapy. It’s the second- or third-line setting in which patients who are HLA-A2-positive will be randomized between the standard of care of either single-agent docetaxel or pemetrexed if it wasn’t used in the first-line against Tedopi. The vaccine was given subcutaneously for 6 cycles every 3 weeks and then as a maintenance treatment.

TARGETED ONCOLOGY: Can you explain genomic molecular profile assessment in this trial?

Besse: The standard of care for the management of NSCLC today is to test upfront for drivers for which we have targeted therapies available, so it is mostlyEGFRand ALK. Patients withEGFR- andALK-mutant NSCLC were excluded from the study. We know that the vaccine is potent in patients that are HLA-A2 positive. There is a prescreening on blood to select the patients who are HLA-A2-positive, which is roughly 45% of the world population.

TARGETED ONCOLOGY: What does the safety profile of Tedopi look like? 

Besse: Although the safety profile of Tedopi is good, in the phase II trial, 27% of the patients had local site reactions to the injection. It was mostly grade 1. Almost 20% of the patients developed a flu-like reaction, and some patients developed cytokine release syndrome, which is probably a strong marker of the vaccine potency.

Reference:

Besse, B, Roussy G, Felip E, et al. Survival is improved by antigen-specific cytotoxic T lymphocytes (CTL) responses after treatment with the vaccine Tedopi in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients. Presented at: 2019 SITC Annual Meeting; Nov 6-10, 2020. Poster 339.