‘Best expectation’: Vaccine responses may prevent, delay cancer relapse
Click Here to Manage Email Alerts
Key takeaways:
- A personalized vaccine generated immune responses in patients with head and neck squamous cell carcinoma.
- No patients in treatment arm have relapsed yet.
A personalized cancer vaccine produced T-cell responses in certain patients with head and neck squamous cell carcinoma, according to results from a randomized study presented at American Association for Cancer Research Annual Meeting.
None of the patients treated with the novel vaccine, TG4050, have gone into remission, with one currently at 36 months relapse free.
“It’s our best expectation,” Olivier Lantz, MD, PhD, clinical immunologist at Institut Curie, in Paris, told Healio. “And for the moment, although the trial is not mature enough, it’s very promising because we don’t have recurrence in the vaccine group, and we have three in the control group, which means that the vaccine may be efficient not only immunologically, but clinically.”
Background and methodology
The risk for relapse for patients with head and neck squamous cell carcinoma (HNSCC) is high following surgery, but treatment options for relapsed disease have not proven efficacious, according to background information provided by study investigators and AACR.
Researchers hope TG4050 (Transgene, NEC) becomes a therapeutic option.
“We are part of the big trend, which is to use neoantigens,” Lantz said. “If you stimulate the immune system against this neoantigen, they will recognize, specifically, the tumor cells because only the tumor cells have the mutation.”
TG4050 uses a nonpathogenic form of poxvirus that delivers up to 30 patient-specific neoantigens to initiate T-cell responses.
Individuals had to have completely resected stage III or IV, HPV-negative HNSCC and adjuvant chemotherapy to be included in the trial.
The study cohort consisted of 32 patients. Researchers randomly assigned them in a 1:1 ratio into treatment and control arms. Individuals in the control arm received TG4050 upon relapse.
Researchers administered 20 doses of the treatment over more than a year — once a week for the first 6 weeks, then once every 3 weeks after — and evaluated the safety and immunogenicity of the vaccine.
Results and next steps
At a median follow-up of 18.6 months, researchers reported that no patients in the treatment arm experienced disease relapse. The control arm had three patients who relapsed (after 6.2, 8.8 and 18.5 months).
“We were expecting to have some recurrence, and the fact that we don’t see it is very promising,” Lantz told Healio. “But it’s still too early because when you say a median of [18] months of follow-up, that means that many patients have less than 12 months.”
TG4050 produced CD4 or CD8 responses in 16 of 17 vaccinated patients and stimulated or amplified at least one tumor-specific CD8 response in six of the seven patients evaluated; 80% of reactivity following treatment had not been detected at baseline.
Responses started during the induction period and lasted 211 days after the initiation of treatment.
Researchers did not report any grade 3 or grade 4 adverse events.
“The adverse events are just small site injection-related, some inflammation, but that’s expected with this kind of vector,” Lantz said. “The safety profile is very good. Since the payload is very tumor specific, we do not expect to have any side effects and we don’t.”
The vaccine has limitations, including the time it takes to create — around 3 to 4 months, according to Lantz — the labor needed and the cost.
“The company making the vaccines is improving and streamlining the process, so I think hopefully it will decrease the cost,” he added.
Study limitations included the small cohort and short follow-up time.
Researchers hope to add 23 patients to each arm and further examine the durability of responses.
“One question to answer is the choice of the neoantigen,” Lantz said. “You have plenty of mutations in a tumor. It’s always complicated to choose which neoantigen you should put into the vaccine, and we have some artificial intelligence helping, but we need to make progress.”
References:
- AACR. Investigational personalized vaccine provides clinical benefit for some patients with resected head and neck cancers (press release). Available at: https://www.aacr.org/about-the-aacr/newsroom/news-releases/investigational-personalized-vaccine-provides-clinical-benefit-for-some-patients-with-resected-head-and-neck-cancers/. Published April 9, 2024. Accessed April 9, 2024.
- Lalanne A, et al. Abstract LB401. Presented at: American Association for Cancer Research Annual Meeting; April 5-10, 2024; San Diego.
For more information:
Olivier Lantz, MD, PhD, can be reached at olivier.lantz@curie.fr.
Collapse
Lalanne A, et al. Abstract LB401. Presented at: American Association for Cancer Research Annual Meeting; April 5-10, 2024; San Diego.
Click Here to Manage Email Alerts