A New Cancer Vaccine Offers Hope for Advanced Lung Cancer

Efforts to treat cancer with vaccines have a history of approximately 130 years. The first agents used were bacteria (see Coley’s toxins). However, consistent, meaningful and predictable responses to therapeutic cancer vaccines were not achieved until the 2010s. Only a few therapeutic cancer vaccines have received FDA approval, including Lmlygic for melanoma and Provenge for prostate cancer. 

Cancer vaccines tested so far share a common aim: stimulating the immune system against cancer. In this sense, they are a form of immunotherapy. Early human trial results for a newly developed cancer vaccine were published in the leading oncology journal Journal of Clinical Oncology on September 7, 2022.

In a French phase Ib/IIa study reported by Adotevi and colleagues, the therapeutic peptide-based cancer vaccine UCPVax was studied in patients with refractory advanced non-small cell lung cancer . It triggered specific CD4+ T helper-1 responses in many patients, and vaccine responders benefited from treatment.

What Is a Peptide-Based Cancer Vaccine?

A cancer vaccine aims to activate patients’ immune systems, preparing them to recognize, attack and destroy tumor cells. Peptide vaccination approaches use synthetic peptide forms of tumor-specific antigens to design a vaccine. Peptide-based cancer vaccines generally consist of 20-30 amino acids containing specific epitopes from antigens known to be highly immunogenic, to induce the desired immune response. They have advantages over other vaccine types, particularly in safety and ease of production.

Personalized peptide-based cancer vaccines derived from tumor-specific genetic studies are also being investigated.

UCPVax for Lung Cancer

UCPVax is designed to induce an antitumor CD4+ T helper-1 cell response. This new therapeutic cancer vaccine consists of two highly selected helper peptides.  

Study Details

Approximately 60 patients with previously treated advanced non-small cell lung cancer that had become treatment-resistant entered this multicenter study between April 2016 and July 2021.

Treatment consisted of vaccine doses of 0.25 mg, 0.5 mg or 1 mg on days 1, 8, 15, 29, 36 and 43, followed by a booster every 8 weeks for up to 12 months.

A total of 15 patients entered phase Ib, and 51 evaluable patients were treated in phase IIa. Of the 51, 15 received 0.25 mg, 16 received 0.5 mg and 20 received 1 mg. Overall, 95% had previously received three lines of systemic therapy. 

Key Findings

• No dose-limiting adverse events occurred in phase Ib, and the maximum tolerated dose was established as 1 mg.
• In phase IIa, the third and sixth UCPVax doses triggered specific CD4+ T helper-1 responses in 56% of 51 patients and 87.2% of 39 patients, respectively. There was no significant difference among the three dose levels.
• After the third dose, responses occurred in 7 of 15 patients receiving 0.25 mg, 9 of 16 receiving 0.5 mg and 13 of 20 receiving 1 mg. Almost all 18 patients assessed after boosters had a response.
• There was disease control in 21 patients, comprising 20 with stable disease and 1 complete response (39%) .
• Across all 51 patients, 1-year overall survival was 34.1% (95% confidence interval [CI] = 23.1–50.4%), and median overall survival was 9.7 months (95% CI = 6.7–12.6 months), without significant differences among dose levels.
• For immune responders and nonresponders after three doses, 1-year progression-free survival was 17.2% (95% CI = 7.8%-38.3%) and 4.5% (95% CI = 0.7%–30.8%, P = 0.015), respectively. Median overall survival was 11.6 months (95% CI = 9.7–16.7 months) and 5.6 months (95% CI = 2.5–10 months, P  = 0.005). At 1 year, overall survival was 47.5% (95% CI = 32.2%-70.0%) and 18.2% (95% CI = 7.5%-44.1%).

The most common treatment-related adverse events were grade 1 or 2 injection-site reactions (58.5%), flu-like symptoms (16.1%) and gastrointestinal disorders (8.5%). Injection-site reactions were more common at 0.5 mg and 1 mg. One patient receiving 0.25 mg had grade 5 cerebral vasculitis lesions; the event was considered possibly treatment-related and unexpected.

Conclusion

In conclusion, UCPVax was highly immunogenic (immune-stimulating) and safe in this study, providing a better-than-expected 1-year overall survival rate in heavily pretreated advanced non-small cell lung cancer. Based on these favorable results, researchers will initiate a larger phase III study.

Peptide-based vaccines offer advantages over other personalized cellular therapies derived from a person’s tumor, including easier preparation, greater accessibility and affordability. Whether adding these vaccines to other immunotherapies will improve outcomes remains an open question.

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NOTE: Although UCPVax and the Cuban vaccine have similar mechanisms, there are critical differences. The immune response offered by the Cuban vaccine CimaVax acts through antibodies rather than the main immune cells (T cells, NK cells and macrophages), and therefore provides a short-lived, weak immune response. UCPVax acts through CD4+ T cells and may thus provide a stronger and more effective antitumor immune response.