From the Journals

Vaccine regimen boosts immune response in malignant melanoma


 

FROM NATURE CANCER

Combining the recombinant Flt3 ligand CDX-301 with the dendritic cell–targeted vaccine CDX-1401 enhanced vaccine-induced immune responses in patients with high-risk melanoma, according to results from a phase 2 trial.

“[This] study supports the potential of combining [the] CDX-1401 vaccine and CDX-301 with checkpoint inhibitors, which are standard-of-care therapy,” study author Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

The team described their study in Nature Cancer.

The multicenter, open-label, randomized study included 60 patients with resected stage IIb-IV melanoma, all of whom had not received any prior treatment, including radiotherapy, biologics, and chemotherapy.

Patients randomized to the combination arm (cohort 1; n = 30) received the anti–DEC-205-NY-ESO-1 vaccine CDX-1401 and were pretreated with CDX-301, while those in the comparator arm (cohort 2; n = 30) received CDX-1401 alone.

Serial blood samples were collected to evaluate response to the vaccine antigen (NY-ESO-1) before each cycle, as well as 4 weeks and 12 weeks after the last vaccination. The primary endpoint was immune response prior to the third vaccination.

T-cell responses were detected in 76% of patients who received CDX-301 and 33% of patients who did not (P < .0011). In addition, the magnitude of response was significantly higher with the combination than with CDX-1401 alone (mean of 41 and 17 corrected spots per well, respectively; P = .032).

“All 30 (100%) cohort 1 participants had NY-ESO-1–specific T-cell responses for at least one time point, whereas 8 (27%) cohort 2 participants had no responses at any time point,” the researchers wrote.

Responses were maintained up to 12 weeks after the final vaccination, but there was no statistically significant difference between cohorts 1 and 2 at 12 weeks (54% and 38%, respectively; P = .2).

The researchers acknowledged that a key limitation of this trial was that it was not sized to evaluate relapse or overall survival.

“Given that ipilimumab, pembrolizumab, and nivolumab are approved as adjuvant therapy for high-risk stage III melanoma, vaccines incorporating CDX-301 and suitable antigen-containing platforms merit clinical investigation in the adjuvant setting in combination with immune checkpoint blockade,” the authors wrote.

“I am hopeful that highly immunogenic cancer vaccines can be added to currently approved immunotherapies, thus boosting an individual’s anticancer immune response even further,” Dr. Bhardwaj said in an interview.

This study was supported by grant funding from the National Cancer Institute. Some authors reported financial affiliations with Celldex Therapeutics, NanoString Technologies, and Oncovir. Dr. Bhardwaj disclosed relationships with Celldex and Oncovir.

SOURCE: Bhardwaj N et al. Nat Cancer. 2020 Nov 16. doi: 10.1038/s43018-020-00143-y.

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