American Association for Cancer Research Annual Meeting

American Association for Cancer Research Annual Meeting

Perspective from Dmitriy Zamarin, MD, PhD
Source:

Marron TU, et al. Abstract LB048. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

Disclosures: Marron reports advisory or data safety monitoring board roles with AstraZeneca, Atara Biotherapeutics, Boehringer Ingelheim, Celldex Therapeutics, Genentech and Regeneron, and research support from Bristol Myers Squibb, Boehringer Ingelheim and Regeneron. See the abstract for all other researchers’ relevant financial disclosures.
April 13, 2021
3 min read
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Personalized vaccine shows potential benefit across cancer types

Perspective from Dmitriy Zamarin, MD, PhD
Source:

Marron TU, et al. Abstract LB048. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

Disclosures: Marron reports advisory or data safety monitoring board roles with AstraZeneca, Atara Biotherapeutics, Boehringer Ingelheim, Celldex Therapeutics, Genentech and Regeneron, and research support from Bristol Myers Squibb, Boehringer Ingelheim and Regeneron. See the abstract for all other researchers’ relevant financial disclosures.
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A personalized genomic vaccine administered after standard-of-care adjuvant therapy appeared safe and induced immunogenicity among patients with different cancers at high risk for recurrence, according to results of a phase 1 trial.

The findings, presented at the virtual American Association for Cancer Research Annual Meeting, also showed feasibility of developing the neoantigen cancer vaccine, PGV-001, using Mount Sinai’s computational platform, OpenVax.

A personalized genomic vaccine administered after standard-of-care adjuvant therapy appeared safe and induced immunogenicity.
Data were derived from Marron TU, et al. Abstract LB048. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

“This was the first [cancer vaccine] trial that enrolled a heterogeneous mix of tumors, all of which had a very high chance of recurrence,” Thomas Marron, MD, PhD, assistant director of immunotherapy and early-phase trials at Tisch Cancer Institute and assistant professor of medicine, hematology and medical oncology at Icahn School of Medicine at Mount Sinai, told Healio.

Thomas Marron, MD, PhD
Thomas Marron

“[Patients in the cohort] had already recurred and they were having a second or third surgery,” he continued. “Three of the patients had multiple myeloma and were undergoing a stem cell transplant. It was a very high-risk population and a population that can definitely use some help.”

Patients who do not respond to immunotherapy are believed to lack adequate priming of T cells to tumor-specific neoantigens. To address this challenge, Marron and colleagues developed PGV-001 with patient-specific synthetic neoantigen peptides (25 mer).

To create the vaccine, researchers sequenced tumor and germline DNA and tumor RNA of 15 patients who had undergone curative-intent surgery for solid tumors or autologous stem cell transplant for multiple myeloma and had at least a 30% chance of recurrence. The OpenVax pipeline then used that data to identify and prioritize candidate immunogenic neoantigens that could be synthesized and incorporated into the vaccine, using up to 10 neoantigen peptides — which were specific to the patient’s HLA type to help predict the potential for their immune recognition — per patient.

The OpenVax pipeline identified an average of 67.1 neoantigens (range, 8-193) per patient and only failed to identify enough neoantigens to synthesize 10 peptides for two patients, demonstrating feasibility of the approach, according to researchers.

The remaining 13 patients — including 10 with solid tumor diagnoses and three with multiple myeloma — received at least seven doses of vaccine. Eleven of the patients received all 10 planned doses of the vaccine over 6 months. Patients also received the immunostimulant poly-ICLC and a tetanus helper peptide, which helps to further activate the immune response against the vaccine’s neoantigens.

Mean follow-up was 925 days.

After excluding one patient lost to follow-up, median PFS from the time of surgery or HSCT was 618 days.

Four patients remained without evidence of disease — including one patient each with myeloma, lung cancer, breast cancer and urothelial cancer — four patients were receiving subsequent lines of therapy and four patients died, two due to disease recurrence.

Initial analysis of patient samples confirmed immunogenicity, with T-cell responses and intracellular cytokine staining showing induction of interferon-gamma, tumor necrosis factor-alpha and interleukin-2.

“We looked at the blood straight away, not manipulating it at all, after the first six injections and we actually barely could detect any response to the vaccine,” Marron said. “But, 27 weeks later, after all 10 vaccines, we saw this amazing, robust response against the majority of antigens that the first patient received.”

Researchers also conducted immune monitoring by collecting serial blood samples.

“In the first patient, we saw that we successfully induced not only CD4 but CD8 T-cell response against their tumors,” Marron said. “So, basically both sides of the immune system recognized the peptides that we were vaccinating them with, which was obviously the goal.”

The vaccine appeared well-tolerated, with grade 1 injection-site reactions occurring among about one-third of patients.

Marron said he sees potential in future research aimed to optimize creation and use of the personalize vaccines, as well as research into creating an off-the-shelf product with shared new antigens that would allow patients to be vaccinated against all common mutations.

“As soon as we find the tumor, we could start vaccinating [the patient],” Marron said. “That would, potentially, significantly increase the response rates to these immune therapies, because you would give patients that much more potential to have a T-cell response that’s able to recognize their cancer and kill it.”