Gritstone posts 'one of the most potent immunogenic-responses for a neoantigen vaccine'

Early data out of former Fierce 15 winner Gritstone Oncology have been heralded as a big win for the early-stage biotech by analysts.

Presenting at the European Society for Medical Oncology Immuno-Oncology Congress in Geneva, cancer vaccine biotech Gritstone said its phase 1 test of immunogenicity data showed a “rapid, robust and consistent induction of large numbers of CD8+ T cells against multiple neoantigens in four solid tumor patients with available IFN-g ELISpot data (up to 3,000 IFN-g spot forming units per 106 PBMCs were generated, as measured by overnight ELISpot)” within the first two dosing cohorts.

"Importantly, these T-cells were also able to produce IL-2 and Granzyme B, demonstrating that they have cytotoxic potential," the company added, saying it could also stimulate the expansion of pre-existing T-cell populations.

The data focused in on three advanced cancer patients, including two gastroesophageal adenocarcinoma patients and one non-small cell lung cancer patient who had previously progressed on prior anti-PD-L1 therapy. From the second cohort, early data came out of one microsatellite-stable colorectal cancer patient. The biotech said safety was clean.

“We are thrilled to observe very robust, polyfunctional CD8+ T cells against predicted neoantigens even at the first dose level of our phase 1 study,” said Andrew Allen, M.D., Ph.D., co-founder, president and CEO of Gritstone.

“We view these preliminary results as important de-risking data, demonstrating the unprecedented immunogenicity of our heterologous prime/boost vaccine platform at its lowest dose, in combination with nivolumab. Pre-clinical data have shown a clear dose response where higher doses of the self-amplifying RNA boost vaccination, as well as the addition of anti-CTLA-4, further increase the number and function of CD8+ T cells.

“Notably, the starting dose of self-amplifying RNA was conservative since this is the first in-human study with this therapeutic approach. Therefore, we look forward to presenting mature data at higher doses with additional patients receiving the full immunotherapy regimen in several months.”

Analysts at SVB Leerink said the biotech had “reported one of the most potent CD8+ T-cell immunogenic-responses for a neoantigen vaccine in clinical trials, validating their hypothesis that a prime (chimpanzee adenovirus, ChAdV) and boost (self-amplifying RNA, SAM) approach would result in potent immune priming.” It did add, however, that excitement should be tempered given that there are only four patients.

Gritstone will report CD4+ helper T-cell responses, which SVB Leerink believes will be important for efficacy, in 2020, as well as clinical outcome data for a larger single-arm cohort.