Latest advances in immunotherapy from SITC 2023

T cell attacking cancer cell

The Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting (SITC 2023) took place on 1-5 November 2023, at San Diego Convention Center in San Diego, US.

CAN-2409 in non-metastatic pancreatic cancer

Candel Therapeutics reported on initial positive interim data from its Phase II clinical trial of CAN-2409 that showed notable improvements in patients with borderline resectable pancreatic ductal adenorcarcinoma (PDAC).

The estimated overall survival rate was 71.4% at 36 months in CAN-2409 treated patients versus 16.7% in the control arm after chemoradiation.

Dense aggregates of immune cells, including CD8 positive granzyme B positive cytotoxic T cells, dendritic cells, and B cells, were observed in PDAC tissue after CAN-2409 treatment, confirming activation of a robust antitumoral immune response.

“Given frequent recurrence and short survival with SoC chemotherapy for non-metastatic PDAC, effective new treatment options are urgently needed,” said Garrett Nichols, MD, MS, Chief Medical Officer of Candel. “We are encouraged by the improved survival associated with CAN-2409 for the treatment of borderline resectable PDAC, demonstrated for the first time in a randomised clinical trial. CAN-2409 was generally well tolerated without significant additional local or systemic toxicity when added to SoC chemoradiation.”

SNS-101, VISTA-blocking monoclonal antibody

Sensei Biotherapeutics presented clinical dose escalation data from a Phase I/II study of its SNS-101 monotherapy, which showed well tolerated safety profile, potentially best-in-class pharmacokinetics, and encouraging cytokine release profile across multiple dose cohorts.

It is the first VISTA-blocking antibody administered at a dose anticipated to be therapeutically relevant without eliciting dose-limiting toxicity.

“The data support that this highly innovative antibody is well tolerated across dose levels tested to date, shows linear, dose-dependent pharmacokinetics predicted preclinically to elicit immune-mediated anti-tumour activity, and a cytokine profile consistent with an absence of cytokine release syndrome,” said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics.

“Data from this clinical study to date provides important initial evidence that SNS-101 can provide clinically meaningful and mechanistic differentiation from first generation anti-VISTA approaches, as indicated by SNS-101 dose levels that are at least 10 times higher than the first clinical study of a competitor VISTA antibody that was prematurely halted due to cytokine release syndrome and poor pharmacokinetics.”

STK-02, IL-12 partial agonist

Synthekine presented new data from preclinical studies of STK-026, a biased IL-12 agonist engineered to exhibit preferential activity on antigen-activated T cells, which drive the efficacy of IL-12, while avoiding broad systemic activation of resting T cells and NK cells, which are linked to the toxicity of IL-12.

Overall, assessments of STK-026 in mouse and cyno show that its properties successfully avoid spikes of early NK activation but still effectively activate T cells, the company reported.

“In the quest for developing new and effective cancer treatments, the pro-inflammatory cytokine IL-12 has shown tremendous potential but clinical use of IL-12 is limited by systemic toxicities and a very narrow therapeutic window,” said Martin Oft, Chief Scientific Officer of Synthekine. “The data presented today adds to the growing body of evidence that STK-026’s novel approach, biasing IL-12’s activity toward activated T cells and avoiding hyperactivation of NK cells, has potential to harness anti-tumour efficacy without dose-limiting toxicity.”

HB-200 in head and neck cancer

In Phase I data presented at SITC 2023, HOOKIPA’s HB-200 monotherapy induced a robust increase in circulating tumour-specific CD8+ T cells in all evaluable patients with heavily pretreated HPV16+ head and neck cancer.

In 29 of 35 patients, T cell increases were rapid and sustained for at least eight months, and T cell function improved over time with repeat dosing.

Paired biopsy data from 13 heavily pre-treated patients showed that patients who achieved disease control after treatment with HB-200 monotherapy generally had greater CD8+ T cell infiltration in tumours and the tumour microenvironment compared to patients with a best overall response of disease progression.

“The data presented at SITC expand the body of evidence that HB-200 monotherapy has the ability to induce targeted T cells necessary for tumour control, which can translate into tumour shrinkage and encouraging clinical activity, especially in a difficult-to-treat population,” said Joern Aldag, Chief Executive Officer at HOOKIPA. “As the data have matured, we have consistently delivered best-in-class T cell activation, and we continue to see the durability and functionality of tumour-specific T cells induced by HB-200. We look forward to sharing continued analyses of HB-200 across all arms of our trial in the future.”

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