First Ever Phase 1B Trial of NK Cells with IL-2 and VACTOSERTIB

On June 24, 2022 Chimeric Therapeutics Ltd (ASX:CHM) reported the first ever trial studying NK cells in combination with IL-2 and Vactosertib, using Chimeric’s CORE NK platform cells (Press release, Chimeric Therapeutics, JUN 24, 2022, View Source [SID1234616225]).

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The Phase 1B investigator-initiated trial has been approved by the US Food and Drug Administration (FDA) and will enrol 12 patients at UH Seidman Cancer Center in Ohio, with either locally advanced or metastatic colorectal cancer or relapsed/refractory blood cancers.

Chimeric’s CORE NK platform is a novel NK cell therapy platform of ex-vivo expanded non-HLA*-matched universal donor NK cells.

Safety and early efficacy demonstrated
The CORE NK platform was studied in a Phase 1A clinical trial demonstrating safety and an early efficacy signal in patients with metastatic colorectal cancer and refractory haematological malignancies.

The new study seeks to build upon responses observed during the initial CORE NK clinical trial, by co-administering the CORE NK cells with subcutaneous IL-2 and oral Vactosertib.

Study looks at combination
IL-2 is known to activate NK cells by stimulating proliferation and enhancing function.

Vactosertib is an oral TGF-β receptor inhibitor that can potentially disrupt the TGF-β signalling pathway, which has been shown to limit the effectiveness of immune therapies like NK cells.

"Vactosertib has never been used in combination with NK cells in the clinic, but it has been used in humans in other clinical trials," said UH Seidman oncologist Dr J Eva Selfridge, assistant professor at Case Western Reserve University School of Medicine in Ohio, who will lead the upcoming trial.

NK cells can "actually make it into the tumours"
"The goal of using it in this trial is to disrupt the TGF-β signaling pathway that is so strong in colorectal cancer and cells. We want to shut down that TGF-β signaling pathway so that the NK cells can actually make it into the tumours. Once they’re there, they have a chance of being active instead of just being silenced right away."

Dr. Selfridge says she is hopeful this new clinical trial at UH Seidman Cancer Center will present patients with more and better options for treatment and care: "T cell-directed immunotherapy is only available for 5% or less of cancer patients, but immunotherapy is really the only way we have to cure people with metastatic disease," she said.

"We’re just beginning our study, but ultimately the goal is to find immune therapies that work long-term."

Busy clinical pipeline
The study adds to CHM’s busy clinical pipeline, with now four clinical trials in progress or planned within 9 months.

"With the initial positive results seen in the Phase 1A clinical trial with our CORE NK Platform cells, we have been eager to accelerate the development opportunities for it," said Chimeric CEO Jennifer Chow.

"This study looks to combine novel therapeutics to overcome the challenges that are commonly thought to limit disease responses to NK cells.

"We hope that this combination will allow us to see more complete responses in patients with difficult to treat diseases, like the one seen in the Phase 1A study that has resulted in complete tumour eradication for more than 15 months now."