Chimeric Therapeutics Ltd (ASX:CHM) has released the results of the Phase 1 clinical trial of its CORE NK platform – a clinically validated, off-the-shelf, robust, enhanced natural killer cell platform – conducted at Case Comprehensive Cancer Center.
“We are incredibly excited to share the data as we believe that it demonstrates the transformational potential for our CORE NK platform,” CEO Jennifer Chow said.
“By establishing safety without GvHD, substantial efficacy with a highly durable CR, robust ex vivo expansion and promising persistence of cells without exogenous cytokine support we now have a strong foundation upon which to amplify our therapeutic efficacy.
"We look forward to rapidly advancing the multiple development paths planned for CORE NK in both blood cancers and solid tumours.”
Over the course of the trial, nine heavily pre-treated patients, three with blood cancers and six with solid tumours, were administered two infusions at one of three different CORE NK dose levels.
Blood cancer patient results
The results saw all three of the patients with blood cancers achieve a best response of stable disease at day 28. One of the patients achieved a complete response (CR) by the 100-day assessment.
This patient received an allogeneic transplant as a consolidation therapy and more than 15 months later remains in remission.
Of the other two patients who achieved stable disease at day 28, one had progressed by day 100 while the other maintained their disease stability.
Solid tumour patients
Of the six patients with solid tumours – colorectal cancer and colon cancer – treated with Chimeric’s CORE NK, a 33% disease control rate (DCR) was demonstrated, with two of the six patients achieving a best response of stable disease by day 28.
One of the two patients who had achieved stable disease at day 28 maintained their disease stability at day 100.
Safety first
The primary objective of the trial was safety – “to demonstrate that escalating doses of off-the-shelf NK cell products generated on the NKF expansion platform from third-party adult donors can be infused without inducing graft-versus-host (GvHD) or other significant toxicities”.
The company says the secondary goals of the study were to examine if the administered regimen would prevent immediate rejection of the HLA-mismatched NK cell product, thereby allowing for demonstrable anti-tumour effect. All patients tolerated CORE NK well, with no dose limiting toxicities, no cytokine release syndrome and no GvHD disease.
All observed events were expected events attributable to the lymphocyte-depleting chemotherapy regimen.
The CORE NK cells are ex vivo expanded 'universal donor' NK cells that use a novel feeder cell line (NKF) generated through the expression of membrane-bound interleukin 21 (mbIL-21) on the acute myeloid leukemia cell line, OCI-AML3.
The CORE NK cell products generated using this novel feeder cell platform exhibited in vivo persistence for four weeks promoted by preparative lymphodepletion alone in the Phase 1 clinical trial.
What next?
Chimeric is now advancing the development of its CORE NK platform with plans to increase the administered NK cell doses, provide optimised exogenous cytokine support or other complementary agents and promote tumour bed infiltration in solid tumours through the development of CAR NK therapies.
“The data from our Phase 1 study are extremely encouraging, demonstrating an optimal safety profile and strong early signs of clinical benefit for patients, said study investigator David Wald, MD, PhD.
"I look forward to collaborating with Chimeric to continue advancing this program for blood cancers and to further optimise the platform for solid tumours through the incorporation of specific CARs and other enhancements."
Wald – who is associate professor of Pathology Case Western Reserve University School of Medicine; member, Immune Oncology Program, Case Comprehensive Cancer Center; and associate director for Basic Research, University Hospitals, Wesley Center for Immunotherapy – invented the NKF technology.
In November 2021, Chimeric secured the exclusive option to license the NKF technology from Case Western Reserve University.
Chimeric is advancing development of its CORE NK Platform as a combination therapy in blood cancers and as chimeric antigen receptor (CAR) NK therapies in solid tumours.