GI Innovation Reveals Interim Clinical Results of 'GI-101' at SITC

Combination Clinical Trial with Keytruda 'KEYNOT-B59' Phase 1·2
GI Cell Also Reveals Nonclinical Data on Large-Scale NK Cell Culture Platform

Yoon Nari, Executive Director of Clinical Division at GI Innovation, is explaining the interim data of Phase 1 and 2 clinical trials of the immuno-oncology drug 'GI-101' from the KEYNOTE-B59 study at SITC2022 held in Boston, USA. (Photo by GI Innovation)

[Asia Economy Reporter Chunhee Lee] GI Innovation announced on the 14th that it revealed the interim results of the Phase 1/2 KEYNOTE-B59 clinical trial combining its immuno-oncology drug 'GI-101' with MSD (Merck & Co., USA)'s 'Keytruda' at the Society for Immunotherapy of Cancer 2022 (SITC 2022). Its affiliate GI Cell also disclosed nonclinical research data on its NK cell mass culture platform.

SITC is the largest annual conference in the field of immuno-oncology held in the United States. Experts in immuno-oncology research worldwide, global pharmaceutical companies, and oncology reviewers from the U.S. Food and Drug Administration (FDA) gather to share the latest developments in innovative drug development and clinical results. This year, it was held in Boston, USA, from the 8th to the 12th.

GI Innovation disclosed interim Phase 1/2 data, including preliminary efficacy and safety results of GI-101, from the ongoing KEYNOTE-B59 clinical trial involving approximately 375 solid tumor patients in Korea and the United States.

According to the clinical results, unlike other interleukin-2 (IL-2) competing products, GI-101 targets anticancer immune cells through CD80, allowing administration of a large amount of IL-2 without side effects. Even with dose escalation up to 0.3 mg/kg, which is about 10 to 50 times higher than competing products, no dose-limiting toxicity was observed. Adverse reactions commonly known to occur with IL-2 formulations, such as vascular leak syndrome and cytokine storm, were also absent. At dose escalation up to 0.3 mg/kg, an increase in anticancer immune cells CD8+ T cells and NK cells was observed compared to competing products, while there was no effect on the increase of immunoregulatory cells (Treg) that inhibit immune activation.

Notably, patients who showed confirmed partial responses (cPR) in both monotherapy and combination therapy were those who had previously been unresponsive to immuno-oncology treatments. This data confirms the potential of GI-101 as a drug to overcome resistance to immuno-oncology agents, which is emerging as the largest market.

Yoon Nari, Head of Clinical Division (Executive Director) at GI Innovation, stated, “Since terminal cancer patients participate in clinical trials after receiving all possible treatments, even well-known immuno-oncology drugs rarely show objective responses. The clinical results of GI-101, which showed a 46.6% tumor size reduction as monotherapy in immuno-oncology refractory bladder cancer patients, are encouraging.”

Jang Myungho, Chief Strategy Officer (CSO) of GI Innovation, also said, “The biggest concern for PD-1 antibody developers, who generate over 50 trillion KRW in global sales, is the reduced anticancer effect in patients lacking immune cells. GI-101 can sufficiently increase anticancer immune cells without toxicity, making it an ideal combination with PD-1 antibodies. Through the Keytruda combination therapy, this trial confirmed disease control in 75% of patients.”

The GI Cell research team is presenting the preclinical research results of T.O.P. NK at SITC 2022 held in Boston, USA. (Photo by GI Cell)

Meanwhile, GI Innovation’s affiliate GI Cell also announced that it presented nonclinical research data on the allogeneic natural killer (NK) cell therapy T.O.P. NK (Tumor targeting, Optimally Primed NK) at this year’s SITC.

GI Cell presented a poster titled “Nonclinical Research Results of T.O.P. NK Produced Using Cytokine Fusion Proteins Without Feeder Cells.” Generally, feeder cells are known to be necessary for mass culturing NK cells. However, GI Cell utilized its proprietary culture platform to mass-produce NK cells without feeder cells, enhancing both safety and manufacturing convenience.

The greatest advantage of T.O.P. NK cells is their ability to mass-produce activated NK cells from healthy donors without failure. Evaluation of receptor expression on T.O.P. NK cells showed high expression rates of activating receptors and specific chemokine receptors important for anticancer activity. In particular, CCR5 and CXCR4 were highly co-expressed, maximizing anticancer activity by targeting solid tumors.

Additionally, for commercialization of allogeneic NK cell therapies, GI Cell demonstrated its core cryopreservation technology. There was no significant difference in survival rate and activation marker expression of T.O.P. NK cells before and after freezing and thawing, proving the robustness of their cryopreservation technology.

Excellent anticancer activity was also confirmed in animal experiments. Data showed that intravenous administration of T.O.P. NK in humanized mice statistically significantly inhibited the growth of various solid tumors such as colorectal cancer, head and neck cancer, and breast cancer compared to control groups. Furthermore, toxicity tests conducted under Good Laboratory Practice (GLP) conditions showed no notable toxic reactions even at the highest doses.

Based on these nonclinical data, GI Cell submitted an Investigational New Drug (IND) application to the Korean Ministry of Food and Drug Safety in September for a Phase 1 clinical trial targeting solid tumor and hematologic cancer patients in Korea. The trial will evaluate the safety, tolerability, and efficacy of T.O.P. NK.

Hong Chunpyo, CEO of GI Cell, said, “At this SITC, despite the development of many cell therapies, we confirmed an unmet demand for cell therapies capable of mass production. Based on our research results, we plan to enter clinical trials early next year and do our best to ensure that many patients with intractable terminal cancers can benefit from immune cell therapies as soon as possible.”

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