Immuno-oncology developer STCube announced on the 5th that it has received the final Clinical Study Report (CSR) for the global Phase 1 clinical trial of the anti-BTN1A1 immune checkpoint inhibitor ‘Nelmastobat (hSTC810).’ As the first-in-class immuno-oncology agent, it demonstrated excellent safety, scientific mechanism of action, and efficacy of the anti-BTN1A1 therapy.
In 2022, STCube conducted a multinational, multicenter, multiple-dose, open-label, dose-escalation Phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of Nelmastobat monotherapy in 47 patients with advanced solid tumors. This was the first human clinical trial of Nelmastobat.
The subjects were terminal cancer patients who had failed more than three prior anticancer treatments, mostly representing ‘Cold Tumors’?tumors resistant to immuno-oncology therapies?such as colorectal cancer, small cell lung cancer, and ovarian cancer. Cold tumors lack immune cells, making them unresponsive to conventional immuno-oncology drugs.
Patients received Nelmastobat every two weeks, with six dose escalation levels (0.3mg/kg, 1mg/kg, 3mg/kg, 6mg/kg, 10mg/kg, 15mg/kg) and a dose expansion cohort. Clinical trial sites included the MD Anderson Cancer Center, Yale Cancer Center, Mount Sinai Hospital in the U.S., as well as Severance Hospital in Sinchon and Korea University Anam Hospital in Korea.
As a result, Nelmastobat showed excellent outcomes in the primary endpoints of safety and tolerability. No dose-limiting toxicities (DLTs) occurred in all subjects (47 patients) or at the maximum dose (15mg/kg), and the maximum tolerated dose (MTD) was not reached.
Regarding treatment-emergent adverse events (TEAEs), most were mild adverse events (AEs) such as grade 1 or 2 fatigue and decreased appetite, with no drug-related deaths. Treatment-related adverse events (TRAEs) occurred in 24 patients (51.1%), but most were mild grade 1 or 2 AEs. Clinically significant grade 3 or higher TRAEs were observed in only one patient (2.1%).
An STCube representative stated, “Having demonstrated top-level safety in Phase 1, the safety results alone sufficiently prove the value of Nelmastobat as a new anticancer drug. Despite targeting cold tumors and heterogeneous patient groups known to be difficult to treat with immuno-oncology agents, elucidating the clear mechanism of action and anticancer activity of the anti-BTN1A1 therapy in humans is a very meaningful outcome.”
In terms of efficacy, notable findings were observed in small cell lung cancer and colorectal cancer, which are currently undergoing follow-up clinical trials.
Among the small cell lung cancer patients participating in Phase 1, analysis of three patients eligible for efficacy evaluation showed that treatment response varied significantly depending on BTN1A1 expression. Two patients with high BTN1A1 expression showed stable disease (SD) as a treatment response, while one patient with low BTN1A1 expression was classified as having progressive disease (PD). The SD patient, who continues treatment under compassionate use approval, has recorded a progression-free survival (PFS) of over 1 year and 6 months (20 months), which is remarkable for small cell lung cancer where long-term survival is difficult to expect.
Additionally, notable mixed responses were observed in various patients after treatment completion. For example, a stage 4 colorectal cancer patient with liver metastasis (dose 0.3mg/kg) was evaluated as PD during treatment but showed a partial response (PR) after receiving chemotherapy (capecitabine) post-treatment. Since this patient had not responded to chemotherapy previously, this effect is analyzed as a result of combination therapy with Nelmastobat.
In February this year, STCube initiated Phase 1b/2 clinical trials of Nelmastobat combined with chemotherapy for extensive-stage small cell lung cancer and investigator-initiated Phase 1b/2 trials for metastatic colorectal cancer. Early results from the colorectal cancer investigator-initiated Phase 1b trial showed a disease control rate (DCR) of 100% and an objective response rate (ORR) of 16.7%, surpassing the DCR, ORR, and PFS of existing third-line or later standard treatments.
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