STCube's 'Nelmastobat' Shows Highest Ever Response Rate in Phase 4 Colorectal Cancer Trial: "ORR 21%"

STCube is demonstrating clinical results far superior to standard treatments in metastatic colorectal cancer patients who have undergone third-line or later therapies, setting a new record for the best treatment outcomes to date.

On the 20th, STCube announced updated results from the investigator-initiated Phase 1b/2 study of Nelmastovat combined with Capecitabine as a third-line treatment for metastatic colorectal cancer.

Interim data showed that among 19 patients with completed tumor evaluations, there were 4 partial responses (PR) and 13 stable disease (SD) cases, resulting in an objective response rate (ORR) of 21%. Since the previous Phase 1b results (12 patients), an additional 7 patients were evaluated, revealing 2 more PRs and 3 SDs. The progression-free survival (PFS) of patients is also reported to be extending beyond the target threshold.

The patients enrolled in the trial were those with MSS (microsatellite stable) colorectal cancer, known to have low response rates to immunotherapy. All 4 PR patients had MSS colorectal cancer with KRAS or BRAF mutations, which generally have poorer prognoses than typical metastatic colorectal cancer patients; among them, 2 patients had liver metastases.

Currently, no immunotherapy has proven efficacy in colorectal cancer. Pembrolizumab (Keytruda) is used only in about 5% of patients with MSI-H (microsatellite instability-high) colorectal cancer, while the remaining 95% of MSS patients receive no therapeutic benefit.

▲ Pembrolizumab monotherapy showed an ORR of 0% (0/18) and failed to demonstrate efficacy in Phase 2 MSS colorectal cancer trials. ▲ The combination of immunotherapy and chemotherapy agents, such as Nivolumab (Opdivo) and Regorafenib, showed an ORR of 7% (5 PRs among 70 patients without liver metastases), median progression-free survival (mPFS) of 1.8 months, and median overall survival (mOS) of 11.9 months in Phase 2 MSS colorectal cancer trials, failing to meet the primary endpoint of ORR.

The ORRs of chemotherapy agents currently used as standard third-line treatments are mostly around 1%. The mPFS and mOS are also approximately 2 months and 6 months, respectively. In this challenging treatment environment, last year, the combination of chemotherapy and targeted therapy agents TAS-102 and Bevacizumab demonstrated significant efficacy in a Phase 3 trial with an ORR of 6.1%, mPFS of 5.6 months, and mOS of 10.8 months, leading to FDA approval.

Professor Suhyun Lee of Korea University Anam Hospital’s Department of Oncology, who is conducting this study, stated, “Through Phase 1b, we determined the recommended Phase 2 dose (RP2D) without additional toxicity, and currently, in the ongoing Phase 2 study, 2 more patients have reported PRs.” He added, “The Nelmastovat-Capecitabine combination therapy has proven safety as no additional toxicity beyond the known toxicities of Capecitabine occurred.” He further noted, “So far, a high response rate of over 20% and treatment maintenance for more than 4 months in over half of the patients have been observed, suggesting that this therapy is expected to achieve outcomes surpassing standard treatments.”

Jung Hyunjin, CEO of STCube, said, “The clinical progress has exceeded expectations, and we have high internal hopes.” He emphasized, “Along with the ORR indicator, PFS, which represents the duration patients survive without disease progression, must also be considered. Currently, patients’ PFS is confirmed to be better than existing treatments, and most importantly, terminal cancer patients are maintaining their daily lives without suffering from chemotherapy side effects, which is a very meaningful therapeutic effect.”

He continued, “The anticancer efficacy observed in difficult-to-treat stage IV colorectal cancer patients, including those with MSS, liver metastases, and KRAS or BRAF mutations, has elicited remarkable responses in clinical settings.” He added, “Since the correlation between BTN1A1 expression levels and Nelmastovat treatment efficacy has been directly demonstrated in patients, conducting clinical trials using BTN1A1 as a biomarker is expected to yield even more innovative results.”

STCube is currently preparing company-initiated clinical trials (SIT) and pursuing strategic partnerships with colorectal cancer as the indication.