FDA Grants Fast Track Designation to SNB-101 in Small Cell Lung Cancer

Treatment with SNB-101 previously demonstrated tolerability among patients with solid tumors in a phase 1 trial.

The FDA has granted fast track designation to SNB-101, an anti-cancer agent derived from SN-38 as nanoparticles, as a treatment for patients with small cell lung cancer (SCLC), according to a press release from the developers, SN Bioscience.¹

As part of the fast track designation, developers may apply for the accelerated approval of SNB-101 in the aforementioned indication following the completion of phase 2 clinical trials. Additionally, it may be possible for the agent to earn priority review after the completion of phase 3 trials.

Investigators have completed a phase 1 trial (NCT04640480) evaluating treatment with SNB-101 in patients with different advanced solid tumors. Findings from this trial were previously presented at the 2023 European Society for Medical Oncology (ESMO) Congress.

With a cutoff date of April 28, 2023, the objective response rate (ORR) among 21 evaluable patients was 14.3%.² Additionally, the disease control rate (DCR) was 42.9%. Investigators highlighted partial responses (PRs) in 3 patients with SCLC, non–small cell lung cancer (NSCLC), and rectal cancer. Treatment with SNB-101 elicited a median progression-free survival (PFS) and overall survival (OS) of 1.9 months and 6.1 months, respectively.

Common treatment-related adverse effects (TRAEs) included neutropenia (61.9%), white blood cell count decreases (28.6%), nausea (23.8%), anemia (19.0%), and platelet count decreases (19.0%). Grade 3/4 toxicity included neutropenia (33.3%), white blood cell count decreases (14.3%), and platelet count decreases (9.5%). Following dose escalation across all planned dose levels, the maximum tolerated dose was not reached.

“SNB-101 was well tolerated; despite relatively high rates of hematological AEs, neutropenia was manageable. SNB-101 demonstrated antitumor efficacy, which appeared to be dose dependent,” the study authors wrote.2 “A phase 1b/2a trial combining SNB-101 with immunotherapy is planned.”

In this open-label, dose-finding phase 1 study, patients were assigned to receive SNB-101 at various escalating doses.³ Doses ranged from 5 mg/m² intravenously every 2 weeks to 50 mg/m² intravenously every 2 weeks across the trial’s cohorts.

The trial’s primary end points included dose-limiting toxicities, treatment discontinuation following AEs, clinically meaningful changes in vital signs from baseline, and electrocardiogram results. Secondary end points included ORR, DCR, OS, PFS, and time to progression.

Patients 19 years and older with histologically or cytologically confirmed locally advanced or metastatic disease that has progressed following standard systemic therapy for advanced disease were eligible for enrollment on the trial. Additional eligibility criteria included having measurable or evaluable disease per RECIST v1.1 guidelines; an ECOG performance status no higher than 1; adequate hematological, renal, and liver function; and a minimum life expectancy of 3 months.

Those with known or suspected intolerance of the main ingredient of SNB-101 or unintentional weight loss of more than 10% within 3 months of screening were ineligible for enrollment. Patients were also unsuitable for study entry if they had a QT interval with Fridericia's correction outside of normal, bowel obstruction or intestinal palsy, chronic inflammatory bowel disease, or therapy with attenuated vaccines during study treatment. Requiring treatment with neuromuscular blockers, peripheral muscle relaxants, or similar agents during the study was also grounds for exclusion from the trial.

According to the press release, developers plan to expand research with SNB-101 in other solid cancer types, which include colon cancer, gastric cancer, and biliary tract cancer.

The FDA previously granted orphan drug designation to SNB-101 for managing SCLC in July 2023.⁴ Additionally, the regulatory agency granted orphan drug designation to the agent for treating patients with pancreatic cancer in February 2024.⁵

References

1. SN Bioscience receives FDA fast track designation for small cell lung cancer. News release. SN Bioscience Co. Ltd. May 9, 2024. Accessed May 10, 2024. https://tinyurl.com/eenb6zkk
2. Sang YB, Kim Y, Lee MA, et al. Preliminary findings from a phase I, open-label, dose-finding study of SNB-101 in patients with advanced solid tumors. Ann Oncol. 2023;34(suppl 2):S474. doi:10.1016/j.annonc.2023.09.1863
3. Dose-finding study to evaluate the safety, tolerability, and pharmacokinetics of SNB-101 (SN-38) in patients with tumors. ClinicalTrials.gov. Accessed May 10, 2024. https://tinyurl.com/yst6nrmt
4. US FDA grants orphan drug designation of SN Bioscience's nano anti-cancer drug 'SNB-101' for small cell lung cancer. News release. SN Bioscience Co. Ltd. July 20, 2023. Accessed May 10, 2024. https://tinyurl.com/5y2y3cuh
5. SN BioScience received US FDA orphan drug designation for its nano anti-cancer drug 'SNB-101' on pancreatic cancer. News release. SN Bioscience Co. Ltd. February 29, 2024. Accessed May 10, 2024. https://tinyurl.com/46ujuj6v