SNB-101 monotherapy has previously demonstrated encouraging activity among patients with pretreated small cell lung cancer.
Investigators have initiated dosing for the first patient enrolled on an international phase 1b/2 trial (NCT07391813) evaluating the investigational nanoparticle agent SNB-101 among patients with extensive-stage small cell lung cancer, according to a press release from the developer, SN Biosciences, Inc.1
The multi-center trial will be conducted at sites across the US and Europe, with an approximate population of 135 patients. SNB-101 will be assessed across 3 sequential stages, including a dose-escalation portion in phase 1b based on a 3+3 design to determine the maximum tolerated dose at 50 to 70 mg/m2. Additionally, phase 2a will involve an assessment of the optimal therapeutic dose, and phase 2b will proceed with dose expansion while investigating clinical activity across a broader patient population. Key efficacy end points in the phase 2 portion of the trial include objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
The trial’s advancement into phase 2 is supported by previous phase 1 results among patients who received SNB-101 in South Korea. These data showed a favorable safety profile, with no grade 3 or higher diarrhea events. Additionally, the disease control rate (DCR) was 83.3% among patients who received the agent at high doses, and the mean PFS was 6.3 months among those with SCLC. According to the press release, these data compare favorably with historical reports for later-line therapeutic options like lurbinectedin (Zepzelca) and topotecan (Hycamtin).
Following prior phase 1 results, the
In the phase 1b/2 trial, SNB-101, a nanoparticle formulation of SN-38, was administered via intravenous infusion.3 Across each cohort, patients were assigned to receive the agent at 50 or 80 mg/m2, 60 or 96 mg/m2, or 70 or 112 mg/m2 intravenously over 90 minutes on day 1 and 15 of each cycle.
Patients 18 years and older with cytologically or histologically confirmed SCLC that is locally advanced or metastatic and has progressed on or after prior standard therapy for advanced disease containing platinum-based therapy plus etoposide with or without atezolizumab (Tecentriq) or durvalumab (Imfinzi) not suitable for surgical resection were eligible for enrollment on the trial. Other eligibility criteria included having measurable or evaluable disease per RECIST v1.1 guidelines, a life expectancy of more than 12 weeks, an ECOG performance status of 0 or 1, and no major surgery or direct radiation therapy to a hematopoietic site within 4 weeks before baseline. Having adequate hematological, renal, and liver function was another requirement for study entry.
Those with homozygous variant alleles UGT1A1*28 or UGT1A1*6 confirmed via UGT1A1 genotype testing at screening, known or suspected intolerance of the main ingredient of any of the excipients of SNB-101, known or uncontrolled asymptomatic heart failure, or intestinal palsy or bowel obstruction were ineligible for enrollment on the trial. Patients were also unsuitable for study entry if they had clinically significant and uncontrolled congestive heart failure, multiple ascites or pleural effusion, or HIV positivity.
In addition to the ongoing assessments of SNB-101 monotherapy, investigators are expanding the development of the agent into combination regimens with other immunotherapies used in standard SCLC care. Developers are also expanding the evaluations of SNB-101 into other solid tumor indications, such as gastric and pancreatic cancers.
