Dose-finding Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SNB-101(SN-38) in Patients With Tumors

A Phase I, Open-Label, Dose-finding Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenously Infused SNB-101(as SN-38) in Patients With Advanced Solid Tumors

SNB-101 is a novel nano-particle formulation of SN-38, the active metabolite of irinotecan(CPT-11). Study SNB101P01 is a multicenter, open-label, dose escalation, phase 1 study of SNB 101 with its active ingredient SN-38, in participants with advanced solid tumors. Dose escalation will occur using a modified accelerated titration design (ATD).

All participants will receive SNB 101 in different cohorts. SNB 101 will be administered intravenously to participants on day 1 and day 15 of each 28 day treatment cycle until progressive disease, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.

A Safety Review Committee will determine dose escalation, de-escalation, and modification and the MTD/RP2D based on DLTs and other safety information.

Each participant will undergo a screening period, a treatment period, and a follow-up period. Participants will be followed until death, withdrawal of consent, or end of study, whichever occurs first.

During the treatment period, participants will receive SNB-101 (dose range: 5 mg/m2 to 50 mg/m2) intravenously on day 1 and day 15 of each 28 day cycle.

Dose reductions are permitted after the DLT observation period, which occurs during the first 28 days of treatment (cycle 1). Participants may permanently or temporarily (at the investigator's discretion) discontinue SNB-101. If a participant experiences a DLT or unacceptable toxicity, SNB-101 treatment should be interrupted until the observed toxicity returns to baseline or ≤ grade 1 toxicity. The start of the next cycle can be delayed up to 2 weeks at the investigator's discretion.

Inclusion Criteria:

• Patients with a histologically or cytologically confirmed, locally advanced or metastatic disease, has progressed after systemic standard of care treatment for advanced disease and is not suitable for complete surgical resection.
• Patients with measurable or evaluable disease consistent with Response Evaluation Criteria in Solid Tumors version 1.1.
• Patients ambulatory with an Eastern Cooperative Oncology Group performance score of 0 or 1.
• Patients with adequate hematological, renal, and liver function(CTCAE V5.0 grade 1 or lower).
• Patients with the life expectancy of 3 months or longer.

Exclusion Criteria:

• Patients homozygous for UGT1A1*28 or UGT1A1*6 alleles.
• Patients known or suspected intolerance or hypersensitivity to main ingredient or any of the excipients of SNB-101.
• Patients with unintentional weight loss >10% within 3 months prior to screening.
• Patients who are on dialysis.
• Patients who are positive for HIVs.
• Patients with a QT interval with Fridericia's correction outside of normal.
• Patients with intestinal palsy or bowel obstruction.
• Patients with chronic inflammatory bowel disease.
• Patients who may require administration of neuromuscular blockers, peripheral muscle relaxants, etc. during the study.
• Patients who may require lapatinib during the study.
• Patients who may require attenuated vaccine during the study.
• Patients who are taking any medication that in the judgement of the investigator could have an effect on the action of SNB-101.
• Patients unable to participate in the study as judged by the investigator.