What does this research mean for the field?

Single protein encapsulation of the TOP1 inhibitor SN38 (SPESN38-5/8) creates a water-soluble formulation with superior pharmacokinetics, lower toxicity, and greater antitumor efficacy in mouse models compared to irinotecan and doxorubicin. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

What question did this study set out to answer?

The study aims to evaluate the efficacy and toxicity of SPESN38-8, a novel formulation of SN38 for cancer treatment.

May 30, 2026

Efficacy and toxicity of the antitumor agent SPESN38-8.

Key Points

The study aims to evaluate the efficacy and toxicity of SPESN38-8, a novel formulation of SN38 for cancer treatment.
Utilized a patented single protein encapsulation platform to create SPESN38-5/8 complexes from SN38 and human serum albumin (HSA).
Conducted pharmacokinetic analysis and in vitro/in vivo efficacy evaluations against various cancer models.
Evaluated maximum tolerated dose (MTD) and compared effects with irinotecan and doxorubicin in multiple models.
SPESN38-8 complexes dissolved in water, achieving a plasma AUC for SN38 significantly higher than irinotecan.
In in vitro tests, SPESN38-8 demonstrated IC50 values significantly lower than those of irinotecan, showing superior inhibitory effects.
In vivo efficacy studies resulted in complete tumor eradication in multiple cancer models with significantly improved outcomes compared to standard therapies.

Abstract

e15528 Background: SN38 as TOP1 inhibitor is a potent anticancer agent; however, poor water solubility prohibited its direct clinical applications. Only prodrug approach on SN38 has resulted in 2 types of drugs, irinotecan and sacituzumab govitecan. Furthermore, poor enzymatic conversion (2–8%) of irinotecan into active metabolite SN38 severely limits its efficacy. Numerous attempts on drug delivery systems have failed. Therefore, novel approaches are urgently needed for effectively delivering SN38. Methods: Our patented single protein encapsulation (SPE) platform, allowing encapsulation of small-molecule drugs by a single protein (albumins or globulins) without artificial nanoparticles and chemical modifications to drugs and proteins, has made SPEDOX-6 into human phase IB/IIA clinical trial (NCT0764018). Great success of SPEDOX-6 prompted us to utilize same SPE technology for encapsulation of SN38 by HSA to create SPESN38-5/8 complexes, which were well characterized by membrane dialysis, HPLC, UV led to 8/8 mice tumor free on Day 21, which were monitored for total 230 days, tumor relapse wasn’t found for > 209 days, indicative of cancer eradication; (2) A204, SPESN38-8 at 35 mg/kg vs doxorubicin at 4.0 mg/kg, led to all 4 females free of tumor (4) HCT-116 (colorectal cancer) model, SPESN38-5 at 55 mg/kg vs irinotecan at 50 mg/kg, SPESN38-5 was much effective to suppress HCT-116 than irinotecan; (5) A549, SPESN38-8 at 35 mg/kg vs irinotecan at 50 mg/kg, SPESN38-8 was extremely effective to inhibit A549 than irinotecan. Conclusions: SPESN38 complexes provide a novel water soluble SN38 formulation. SPESN38-5 & SPESN38-8 demonstrate better PK values, lower toxicity and superior antitumor efficacy in mouse models, compared with irinotecan, DOX & doxorubicin. FDA has green-lighted SPESN38-8 (IND #: 164346) for clinical development.

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