BL0020, a novel tumor microenvironment (TME)-targeting nano-mediated polypeptide-drug conjugate (NMPDC), in patients with advanced solid tumors: Updated results from the small cell lung cancer (SCLC) subset of a phase 1 study.

Abstract

8095 Background: BL0020 is a novel polypeptide-drug nanoconjugate (~10 nm in size) composed of PEG-modified poly(amino acid), enzyme-responsive peptide linkers, and topoisomerase I inhibitor (Topo1i) payloads. It accumulates in the tumor microenvironment (TME), where payloads are continuously released by specific enzymes, penetrate tumor cells, and effectively induce cell death. BL0020 has shown promising efficacy in advanced SCLC. Here, we present updated results from the SCLC subset of an international Phase 1 study of BL0020 (NCT05886868). Methods: Patients with locally advanced/unresectable or metastatic SCLC received BL0020 injection (20 mg/m² or 25 mg/m² IV every three weeks) until disease progression, unacceptable toxicity, or withdrawal of consent. Results: As of November 30, 2025, 49 patients were enrolled. Treatment-related adverse events (TRAEs) were consistent with expected payload-related effects, primarily manageable hematological and gastrointestinal toxicities, with no new safety signals identified. Grade 3/4 TRAEs occurring in ≥10% of patients included neutropenia, decreased white blood cell count, and anemia. All SCLC patients had progressed after at least one prior platinum-based chemotherapy regimen, and 61% had received prior anti-PD-(L)1 therapy. The median number of prior lines of therapy was 2 (range: 1–6). Among 13 efficacy-evaluable SCLC patients, the disease control rate (DCR) was 100% and the objective response rate (ORR) was 84.6%, with a confirmed ORR of 76.9%. In addition, eight patients achieved >50% tumor shrinkage. Among SCLC patients with baseline brain metastases, both ORR and DCR were 100%, with brain lesions showing >50% shrinkage or complete disappearance. At a median follow-up of 12.58 months, median progression-free survival (mPFS) was 10.15 months (95% CI: 4.93, not reached), median duration of response (mDOR) was 8.18 months (95% CI: 3.54, not reached), and median overall survival (mOS) was 15.31 months (95% CI: 7.46, not reached). Conclusions: BL0020 monotherapy demonstrated a manageable safety profile and promising antitumor activity in patients with advanced SCLC who progressed after at least one prior platinum-based chemotherapy. The therapy showed a high response rate and potential for prolonged PFS compared with standard chemotherapy. Clinical trial information: NCT05886868 .