legubicin (QHL-108) / Affinity Biopharma - LARVOL DELTA

Legubicin versus doxorubicin (DOX) in patients (pts) with advanced soft tissue sarcoma (STS): Results of randomized, phase II/III study (ESMO 2025) - "Conclusions This phase II/III trial demonstrated that legubicin achieved superior PFS and prolonged OS versus DOX in advanced STS, and a favorable safety profile in cardiac and hematologic toxicity, leading to clear reduction in toxicity and enhanced efficacy. It supports legubicin as a promising STS therapy with long-term maintenance treatment potential, and provides clinical proof for legumain-activated ALDC."

Clinical • Late-breaking abstract • Metastases • P2/3 data • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • LGMN

Phase 1b/2a Legubicin Trial, a Doxorubicin and Legumain-Cleavable Tetrapeptide Conjugate, for Pretreated Non-Small Cell Lung Cancer Patients (IASLC-WCLC 2026) - "Safety was evaluated according to NCI CTCAE 5.0. PT, preferred terms."

Clinical • P1/2 data • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • LGMN

Evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy Legubicin for Injection in patients with advanced malignant solid tumors. (ChiCTR) - P1 | N=30 | Recruiting | Sponsor: The East Hospital Affiliated to Tongji University; Shanghai Affinity Biomedical Technology Co., LTD

New P1 trial • Hepatocellular Cancer • Lung Cancer • Oncology • Solid Tumor

Safety, pharmacokinetics, pharmacodynamics and antitumor activity of legubicin in patients with advanced solid tumors, including lung cancer: a phase 1 dose-escalation and expansion trial. (PubMed, BMC Cancer) - "Legubicin is safe and well tolerated at a dose of 270 mg/m2 administered every 2 or 3 weeks, with preliminary signals of antitumor activities in a heterogeneous cohort of patients with pretreated advanced tumors, including heavily pretreated lung cancer patients. These findings support further evaluation in tumor‑specific studies."

First-in-human • Journal • P1 data • PK/PD data • Hematological Disorders • Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • LGMN

Novel ALDC and ADC with TMEAlinker and eribulin payload demonstrate excellent safety and efficacy in preclinical evaluation (AACR 2026) - "TMEAlinkers (TME-activated linkers) are legumain-activated linkers with clinical proof-of-concept (POC) from the phase 3 study of legubicin (an albumin drug conjugate, ALDC)...In cynomolgus monkeys, IMD2128 was well tolerated with a highest nonseverely toxic dose (HNSTD) over 16 mg/kg, showing a superior safety profile compared to VC linker-eribulin based ADCs (e.g., MORAb-202, HNSTD = 1.95 mg/kg). Pharmacokinetic studies in monkeys revealed a Cmax of 291.07 µmol/mL for IMD2128 ADC versus a Cmax of 0.0000823 µmol/mL for free eribulin (Cmax ratio ≈ 3.54 × 10⁶ : 1), confirming strong linker stability in circulation. Together, these findings highlight the versatility of the TMEAlinker platform for developing both ALDCs and ADCs with eribulin payloads, demonstrating excellent safety and efficacy in preclinical evaluations."

ADC • Preclinical • Oncology • Pancreatic Cancer • Solid Tumor • EGFR • LGMN • MET

Tumor microenvironment-activated T-cell engager (TMEA-TCE) targeting claudin 6 demonstrates efficacy without inducing cytokine release syndrome (AACR 2026) - "This activation strategy follows the same proof-of-concept demonstrated by the successful phase 3 studies of legubicin, an albumin-drug conjugate (ALDC). Pharmacokinetic studies in cynomolgus monkeys revealed high concentrations of IMD-1743 and minimal free TCE, indicating that the molecule is highly stable in circulation.In summary, these findings highlight a favorable therapeutic margin for IMD-1743 as a safe and effective TCE candidate targeting claudin 6. The strong preclinical efficacy combined with its tolerability profile supports further clinical development of IMD-1743 to address the significant unmet medical needs of patients with CLDN6-expressing tumors."

Biomarker • Clinical • Cytokine release syndrome • Tumor microenvironment • Gastric Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CLDN4 • CLDN6 • LGMN

Dual-payload TME-activated ADC platform (AACR 2025) - "Such advantageous characteristics of TMEA linkers could be supported by a TMEA-SMDC drug Legubicin in clinical trial that releases payload Doxorubicin...In various PBMCs-CDX models, dual-payload TMEA-ADCs such as IMD526 (HER2-ADC), IMD2126 (PD-L1-ADC) and IMD2113 (EGFR&TROP2-ADC) have displayed significant dose-dependent antitumor activities and induced complete tumor regressions with no observable toxicities. Compared to mono- or combo treatments with single-payload ADCs, IMD526 validated its superiority in the in-vivo CT26-HER+ syngeneic mouse model, and long-term elimination of detectable tumors was achieved with IMD526 both alone and combined with IMD101 (a TMEA-Cytokine releasing IL-2)...And different from the tumor cell endocytosis activation by GGFG-DXd ADCs, the bio-distribution of TMEA-ADCs resulted in faster and higher levels of payload accumulation in the tumor local tissues. In summary, by integrating antibody targeting, TME activation, cytotoxic therapy,..."

ADC • IO biomarker • Oncology • Solid Tumor • CTSS • EGFR • HER-2 • IL2 • LGMN • PD-L1 • PRKDC

A multicenter, open-label Ib/IIa phase clinical study evaluating the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of legobisone for injection in combination therapy in patients with advanced ovarian cancer and in patients with advanced recurrent/refractory choriocarcinoma treated with a single drug. (ChiCTR) - P1/2 | N=76 | Not yet recruiting | Sponsor: Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology; Shanghai Affinity Biomedical Technology Co., LTD

New P1/2 trial • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • BRCA

Biodistribution and preclinical safety profile of legubicin: A novel conjugate of doxorubicin and a legumain-cleavable peptide linker. (PubMed, J Appl Toxicol) - "However, cardiotoxicity was only noted at MTD dose levels. Altogether, our results confirm an improved safety profile of legubicin over conventional doxorubicin and support its clinical benefit for treating cancer."

Journal • Preclinical • Cardiovascular • Gastrointestinal Disorder • Oncology • LGMN

UHPLC-MS/MS Assay for Quantification of Legubicin, a Novel Doxorubicin-Based Legumain-Activated Prodrug, and Its Application to Pharmacokinetic and Tissue Distribution Studies. (PubMed, Molecules) - "Compared to administration of equimolar doses of doxorubicin, legubicin showed increased exposure of the active drug in the tumor and decreased the level of the active drug in the heart and kidney. This study provides valuable information on the pharmacokinetics and tissue distribution of legubicin, implicating its potential as a novel and effective drug candidate for anti-cancer therapies."

Journal • PK/PD data • Oncology • LGMN