firtecan pegol (PEG-SN38) / Zhejiang Hisun, Belrose - LARVOL DELTA

Evaluating pegylated SN38 (PLX38A) and rucaparib in TP53 wild-type endometrial cancer. (ASCO 2025) - "These findings suggest that the combination of rucaparib and SN38 (PLX038A) is effective in EC primary patient tumor organoids and PDXs with wild-type TP53. No significant negative physiological effects on animal TCS and weight change were observed. No drug-related toxicity was observed in mice receiving combination treatment."

Endometrial Cancer • Obesity • Oncology • Solid Tumor • TOP1 • TP53

Antitumor activity of rucaparib plus PLX038A in serous endometrial carcinoma. (PubMed, J Exp Clin Cancer Res) - "Collectively, these studies identify a set of genomically characterized PDX models for preclinical testing of potential SEC therapies and a therapeutic combination that warrants further preclinical investigation."

Journal • Endometrial Cancer • Oncology • Solid Tumor • HRD • RAD51

PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers (clinicaltrials.gov) - P1/2 | N=10 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Feb 2025

Trial completion • Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers (clinicaltrials.gov) - P1/2 | N=10 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

PLX038 for Treatment of Metastatic Platinum-resistant Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=43 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Feb 2025 ➔ Dec 2031 | Trial primary completion date: Feb 2025 ➔ May 2027

Metastases • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • TOP1

TOPOLOGY: A phase II study to evaluate the efficacy and toxicities of PLX038, in patients with locally advanced or metastatic triple-negative breast cancer. (ASCO 2024) - P2 | "Background: Sacituzumab govitecan (SG) is an anti-TROP2 antibody-drug conjugate (ADC) with an SN-38 payload (topoisomerase I inhibitor) that was recently approved for use in advanced triple-negative breast cancer (TNBC)...PLX038 is a 40 kDa 4-arm PEG-SN38 conjugate with a half-life of 5 days...A Simon's two-stage optimum design will be used, and a maximum of N=44 patients will be included, 1. Santi et al., Biodrugs 2024."

Clinical • Metastases • P2 data • Breast Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • Triple Negative Breast Cancer • RB1

PLX038 for Treatment of Metastatic Platinum-resistant Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=43 | Recruiting | Sponsor: Mayo Clinic | Trial primary completion date: Feb 2024 ➔ Feb 2025

Metastases • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • TOP1

PLX038 for Treatment of Metastatic Platinum-resistant Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=43 | Recruiting | Sponsor: Mayo Clinic | Suspended ➔ Recruiting

Enrollment open • Metastases • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • TOP1

PLX038 for Treatment of Metastatic Platinum-resistant Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=43 | Suspended | Sponsor: Mayo Clinic | N=31 ➔ 43

Enrollment change • Metastases • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

Preparation of an Ultrahigh-DAR PDL1 monoclonal antibody-polymeric-SN38 conjugate for precise colon cancer therapy. (PubMed, Biomaterials) - "The bonding of Fc-III-4C peptide with PLG-graft-mPEG/SN38 (Fc-NPLG-SN38) was achieved using a click reaction between azide and DBCO groups...aPDL1-NPLG-SN38 exhibited excellent therapeutic properties in both medium-sized and large MC38 tumor animal models. The present study provides the details of a novel preparation strategy for SN38-loaded ADCs having a high DAR."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

PLX038 for the Treatment of Patients With Platinum-resistant Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=31 | Suspended | Sponsor: Mayo Clinic | Active, not recruiting ➔ Suspended

Trial suspension • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

PLX038 for the Treatment of Patients With Platinum-resistant Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=31 | Active, not recruiting | Sponsor: Mayo Clinic | Recruiting ➔ Active, not recruiting

Enrollment closed • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers (clinicaltrials.gov) - P1/2 | N=10 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | N=65 ➔ 10

Enrollment change • Enrollment closed • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

PLX038 for the Treatment of Patients With Platinum-resistant Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=31 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting

Enrollment open • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

Pulmonary delivery of liposomes co-loaded with SN38 prodrug and curcumin for the treatment of lung cancer. (PubMed, Eur J Pharm Biopharm) - "SN38 was linked to cell-penetrating peptide (CPP) TAT via a polyethylene glycol (PEG) linker to form the SN38 prodrug (TAT-PEG-SN38)...The combination induced significant tumor inhibition in a BALB/c mouse lung cancer model. These results indicated that our SN38 prodrug and curcumin co-delivery system was a promising candidate for lung cancer treatment."

Journal • Lung Cancer • Oncology • Solid Tumor

PLX038 for the Treatment of Patients With Platinum-resistant Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=31 | Not yet recruiting | Sponsor: Mayo Clinic

New P2 trial • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

Study of EZN-2208 Pediatric Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=32 | Terminated | Sponsor: Enzon Pharmaceuticals, Inc. | N=24 ➔ 32 | Active, not recruiting ➔ Terminated; Program suspended and divested

Enrollment change • Trial termination • Oncology • Pediatrics • Solid Tumor

PEG-SN38: A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=160 | Terminated | Sponsor: Enzon Pharmaceuticals, Inc. | Active, not recruiting ➔ Terminated; Program suspended and divested

Trial termination • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2

A Nanotherapeutic Strategy to Overcome Chemoresistance to Irinotecan/7-Ethyl-10-Hydroxy-Camptothecin in Colorectal Cancer. (PubMed, Acta Biomater) - "As the first nano-formulation of Ko143 and the first systemic co-delivery vehicle of SN38/CPT-11 and a BCRP inhibitor, BI@PEG-SN38 provides a new strategy for clinical development of SN38 and numerous "chemosensitizers", and exhibits promising applicability in precision cancer medicine. Panels of cancer cell lines established here provides a useful platform for BCRP- and cancer-related research and technology development."

Journal • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers (clinicaltrials.gov) - P1/2; N=10; Suspended; Sponsor: National Cancer Institute (NCI); N=65 ➔ 10; Recruiting ➔ Suspended

Enrollment change • Trial suspension • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • BRCA

PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers (clinicaltrials.gov) - P1/2; N=62; Recruiting; Sponsor: National Cancer Institute (NCI); Trial completion date: Dec 2022 ➔ Dec 2024; Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Prospective use of the single-mouse experimental design for the evaluation of PLX038A. (PubMed, Cancer Chemother Pharmacol) - "This study demonstrates the feasibility of using a single-mouse design for assessing the antitumor activity of an agent, while encompassing greater genetic diversity representative of childhood cancers. PLX038A was highly active in most xenograft models, and tumor sensitivity to PLX038A was correlated with sensitivity to irinotecan, validating the single-mouse design in identifying agents with the same mechanism of action. Biomarkers that correlated with model sensitivity included wild-type TP53, or mutant TP53 but with a mutation in 53BP1, thus a defect in DNA damage response. These results support the value of the single-mouse experimental design."

Journal • Ewing Sarcoma • Oncology • Pediatrics • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Wilms Tumor

PLX038: a PEGylated prodrug of SN-38 independent of UGT1A1 activity. (PubMed, Cancer Chemother Pharmacol) - "The disposition of PEGylated SN-38 is independent of UGT1A activity in rats, and PLX038 may find utility in full-dose treatment of patients who are UGT1A1*28 homozygotes or have metastatic disease with coincidental or incidental liver dysfunction."

Journal

[VIRTUAL] HIF2ALPHA PARTAKES TO AML DIFFERENTIATION BLOCKADE, AND ITS INHIBITION DRIVES AML DIFFERENTIATION (EHA 2020) - "When leukemia burden reached 5% in peripheral blood, mice were injected with 2mg/Kg EZN-2208 every other day for 5 days. Pro-differentiation activity of the specific HIF2α antagonist PT2385 was evaluated in AML cell lines, and ex vivo in AML cells from the bone marrow of 8 PDX models...Conclusion With this study, we defined a new role of HIF2α in the pathogenesis of AML, as a novel regulator of the AML differentiation blockade. Moreover, we suggest that HIF2α inhibition could be exploited as a new therapeutic avenue to treat AML, and to overcome resistance towards ATRA-induced differentiation therapy."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Ophthalmology

Randomized phase 2 study of pegylated SN-38 (EZN-2208) or irinotecan plus cetuximab in patients with advanced colorectal cancer (Cancer Sci) - P2, N=NA; PMID: 24105075; "The overall response rate and progression-free survival were 0% and 1.8 months, respectively, in arm A; 10.7% and 4.9 months (95% confidence interval [CI], 3.2-5.8 months), respectively, in arm B; and 14.3% and 3.7 months (95% CI, 2.1-5.8 months)."

P2 data • Biosimilar • Colorectal Cancer • Oncology