PLX038 / ProLynx - LARVOL DELTA

THERAPEUTIC POTENTIAL OF SN-38 AND ITS PEGYLATED FORM PLX038 IN A NEWLY ESTABLISHED PRECLINICAL COHORT OF EMBRYONAL TUMORS WITH MULTILAYERED ROSETTES. (SIOP 2025) - "Chemotherapeutics, including topoisomerase II inhibitor SN-38 (the active metabolite of irinotecan) and vincristine, as well as targeted drugs, including FGFR inhibitors (futibatinib) and XPO1 inhibitors (selinexor), were identified as potential candidate drugs for ETMR. Conclusions Altogether, these new preclinical ETMR models will accelerate the development of novel therapies and clinical trials. Furthermore, irinotecan derivatives SN-38 and PLX038 emerged as strong therapeutic candidates for ETMR."

Preclinical • Brain Cancer • Embryonal Tumor • Oncology • Pediatrics • Solid Tumor

TOPOLOGY: A Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Institut Curie | Trial completion date: Mar 2026 ➔ Apr 2027 | Trial primary completion date: Aug 2025 ➔ Apr 2027

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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

POP-ART: A Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=92 | Recruiting | Sponsor: Institut Curie | Trial primary completion date: Sep 2027 ➔ Sep 2028

Trial primary completion date • Oncology • Solid Tumor

POP-ART: A Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=92 | Recruiting | Sponsor: Institut Curie | Not yet recruiting ➔ Recruiting | Trial completion date: Feb 2029 ➔ Sep 2029 | Initiation date: Jun 2024 ➔ Jan 2025 | Trial primary completion date: Jun 2025 ➔ Sep 2027

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Oncology • 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

Phase II clinical trial of PLX038 in patients with platinum resistant ovarian, primary peritoneal and fallopian tube cancer. (ASCO 2024) - P2 | "Irinotecan also has a 15-25% response rate in some studies of platinum-resistant epithelial ovarian cancer but does not have FDA approval for this indication. All patients must have an ECOG performance status of 0, 1, or 2 and adequate bone marrow, renal, and hepatic function. As of January 31, 2024, 12 of planned 37 patients have enrolled."

Clinical • P2 data • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • CTCs • SLFN11 • 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

TOPOLOGY: A Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Institut Curie | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Breast Cancer • Febrile Neutropenia • Oncology • Solid Tumor • Triple Negative Breast Cancer

POP-ART: A Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=92 | Not yet recruiting | Sponsor: Institut Curie

Combination therapy • Metastases • New P1 trial • Oncology • Solid Tumor

ProLynx announces initiation of the Phase II Topology clinical trial of its DNA-damaging agent PLX038 in triple-negative breast cancer at the Institut Curie (GlobeNewswire) - "ProLynx Inc. announced that the first patient was included in TOPOLOGY by investigator Dr. Delphine Loirat, with a Phase II clinical trial investigating PLX038 (PEG~SN-38) for locally-advanced or metastatic triple-negative breast cancer (TNBC). Patients will have been previously treated with at least two therapies, including the antibody-drug conjugate (ADC) sacituzumab govitecan (SG; Trodelvy)."

Trial status • Oncology • Solid Tumor • Triple Negative Breast Cancer

ProLynx announces initiation of Phase I/II clinical trial of its DNA-damaging agent PLX038 in patients with rare CNS tumors at the National Cancer Institute (NCI) (GlobeNewswire) - "ProLynx Inc. announced today that the first patient was treated with PLX038 (PEGylated SN-38) in a Phase I/II clinical trial for primary CNS tumors driven by MYC or MYCN amplifications. National Institutes of Health’s NCI investigators Dr. Marta Penas-Prado and Dr. Mark Gilbert are conducting the trial...The NCI trial will assess whether PLX038 is safe and efficacious in primary CNS tumors driven by MYC or MYCN amplifications. The Phase I trial will confirm the recommended Phase II dose...Notably, the Phase II trial will incorporate on-treatment tumor biopsies to investigate biomarkers of response and resistance, including SLFN11, MYC, MYCN and Top1, 2a, and 2b expression."

Trial status • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Glioma • Medulloblastoma • Oncology • Solid Tumor

ProLynx announces a publication proposing that a long-acting prodrug of SN-38 could be effective in treating Sacituzumab Govitecan-Resistant Tumors (GlobeNewswire) - "ProLynx Inc...announced publication of a paper...in BioDrugs...The authors of the publication argue that sacituzumab govitecan is not a conventional ADC since it spontaneously releases a high level of the SN-38 in the systemic circulation; the released SN-38 is so high in concentration that it must have activity apart from its action as an ADC payload. Hence, sacituzumab govitecan likely acts as a simple prodrug of systemic SN-38 as well as an ADC. The authors posit that a long-acting SN-38, such as ProLynx PLX038, should be an efficacious and less toxic prodrug of systemic SN-38 than sacituzumab govitecan, and could serve as a therapy for certain forms of resistance mechanisms to sacituzumab govitecan."

Clinical data • Oncology • Solid Tumor

Could a Long-Acting Prodrug of SN-38 be Efficacious in Sacituzumab Govitecan-Resistant Tumors? (PubMed, BioDrugs) - "We previously proposed that sacituzumab govitecan (SG, Trodelvy®) likely acts as a simple prodrug of systemic SN-38 as well as an antibody drug conjugate (ADC). Finally, we suggest possible mechanisms of SG resistance and how PLX038 might perform in the context of each. Taken together, we argue that-contrary to many opinions-SG does not exclusively act as a conventional ADC, and propose that PLX038 may be efficacious in some settings of SG-resistance."

Journal • Oncology

PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • CNS Tumor • Ependymoma • Glioma • Medulloblastoma • Oncology • Solid Tumor • MYCN

PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications (clinicaltrials.gov) - P1/2 | N=120 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1/2 trial • Brain Cancer • CNS Tumor • Ependymoma • Glioma • Medulloblastoma • Oncology • Solid Tumor • MYCN

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

TOPOLOGY: A Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - P2 | N=44 | Not yet recruiting | Sponsor: Institut Curie

New P2 trial • Breast Cancer • Febrile Neutropenia • Oncology • Solid Tumor • Triple Negative Breast Cancer

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

A Phase I Study of PLX038 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: ProLynx LLC | Unknown status ➔ Completed | N=72 ➔ 40 | Trial completion date: Jun 2020 ➔ Jul 2023 | Trial primary completion date: Dec 2019 ➔ Feb 2023

Enrollment change • Metastases • Trial completion • Trial completion date • Trial primary completion date • 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