Phase 2 Evaluation of TORL-1-23 Monotherapy in Advanced Platinum-Resistant Epithelial Ovarian, Primary Peritoneal, and Fallopian Tube Cancers Expressing Claudin 6

The primary objective of the CATALINA-2 Phase 2 study is to evaluate the **efficacy** of TORL-1-23 as a monotherapy in women with advanced platinum-resistant **ovarian cancer** expressing Claudin 6 (CLDN6). This is clinically relevant as platinum-resistant ovarian cancer presents a significant treatment challenge, and identifying effective therapies could improve patient outcomes. The study focuses on women with advanced stages of ovarian, fallopian tube, and peritoneal cancers, which are known for their poor prognosis and limited treatment options. The trial aims to provide insights into the potential of TORL-1-23, a humanized IgG1 monoclonal antibody conjugated to monomethyl auristatin E, in targeting CLDN6, a protein expressed in these cancer types.

The clinical trial involves a total of **71 participants**, all of whom are **female** and aged **18 years or older**. The study population consists of individuals with a confirmed diagnosis of advanced or metastatic high-grade serous **ovarian cancer**, primary peritoneal cancer, or fallopian tube cancer that is resistant to platinum-containing therapy. Participants were selected based on the expression of claudin 6 in their tumors, as determined by a specific laboratory assay. The trial does not include male subjects or vulnerable populations. Participants are required to have measurable tumors at baseline. No specific lifestyle considerations such as diet or physical activity are mentioned for this study.

The clinical trial is designed to evaluate the efficacy and safety of **TORL-1-23**, a **humanised IgG1 monoclonal antibody** against **CLDN6**, in women with advanced platinum-resistant epithelial ovarian cancer, including primary peritoneal and fallopian tube cancers. This is a Phase II, randomized, double-blind, controlled study. The trial is expected to commence recruitment on July 15, 2025, and conclude by July 15, 2028, with an estimated duration of 24 months for each participant. The study will involve multiple visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and tumor expression of **claudin 6**. Participants will undergo regular follow-up visits to monitor treatment response and safety, with the primary endpoint being the Objective Response Rate (ORR) per RECIST version 1.1, assessed by a blinded independent central review. The end-of-study visit will evaluate the overall treatment outcomes and any adverse events. Participants are expected to remain in the study for the full duration unless they experience significant adverse effects, disease progression, or choose to withdraw consent. The trial will utilize **TORL-1-23** administered as a **lyophilized powder for solution for injection** via **intravenous infusion**, with a maximum daily dose of 3.4 mg/kg and a total dose not exceeding 119 mg over the treatment period. Conditions for early termination include non-compliance with the protocol, withdrawal of consent, or any medical condition that contraindicates continued participation. The study aims to provide valuable insights into the potential benefits of **TORL-1-23** as a monotherapy for this patient population.

The clinical trial involves the administration of **TORL-1-23**, an experimental medication formulated as a **lyophilized powder for solution for injection**. This investigational product is a **humanised IgG1 monoclonal antibody** targeting **Claudin 6 (CLDN6)**, conjugated to **monomethyl auristatin E** via a **cathepsin hydrolysable dipeptide VC linker**. The medication is administered through **intravenous infusion**. The dosing regimen specifies a maximum daily dose of **3.4 mg/kg** and a total maximum dose of **119 mg/kg** over a treatment period of up to **24 weeks**. Participant compliance with the dosing schedule will be monitored throughout the study.

In addition to the experimental treatment, the study includes the use of **PEGFILGRASTIM**, a non-experimental auxiliary treatment. PEGFILGRASTIM is a **granulocyte-colony-stimulating factor (G-CSF)**, administered as an **injection**. The pharmaceutical form is denoted as **PHF00231MIG**. The maximum daily dose for PEGFILGRASTIM is **6 mg**, with a total maximum dose of **210 mg** over the same **24-week** treatment period. This auxiliary treatment is intended to support the participants' immune system during the trial. Compliance with the administration of PEGFILGRASTIM will also be monitored to ensure adherence to the study protocol.

The efficacy of the investigational product, TORL-1-23, in the clinical trial will be assessed primarily through the **Objective Response Rate (ORR)**. This endpoint will be evaluated according to the RECIST version 1.1 criteria, which involves determining the confirmed best overall response of partial or complete responses. The assessment will be conducted by a blinded independent central review (BICR) to ensure objectivity and accuracy in the evaluation of tumor response. The trial is designed to evaluate the efficacy of TORL-1-23 as a monotherapy in women with advanced platinum-resistant ovarian cancer expressing Claudin 6 (CLDN6).