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NCT06690775PHASE2Recruiting

CATALINA-2: A Clinical Study of TORL-1-23 in Platinum-resistant Ovarian Cancer.

TORL Biotherapeutics, LLC

Start Date

11/20/2024

Completion Date

12/1/2027

Summary

A Phase 2 study to evaluate the safety and efficacy of TORL-1-23 in patients with advanced ovarian cancer.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: Participants are eligible to be included in the study only if all the following criteria apply: 1. Females ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the informed consent. 2. Participants must sign the informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 3. Disease Type: * Histologically or cytologically confirmed diagnosis of advanced (unresectable) or metastatic high grade serous ovarian, primary peritoneal (i.e, of primary origin), or fallopian tube cancer. High-grade endometrioid ovarian cancer is permitted for enrollment. * Participant's tumor must be positive for CLDN6 expression as defined by the CLDN6 reference laboratory assay. Tumor tissue will be required for submission for CLDN6 testing prior to Cycle 1 Day 1. * Participants must have platinum-resistant disease, defined as the following: * If participants received only 1 line of platinum-based therapy, they must have completed 4 or more cycles of platinum-containing therapy, must have achieved a CR or PR, and progressed \>3 months but ≤6 months after the last dose of platinum. * Participants who have received more than 1 line of platinum- based therapy must have progressed on or within 6 months after the last dose of platinum. * NOTE: This should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression (per RECIST v1.1). * Participants who are platinum-refractory during front-line treatment are excluded. * Participants must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, and for whom single- agent therapy is appropriate as the next line of treatment. Study rules for evaluation of number of prior systemic lines of therapy: * Adjuvant ± neoadjuvant is considered one line of therapy * Maintenance therapy (eg, bevacizumab or PARP inhibitors) will be considered part of the preceding line of therapy (ie, not counted independently) * Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently) * Hormonal therapy will not be counted as a separate line of therapy 4. Measurable disease, per RECIST v1.1 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. 6. Adequate organ function, based on the following laboratory values: * ANC: ≥1,500/mcL * Platelets: ≥100,000/mcL without transfusion within 4 weeks of first dose * Hemoglobin: 9 g/dL with transfusion or EPO support up to 14 days before eligibility assessment * Measured or calculated creatinine clearance with a validated formula\*: ≥30 mL/min * Serum total bilirubin: ≤1.5 X ULN (participants with known Gilbert disease or liver metastases who have serum bilirubin level ≤3×ULN may be enrolled * AST (SGOT) and ALT (SGPT): ≤3 X ULN (participants with active liver metastases who have ALT/AST ≤5 X ULN may be enrolled) * Albumin: ≥2.5 g/dL * ECG: 12-Lead ECG with normal tracing or non-clinically significant changes that do not require medical intervention and QTcF interval * 470 msec and without history of Torsades des Pointes or other symptomatic QTc abnormality. 7. Participants of childbearing potential must have a negative serum pregnancy test within 72 hours before starting study drug treatment. The serum pregnancy test must be negative for the participant to be eligible. 8. Participants must agree to use a highly effective birth control method from the time of the first study drug treatment through 7 months after the last study drug treatment, or be of nonchildbearing potential. 9. Participants must agree not to donate eggs from the first study drug treatment through 7 months after the last study drug treatment. 10. Participants must agree to not breastfeed from the first dose of study treatment through 90 days after the last dose of study treatment. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: 1. Has not recovered \[recovery is defined as National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0, Grade ≤1\] from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements. 2. Participants with clear cell, mucinous, sarcomatous (including carcinosarcoma), mixed histology, or low-grade, borderline ovarian tumors or non-epithelial ovarian cancers. 3. Participants with primary platinum-refractory ovarian, primary peritoneal (i.e. of primary origin) or fallopian tube cancer, defined as disease that did not respond to or has progressed within 3 months of the last dose of first line platinum-containing chemotherapy. 4. Received prior chemotherapeutic, investigational, radiotherapy, or other therapies for the treatment of cancer within 14 days with small molecule and within 28 days with biologic before the first dose of TORL-1-23. There is no waiting period required for stereotactic radiosurgery. 5. Prior treatment with a CLDN6-targeting agent or an MMAE-containing ADC. 6. Progressive or symptomatic brain metastases. Brain metastases that have been radiated, are asymptomatic, and on a stable or decreasing dose of steroids are allowed. Leptomeningeal disease is excluded. 7. Grade 2 or greater peripheral neuropathy. 8. History of non-infectious pneumonitis/ILD within 6 months of first dose of study drug. 9. Participants must not be considered a high medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. 10. History of significant cardiac disease: 1. Congestive heart failure \>New York Heart Association class 2 within last year 2. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) 3. Myocardial infarction less than 6 months before start of study drug 4. Anti-arrhythmic therapy (beta blockers are permitted) 5. Any unstable ischemic disease or untreated arrhythmia 11. Known history of myelodysplastic syndrome or acute myeloid leukemia. 12. History of another cancer within 3 years before Day 1 of study treatment, with the exception of basal or squamous cell carcinoma of the skin that has been definitively treated. Participants with malignancies with a low risk of recurrence, including appropriately treated ductal carcinoma in situ of the breast are not excluded. 13. Uncontrolled infection; active, clinically serious infections (CTCAE Grade \>2). 14. Participants with seizure disorder requiring medication. 15. Known hypersensitivity or intolerance to any of the study drugs, study drug classes, or excipients in the formulation. 16. History of having an allogeneic bone marrow or organ transplant. 17. Any condition (concurrent disease, infection, or comorbidity) that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator. 18. Participants who are taking any drugs that are strong inducers and/or strong inhibitors of CYP3A4 enzymes. 19. Participants who are taking any drugs that are inhibitors of P-glycoprotein.

Interventions

DRUG

TORL-1-23

DRUG

TORL-1-23

DRUG

TORL-1-23

DRUG

Pegfilgrastim (drug)

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Conditions

Epithelial Ovarian CancerPrimary PeritonealFallopian Tube CancerEndometrioid Ovarian Cancer

Locations

Mayo Clinic Hospital

Phoenix, Arizona 85054

United States

SCRI - Arizona Oncology Associates, PC-HOPE

Tucson, Arizona 85711

United States

City of Hope National Medical Center

Duarte, California 91010

United States

Providence St. Jude Medical Center

Fullerton, California 92835

United States

UCLA - JCCC Clinical Research Unit

Los Angeles, California 90095

United States

Stanford Cancer Center

Palo Alto, California 94304

United States

SCRI - Sansum Clinic

Santa Barbara, California 93105

United States

Smilow Cancer Hospital at Yale - New Haven

New Haven, Connecticut 06510

United States

Mayo Clinic Florida

Jacksonville, Florida 32224

United States

Winship Cancer Institute, Emory University

Atlanta, Georgia 30322

United States

University of Chicago Medical Center

Chicago, Illinois 60637

United States

SCRI - Maryland Oncology Hematology, P.A.

Annapolis, Maryland 21401

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

SCRI - Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota 55404

United States

University of Minnesota

Minneapolis, Minnesota 55404

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Washington University

St Louis, Missouri 63108

United States

Rutgers Cancer Institute

New Brunswick, New Jersey 08901

United States

Duke Cancer Center

Durham, North Carolina 27710

United States

The James Cancer Hospital and Solove Research Institute - Ohio State University

Columbus, Ohio 43210

United States

Stephenson Cancer Center at the University of Oklahoma

Oklahoma City, Oklahoma 73104

United States

SCRI - Northwest Cancer Specialists, P.C.

Portland, Oregon 97227

United States

SCRI - Alliance Cancer Specialists, PC

Doylestown, Pennsylvania 18901

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19104-4238

United States

SCRI - Texas Oncology

Fort Worth, Texas 76104

United States

SCRI - Virginia Oncology Associates

Norfolk, Virginia 23502

United States

Monash Medical Centre

Clayton, Melbourne VIC 3168

Australia

Blacktown Hospital

Blacktown, New South Wales 2148

Australia

Icon Cancer Centre Chermside

Chermside, Queensland QLD 4032

Australia

Flinders Medical Centre

Bedford Park, South Australia 5042

Australia

Linear Clinical Research

Perth, Western Australia WA 6009

Australia

Medizinische Universitat Landeskrankenhaus Graz

Graz, Styria 8036

Austria

Universitatsklinik Innsbruck

Innsbruck, Tyrol 6020

Austria

Ordensklinikum Linz

Linz, Upper Austria 4010

Austria

Antwerp University Hospital (UZA)

Edegem, Antwerp 2650

Belgium

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, Brussels Capital 1200

Belgium

UZ Leuven

Leuven, Flemish Brabant 3000

Belgium

CHU Liège

Liège, Wallonia B-4000

Belgium

BC Cancer - Abbotsford

Abbotsford British Columbia, British Columbia V2S 0C2

Canada

British Columbia Cancer Agency (BC Cancer, part of the Provincial Health Services Authority)

Vancouver, British Columbia V5Z 4E6

Canada

Sunnybrook Research Institute

Toronto, Ontario M4N 3M5

Canada

Princess Margaret Cancer Centre - University Health Network (UHN)

Toronto, Ontario M5G 2M9

Canada

Hospital Maisonneuve Rosemont

Montreal, Quebec H1T 2M4

Canada

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec H2X 0C2

Canada

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec H3T 1E2

Canada

McGill University Health Centre (MUHC) - Royal Victoria Hospital

Montreal, Quebec H4A 3J1

Canada

Centre Leon Berard

Lyon, Auvergne- Rhôn-Alpes 69008

France

Institut de Cancérologie de l'Ouest

Saint-Herblain, Pays de la Loire Region 44805

France

Institut Gustave Roussy

Villejuif, Île-de-France Region 94805

France

Universitatsklinikum Heidelberg

Heidelberg, Baden-Wurttenberg 69120

Germany

Universitätsklinikum Erlangen

Erlangen, Bavaria 91054

Germany

Charité Universitätsmedizin Berlin

Berlin, State of Berlin 13353

Germany

Start Dublin - Mater Misericordiae University Hospital

Dublin, Leinster D07 R2WY

Ireland

St. James Hospital

Dublin, Leinster DO8C9X2

Ireland

IRCCS Giovani Paolo II - Instituto Oncologico

Bari, Apulia 70124

Italy

Humanitas San Pio X

Milan, Milano 20159

Italy

Nuovo Ospedale di Prato S Stefano

Prato, Prato 59100

Italy

Fondazione Policlinico Universitario A. Gemelli IRCCS

Rome, Rome 00168

Italy

National University Cancer Institute

Singapore, Singapore 119074

Singapore

National Cancer Centre

Singapore, Singapore 168583

Singapore

Curie Oncology (Farrer)

Singapore, Singapore 217562

Singapore

Seoul National University Hospital

Seoul, Gwanak-gu 03080

South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, Seocho-Gu 06591

South Korea

Yonsei University Health System, Severance Hospital

Seoul, Seodaemun-Gu 03722

South Korea

Asan Medical Center

Seoul, Songpa-Gu 05505

South Korea

Institut Catalá d'Oncologia de Girona

Girona, Catalonia 17007

Spain