REFRaME-O1: A Study to Investigate the Efficacy and Safety of Luveltamab Tazevibulin Versus Investigator's Choice (IC) Chemotherapy in Women With Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) Expressing FOLR1
- Conditions
- Ovarian CancerEpithelial Ovarian CancerFallopian Tube CancerPrimary Peritoneal CancerPlatinum-resistant Ovarian Cancer
- Interventions
- Registration Number
- NCT05870748
- Lead Sponsor
- Sutro Biopharma, Inc.
- Brief Summary
A Phase 2/3 study to investigate the efficacy and safety of luveltamab tazevibulin versus IC chemotherapy in women with ovarian cancer (including fallopian tube or primary peritoneal cancers) expressing FOLR1.
- Detailed Description
This is a randomized, multicenter, international, open-label, 2-part, Phase 2/3 study designed to assess the efficacy and safety of luveltamab tazevibulin versus IC chemotherapy in subjects with relapsed platinum-resistant epithelial ovarian cancer expressing FOLR1.
Part 1 will consist of 2 luveltamab tazevibulin dosing cohorts (Cohort A and Cohort B), with subjects randomized 1:1. Part 1 will be used to select the optimized dosing regimen.
Part 2 will further evaluate the efficacy and safety of the selected dosing regimen versus IC chemotherapy.
Luveltamab tazevibulin will be administered intravenously (IV) over a 1-hour infusion time every 3 weeks.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 600
- High grade serous epithelial ovarian cancer, fallopian tube or primary peritoneal cancer
- Age ≥ 18 years
- ECOG performance status 0 to 1
- Positive FOLR1 expression per central laboratory testing
- Relapsed platinum-resistant epithelial ovarian cancer and received a total of 1 to 3 prior regimens
- Prior bevacizumab treatment is required, if labeled and available as standard of care per institutional guidelines, unless subject has documented contraindication
- At least 1 measurable target lesion per RECIST v1.1
- Adequate organ function
- Low grade (Grade 1) ovarian carcinoma, clear cell, mucinous, endometrioid, sarcomatous, and mixed histology ovarian carcinomas
- Prior treatment with a FOLR1- targeting ADCs or with ADCs that contain a tubulin inhibitor
- Primary platinum-refractory disease
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to antibody-related fusion protein treatment
- Pre-existing clinically significant ocular disorders, severe chronic obstructive pulmonary disease or asthma, clinically significant cardiac or cerebrovascular disease, or other significant concurrent, uncontrolled medical condition
- Previous solid organ transplantation
- History or clinical signs of meningeal or active central nervous system involvement
- Concurrent participation in another therapeutic treatment trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Luveltamab tazevibulin dose Cohort A Pegfilgrastim 5.2 mg/kg q3w with prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg q3w for Cycle 3 onwards Part 2: IC Chemotherapy Pegylated liposomal doxorubicin * Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 q4w or 1000mg/m2 on Days 1 and 8 q3w * Paclitaxel 80 mg/m2 on Days 1, 8, and 15 q4w * Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 q4w * Topotecan 4.0 mg/m2on Day 1, 8, and 15 q4w or 1.25 mg/m2 on Days 1 - 5 q3w Part 2: IC Chemotherapy Gemcitabine * Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 q4w or 1000mg/m2 on Days 1 and 8 q3w * Paclitaxel 80 mg/m2 on Days 1, 8, and 15 q4w * Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 q4w * Topotecan 4.0 mg/m2on Day 1, 8, and 15 q4w or 1.25 mg/m2 on Days 1 - 5 q3w Part 2: IC Chemotherapy Paclitaxel * Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 q4w or 1000mg/m2 on Days 1 and 8 q3w * Paclitaxel 80 mg/m2 on Days 1, 8, and 15 q4w * Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 q4w * Topotecan 4.0 mg/m2on Day 1, 8, and 15 q4w or 1.25 mg/m2 on Days 1 - 5 q3w Part 2: IC Chemotherapy Topotecan * Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 q4w or 1000mg/m2 on Days 1 and 8 q3w * Paclitaxel 80 mg/m2 on Days 1, 8, and 15 q4w * Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 q4w * Topotecan 4.0 mg/m2on Day 1, 8, and 15 q4w or 1.25 mg/m2 on Days 1 - 5 q3w Luveltamab tazevibulin dose Cohort A Luveltamab tazevibulin 5.2 mg/kg q3w with prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg q3w for Cycle 3 onwards Luveltamab tazevibulin dose Cohort B Luveltamab tazevibulin 4.3 mg/kg q3w
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) up to 24 months Best response of complete response (CR) or partial response (PR) per RECIST 1.1.
Progression Free Survival (PFS) up to 24 months time between the date of first dose and the first date of documented progression or death
- Secondary Outcome Measures
Name Time Method Incidence and severity of adverse events [Safety and tolerability] up to 24 months Incidence and severity of adverse events (AEs) and clinical laboratory abnormalities.
Quality of life (QLQ-OV28) up to 24 months Quality of Life Questionnaire Ovarian Cancer 28 is a 28-item ovarian cancer supplemental module that evaluates the quality of life of ovarian cancer patients. It assesses abdominal/gastrointestinal symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal/menopausal symptoms, body image, attitude to disease/treatment and sexual functioning.
Overall Survival (OS) up to 24 months Time between date of first dose and date of death due to an cause or end of study.
Duration of Response (DOR) up to 24 months Confirmed CR or PR from the first documented response to the date of documented disease progression or death.
Trial Locations
- Locations (39)
Texas Oncology
🇺🇸Dallas, Texas, United States
Ohio State University Center
🇺🇸Columbus, Ohio, United States
Baptist Health South Florida (BHSF) - Miami Cancer Institute
🇺🇸Miami, Florida, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Texas Oncology-San Antonio
🇺🇸San Antonio, Texas, United States
NYU Langone Health
🇺🇸New York, New York, United States
Minnesota Oncology Hematology
🇺🇸Minneapolis, Minnesota, United States
Arizona Oncology Associates, PC-Hope
🇺🇸Tucson, Arizona, United States
Yonsei University, Severance Hospital
🇰🇷Seoul, Korea, Republic of
Princess Margaret Cancer Center
🇨🇦Toronto, Canada
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Curie Centre, Oncology centre
🇸🇬Novena, Singapore
Health New Zealand - Te Whatu Ora Capital, Coast, and Hutt Valley - Wellington Regional Hospital
🇳🇿Newtown, Wellington, New Zealand
McGill University Health Centere (MUHC)-Glen Site
🇨🇦Montréal, Quebec, Canada
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Gachon University Gil Hospital
🇰🇷Incheon, Korea, Republic of
Providence Gynecologic Oncology Clinic
🇺🇸Portland, Oregon, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
USF Research & Innovation
🇺🇸Tampa, Florida, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Sutter Health
🇺🇸Daly City, California, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
University of Massachusetts Chan Medical School
🇺🇸Worcester, Massachusetts, United States
Good Samaritan Hospital Medical Center
🇺🇸West Islip, New York, United States
Oncology Associates of Oregon, PC
🇺🇸Eugene, Oregon, United States
Kettering Health
🇺🇸Kettering, Ohio, United States
Oklahoma Cancer Specialists and Research Institute- Tulsa Cancer Center
🇺🇸Tulsa, Oklahoma, United States
Lancaster General Hospital
🇺🇸Lancaster, Pennsylvania, United States
Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Texas Oncology-DFW
🇺🇸Dallas, Texas, United States
Texas Oncology - The Woodlands
🇺🇸The Woodlands, Texas, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Sheba Medical Center
🇮🇱Ramat Gan, Israel
National Cancer Center
🇰🇷Gyeonggi-do, Korea, Republic of
National Cancer Center Singapore
🇸🇬Singapore, Singapore
Optimum Clinical Research Group
🇺🇸Albuquerque, New Mexico, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia