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

Phase 2

Recruiting

• Conditions: Ovarian Cancer; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; Platinum-resistant Ovarian Cancer
• Interventions: Drug: Gemcitabine; Drug: Luveltamab tazevibulin; Drug: Pegfilgrastim; Drug: Paclitaxel; Drug: Pegylated liposomal doxorubicin; Drug: Topotecan

• 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.

Study Timeline

• Study First Submitted: 2023-05-12
• Study First Submitted QC: 2023-05-12
• Study First Posted: 2023-05-23
• Study Start: 2023-07-12
• Status Verified: 2024-04
• Last Update Submitted: 2024-08-27
• Last Update Posted: 2024-08-29
• Primary Completion: 2027-08
• Study Completion: 2028-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 600

Inclusion Criteria

1. High grade serous epithelial ovarian cancer, fallopian tube or primary peritoneal cancer
2. Age ≥ 18 years
3. ECOG performance status 0 to 1
4. Positive FOLR1 expression per central laboratory testing
5. Relapsed platinum-resistant epithelial ovarian cancer and received a total of 1 to 3 prior regimens
6. Prior bevacizumab treatment is required, if labeled and available as standard of care per institutional guidelines, unless subject has documented contraindication
7. At least 1 measurable target lesion per RECIST v1.1
8. Adequate organ function

Exclusion Criteria

1. Low grade (Grade 1) ovarian carcinoma, clear cell, mucinous, endometrioid, sarcomatous, and mixed histology ovarian carcinomas
2. Prior treatment with a FOLR1- targeting ADCs or with ADCs that contain a tubulin inhibitor
3. Primary platinum-refractory disease
4. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to antibody-related fusion protein treatment
5. 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
6. Previous solid organ transplantation
7. History or clinical signs of meningeal or active central nervous system involvement
8. 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)

Arizona Oncology Associates, PC-Hope; 🇺🇸 Tucson, Arizona, United States

Sutter Health; 🇺🇸 Daly City, California, United States

MedStar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

Baptist Health South Florida (BHSF) - Miami Cancer Institute; 🇺🇸 Miami, Florida, United States

USF Research & Innovation; 🇺🇸 Tampa, Florida, United States

Sinai Hospital of Baltimore; 🇺🇸 Baltimore, Maryland, United States

University of Massachusetts Chan Medical School; 🇺🇸 Worcester, Massachusetts, United States

Minnesota Oncology Hematology; 🇺🇸 Minneapolis, Minnesota, United States

Nebraska Methodist Hospital; 🇺🇸 Omaha, Nebraska, United States

Optimum Clinical Research Group; 🇺🇸 Albuquerque, New Mexico, United States

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