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

Ovarian Cancer Clinical Trial

Official title:

REFRaME-O1: A Phase 2/3 Open-label Study Evaluating the Efficacy and Safety of Luveltamab Tazevibulin (STRO-002) Versus Investigator's Choice (IC) Chemotherapy in Women With Relapsed Platinum-resistant Epithelial Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) Expressing Folate Receptor Alpha (FOLR1)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05870748
• Other study ID #: STRO-002-GM3
• Secondary ID: GOG-3086ENGOT-OV
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 12, 2023
• Est. completion date: February 2026

Study information

• Verified date: April 2024
• Source: Sutro Biopharma, Inc.
• Contact: Craig Berman, MD
• Phone: 650-801-6417
• Email: STRO-002ClinDev[@]sutrobio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: February 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Epithelial Ovarian Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Neoplasms
• Platinum-resistant Ovarian Cancer
• Primary Peritoneal Cancer

Intervention

Drug:
• Luveltamab tazevibulin
Luveltamab tazevibulin is an antibody-drug conjugate targeting FOLR1. It consists of an IgG1 antibody (SP8166) conjugated to cleavable 3-3-aminophenyl hemiasterlin drug-linkers at 4 sites. The active warhead (SC209) inhibits tubulin polymerization leading to mitotic arrest and cell death.
• Pegfilgrastim
Pegfilgrastim or pegylated G-CSF is approved and used to decrease the incidence of infection in patients receiving myelosuppressive anti-cancer drugs. It increases the proliferation and differentiation of neutrophils.
• Gemcitabine
Gemcitabine is a chemotherapy regimen used for treating platinum-resistant ovarian cancer. It inhibits ribonucleotide reductase and DNA polymerase, hindering tumor cell growth and promoting cell death.
• Paclitaxel
Paclitaxel is a chemotherapy regimen approved for treatment of previously treated ovarian cancer. It stabilizes microtubules, inhibiting tumor cell replication.
• Pegylated liposomal doxorubicin
Pegylated liposomal doxorubicin is a chemotherapy regimen approved for treating platinum-resistant ovarian cancer. It inhibits DNA and RNA synthesis by intercalating between base pairs, obstructing tumor cell division.
• Topotecan
Topotecan is a chemotherapy regimen approved for treatment of metastatic ovarian cancer after disease progression on or after initial or subsequent chemotherapy. It binds to topoisomerase I inducing DNA breaks and subsequent tumor cell apoptosis.

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Canada	McGill University Health Centere (MUHC)-Glen Site	Montréal	Quebec
Canada	Princess Margaret Cancer Center	Toronto
Israel	Sheba Medical Center	Ramat Gan
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Gachon University Gil Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Yonsei University, Severance Hospital	Seoul
Singapore	Curie Centre, Oncology centre	Novena
Singapore	National Cancer Center Singapore	Singapore
United States	Optimum Clinical Research Group	Albuquerque	New Mexico
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Ohio State University Center	Columbus	Ohio
United States	Texas Oncology	Dallas	Texas
United States	Texas Oncology-DFW	Dallas	Texas
United States	Sutter Health	Daly City	California
United States	Oncology Associates of Oregon, PC	Eugene	Oregon
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Kettering Health	Kettering	Ohio
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Baptist Health South Florida (BHSF) - Miami Cancer Institute	Miami	Florida
United States	Minnesota Oncology Hematology	Minneapolis	Minnesota
United States	NYU Langone Health	New York	New York
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Providence Gynecologic Oncology Clinic	Portland	Oregon
United States	Texas Oncology-San Antonio	San Antonio	Texas
United States	USF Research & Innovation	Tampa	Florida
United States	Texas Oncology - The Woodlands	The Woodlands	Texas
United States	Arizona Oncology Associates, PC-Hope	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute- Tulsa Cancer Center	Tulsa	Oklahoma
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Good Samaritan Hospital Medical Center	West Islip	New York
United States	University of Massachusetts Chan Medical School	Worcester	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Sutro Biopharma, Inc.	Asia-Pacific Gynecologic Oncology Trials Group (APGOT), European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Israel,  Korea, Republic of,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	time between the date of first dose and the first date of documented progression or death	up to 24 months
Primary	Objective Response Rate (ORR)	Best response of complete response (CR) or partial response (PR) per RECIST 1.1.	up to 24 months
Secondary	Overall Survival (OS)	Time between date of first dose and date of death due to an cause or end of study.	up to 24 months
Secondary	Duration of Response (DOR)	Confirmed CR or PR from the first documented response to the date of documented disease progression or death.	up to 24 months
Secondary	Incidence and severity of adverse events [Safety and tolerability]	Incidence and severity of adverse events (AEs) and clinical laboratory abnormalities.	up to 24 months
Secondary	Quality of life (QLQ-OV28)		up to 24 months