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

Sutro Biopharma

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Primary Peritoneal Cancer; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Ovarian Cancer; Platinum-resistant Ovarian Cancer

Treatments: Drug: Luveltamab tazevibulin; Drug: Gemcitabine; Drug: Pegfilgrastim; Drug: Topotecan; Drug: Paclitaxel; Drug: Pegylated liposomal doxorubicin

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT05870748

GEICO-134-O (Other Identifier)

STRO-002-GM3

GOG-3086 (Other Identifier)

ENGOT-OV79 (Other Identifier)

APGOT-OV9 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 600 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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600 participants in 3 patient groups

Luveltamab tazevibulin dose Cohort A

Experimental group

Description:

5.2 mg/kg q3w with prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg q3w for Cycle 3 onwards

Treatment:

Drug: Pegfilgrastim

Drug: Luveltamab tazevibulin

Luveltamab tazevibulin dose Cohort B

Experimental group

Description:

4.3 mg/kg q3w

Treatment:

Drug: Luveltamab tazevibulin

Part 2: IC Chemotherapy

Active Comparator group

Description:

* 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

Treatment:

Drug: Pegylated liposomal doxorubicin

Drug: Paclitaxel

Drug: Topotecan

Drug: Gemcitabine