Epithelial Ovarian Cancer, Fallopian Tube Cancer, Ovarian Cancer, Platinum-resistant Ovarian Cancer, Primary Peritoneal Cancer
Conditions
Keywords
FOLR1, FolRα, FRα, folate receptor alpha, antibody drug conjugate, Luveltamab tazevibulin, STRO-002, luvelta
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.
Interventions
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.
DRUGPegfilgrastim
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.
DRUGGemcitabine
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.
DRUGPaclitaxel
Paclitaxel is a chemotherapy regimen approved for treatment of previously treated ovarian cancer. It stabilizes microtubules, inhibiting tumor cell replication.
DRUGPegylated 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.
DRUGTopotecan
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.
Sponsors
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Asia-Pacific Gynecologic Oncology Trials Group (APGOT)
GOG Foundation
Sutro Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | up to 24 months | time between the date of first dose and the first date of documented progression or death |
| Objective Response Rate (ORR) | up to 24 months | Best response of complete response (CR) or partial response (PR) per RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Australia, Canada, Israel, New Zealand, Singapore, South Korea, United States
Outcome results
None listed