Efficacy and Safety Evaluation of Luveltamab Tazevibulin Versus Investigator's Choice Chemotherapy in Relapsed Platinum-Resistant Epithelial Ovarian Cancer Expressing FOLR1
- Trial ID
- 2024-512477-27-00
- Protocol
- STRO-002-GM3
- Sponsor
- Sutro Biopharma Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of luveltamab tazevibulin compared to investigator's choice (IC) chemotherapy in women with relapsed platinum-resistant advanced epithelial ovarian cancer, including fallopian tube or primary peritoneal cancers, expressing folate receptor alpha (FOLR1). This is clinically relevant as it aims to determine the potential of luveltamab tazevibulin as a more effective treatment option for this patient population, which is characterized by limited therapeutic alternatives and poor prognosis.
Secondary objectives include:
- To assess additional efficacy outcome measures of luveltamab tazevibulin versus IC chemotherapy.
- To evaluate the safety and tolerability of luveltamab tazevibulin compared to IC chemotherapy.
- To evaluate ovarian cancer-specific quality of life using the European Organisation for the Research and Treatment of Cancer (EORTC) ovarian cancer-specific quality of life questionnaire (QLQ OV28).
Participants
The clinical trial involves a total of **392 participants** diagnosed with **Advanced Epithelial Ovarian Cancer**, including fallopian tube or primary peritoneal cancers. The study population is exclusively female, with an age requirement of 18 years and older. Participants were selected based on specific inclusion criteria, including a confirmed diagnosis of high-grade serous epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer, and a positive FOLR1 expression. The trial excludes male subjects and does not involve a vulnerable population. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Lifestyle considerations such as diet and physical activity are not specified, but participants must have adequate bone marrow, liver, and renal function, and a life expectancy of more than three months. Prior treatment with bevacizumab is required unless contraindicated, and participants must be candidates for specific chemotherapy regimens for platinum-resistant disease. The trial does not include individuals who are pregnant or breastfeeding, and those of childbearing potential must adhere to strict contraceptive measures during and after the study.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **luveltamab tazevibulin** compared to investigator's choice chemotherapy in women with relapsed platinum-resistant **advanced epithelial ovarian cancer**, including fallopian tube or primary peritoneal cancers, expressing folate receptor alpha (FOLR1). This is a Phase 2/3 open-label study, employing a randomized, controlled trial design. The trial is expected to commence recruitment on May 31, 2024, and conclude by May 31, 2027, with an estimated duration of 36 months.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, performance status, and specific laboratory parameters. The screening will ensure that participants have high-grade serous epithelial ovarian cancer and meet other inclusion criteria, such as adequate bone marrow, liver, and renal function. Following the screening, eligible participants will be randomized to receive either the investigational drug or standard chemotherapy. Study visits will occur at regular intervals to monitor treatment efficacy and safety, including assessments of progression-free survival and objective response rate per RECIST 1.1 criteria.
Follow-up visits will be scheduled to evaluate secondary endpoints, such as overall survival, duration of response, and incidence of adverse events. The end-of-study visit will mark the completion of the participant's involvement, which is anticipated to last up to 24 months, depending on individual response and tolerability. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, or withdrawal of consent. Participants will be closely monitored throughout the trial to ensure adherence to the protocol and to address any safety concerns promptly.
Treatment
The clinical trial involves the administration of several **experimental medications** and comparator treatments. The primary experimental medication is **STRO-002**, also known as anti-FolRα-ADC, provided by Sutro Biopharma, Inc. This medication is formulated as a **solution for infusion** and is administered intravenously. The dosing regimen for STRO-002 is set at a maximum daily dose of 5.2 mg/kg, with a total maximum dose of 124.8 mg/kg over a treatment period of 24 weeks. The administration is monitored to ensure compliance with the dosing schedule.
One of the comparator treatments is **HYCAMTIN**, which contains the active substance **topotecan**. It is provided as a 4 mg powder for concentrate for solution for infusion by Sandoz Pharmaceuticals D.D. The pharmaceutical form is a **solution for infusion**, administered intravenously. The maximum daily dose is 4 mg/m², with a total maximum dose of 96 mg/m² over 24 weeks.
Another comparator is **TAXOL**, containing **paclitaxel** as the active substance. Manufactured by Cheplapharm Arzneimittel GmbH, it is available as a 6 mg/ml concentrate for solution for infusion. The administration route is intravenous infusion, with a maximum daily dose of 80 mg/m² and a total maximum dose of 1920 mg/m² over the treatment period.
**Neulasta**, containing **pegfilgrastim**, is used as an auxiliary treatment. Provided by Amgen Europe B.V., it is formulated as a 6 mg solution for injection. The administration is via infusion, with a maximum daily dose of 5.2 mg/kg and a total maximum dose of 124.8 mg/kg over 24 weeks.
**Caelyx**, with the active substance **doxorubicin hydrochloride**, is another comparator treatment. It is a pegylated liposomal 2 mg/ml concentrate for solution for infusion, provided by Baxter Holding B.V. The administration is through infusion, with a maximum daily dose of 40 mg/m² and a total maximum dose of 960 mg/m² over the treatment period.
Lastly, **GEMZAR**, containing **gemcitabine**, is provided by Lilly France as a 1000 mg powder for solution for infusion. The administration route is infusion, with a maximum daily dose of 1000 mg/m² and a total maximum dose of 24000 mg/m² over 24 weeks.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include **Progression-Free Survival (PFS)** and **Objective Response Rate (ORR)**, both evaluated per RECIST 1.1 criteria. Secondary endpoints encompass **Overall Survival (OS)**, **Duration of Response (DOR)** per RECIST 1.1, and the incidence and severity of adverse events (AEs) and clinical laboratory abnormalities as per NCI CTCAE V5.0. Additionally, changes from baseline to Week 8 (for q4w) or Week 9 (for q3w) in the score for the abdominal gastrointestinal symptoms subscale will be measured.
The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial. The use of validated scales and laboratory tests will ensure the accuracy and reliability of the data collected. The trial is designed to provide a comprehensive evaluation of the efficacy of luveltamab tazevibulin compared to investigator's choice chemotherapy in women with relapsed platinum-resistant epithelial ovarian cancer expressing folate receptor alpha (FOLR1).
Inclusion and Exclusion Criteria
Inclusion Criteria
- High grade serous epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer with pathology report documentation of tumor type.
- Age ≥ 18 years at the time of signing the informed consent form (ICF). If country/local age requirements define adulthood with a higher age, only subjects that meet the local age requirements may enroll in that specific country.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
- Life expectancy > 3 months.
- Positive FOLR1 expression per central laboratory testing.
- Relapsed platinum-resistant epithelial ovarian cancer and received a total of 1 to 3 regimens: a) Subjects who have only had 1 line of platinum-based therapy must have had a complete response (CR) or partial response (PR) and then progressed between ≥ 3 and < 6 months after the date of the last dose of platinum. b) Subjects who have received 2 or 3 lines of platinum therapy must have progressed in ≤ 6 months after the date of the last dose of platinum. c) Received ≤ 1 non-platinum regimen for platinum-resistant disease.
- Must be considered candidates for treatment with gemcitabine, paclitaxel, topotecan, or PLD for platinum resistant disease as per institutional standard of care.
- Prior bevacizumab treatment is required a) If labeled and available as standard of care per institutional guidelines b) Unless subject has documented contraindication to receive bevacizumab per bevacizumab label and institutional guidelines (eg, fistula, uncontrolled hypertension; to be discussed with and approved by the sponsor medical monitor or designee prior to enrollment).
- At least 1 radiographically measurable (Target) lesion per RECIST v1.1.
- Adequate bone marrow function defined as: a) Absolute neutrophil count (ANC) ≥ 1500/μL – use of growth factors to achieve this level is NOT permitted and must be stable off any growth factor within 3 weeks of first dose of study treatment. b) Hemoglobin ≥ 9 g/dL – use of growth factors or transfusion to achieve this level is NOT permitted and must be stable off any growth factor or post transfusion within 3 weeks of the first dose of study treatment. c) Platelet count ≥ 100 × 103/μL – transfusion to achieve this level is NOT permitted.
- Adequate liver function defined as: a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × upper limit of normal (ULN). b) Total bilirubin < 1.5 ULN • Subjects with known Gilbert disease: Total bilirubin ≤ 3.0 × ULN
- Adequate renal function defined as: • Creatinine clearance (CrCl) ≥ 30 mL/min
- Serum albumin ≥ 2.5 g/dL
- Calculated QT interval corrected for heart rate using Fridericia correction formula (QTcF), screening ECG and Cycle 1 Day 1 pre-dose ECG must be < 470 msec.
- Ability to comply with treatment, PK, and testing schedules.
- Subjects of childbearing potential must have a negative pregnancy test within 7 days of the first dose of study drug and be willing to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a < 1% failure rate while on treatment. All subjects must agree to avoid pregnancy and breastfeeding/nursing while on treatment and for ≥ 6 months after the last dose of luveltamab tazevibulin. A woman is not of childbearing potential if she has undergone surgical sterilization (total hysterectomy or bilateral oophorectomy or bilateral tubal ligation ≥ 6 weeks before taking study drug) or if she is post-menopausal and has had no menstrual bleeding of any kind including menstrual period, irregular bleeding, spotting, etc. for ≥ 12 months, with an appropriate clinical profile, and there is no other cause of amenorrhea (eg, hormonal therapy, prior chemotherapy). (Note: this inclusion criteria may be expanded/modified to ensure country/region specific requirements)
Exclusion Criteria
- Low grade (Grade 1) ovarian carcinoma.
- Clear cell, mucinous, endometrioid, sarcomatous, and mixed histology ovarian carcinomas.
- Prior treatment with a FOLR1-targeting ADCs (such as mirvetuximab and MORAB-202; irrespective of warhead type) or with ADCs that contain a tubulin inhibitor (eg, upifitamab rilsodotin, which contains auristatin derivative that inhibits tubulin polymerization).
- Primary platinum-refractory disease (no response [PR or CR] or disease progression < 3 months of completion of first line platinum-based chemotherapy).
- Greater than 3 lines of prior treatment.
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to antibody-related fusion protein treatment.
- Prior anti-cancer therapy (prior to first dose of study drug): • Chemotherapy ≤ 3 weeks, • PARPi ≤ 2 weeks, • Other therapeutic anti-cancer antibodies ≤ 3 weeks, • Radio- or toxin-immunoconjugates (eg, ADCs) ≤ 10 weeks, or • Radiation therapy/major surgery ≤ 2 weeks of first dose of study drug.
- Pre-existing clinically significant ocular disorders including, but not limited to: active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and/or monocular vision, keratitis, symptomatic cataracts with marked decrease in visual acuity (≥ Grade 3), keratitis, glaucoma, retinopathy, uveitis, and Sjogren syndrome. Subjects with myopia, “floaters”, and watering eyes are not excluded.
- Previous solid organ transplantation.
- Current signs/symptoms of bowel obstruction and/or signs/symptoms of bowel obstruction ≤ 3 months of initiation of study treatment
- Sensory or motor neuropathy > Grade 1.
- Residual CTCAE V5.0 ≥ Grade 2 toxicity from prior anticancer therapy, with the exception of Grade 2 alopecia and Grade 2 hypothyroidism due to previous cancer therapy.
- Subjects with past or current malignancy need to be discussed with the sponsor to determine eligibility. Examples of non exclusionary malignancies include: cervical carcinoma Stage 1A-1B (per Salib et al, 2020; FIGO 2018); non-invasive basal cell and squamous cell skin carcinoma; localized malignant melanoma with a CR of a duration of > 10 years; low risk, in situ breast cancer treated with curative intent; superficial noninvasive bladder cancer treated with curative intent.
- Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, and tuberculosis.
- Ongoing immunosuppressive therapy, including systemic corticosteroids. Note: Physiologic replacement and use of topical or inhaled corticosteroids are allowed. Dexamethasone may be used to treat chemotherapy induced nausea per institutional guidelines.
- Clinically significant cardiac disease including unstable angina, acute myocardial infarction ≤ 6 months of first dose of study drug or the following at screening: congestive heart failure (New York Heart Association Grade II or higher), left ventricle ejection fraction (LVEF) < 45% at baseline, and clinically significant arrhythmia. Exceptions which are allowed are asymptomatic stable atrial fibrillation for ≥ 6 months prior to study enrollment with sponsor approval. Extra systoles or minor conduction abnormalities are allowed.
- Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease.
- History or clinical signs of meningeal or active central nervous system involvement.
- History of severe COPD or active pneumonitis ≤ 6 months of the first dose of study drug. Subjects with a history of COPD or other lung disease that may limit pulmonary function require a pulmonary function test (PFT) at screening and are excluded with a FEV1 < 50% of predicted.
- History of stroke or significant cerebrovascular disease (ie, transient ischemic attack) ≤ 6 months of initiation of study treatment.
- Evidence of clinically significant third spacing (eg, pleural effusions, ascites, anasarca, etc.) that requires therapeutic intervention (paracentesis or pleurocentesis) within 8 weeks prior to the first dose of study drug.
- Known human immunodeficiency virus seropositivity.
- Females who are pregnant or breastfeeding, and all women of child-bearing potential unwilling to use a contraception method with a failure rate of < 1% while on treatment and for ≥ 6 months after last dose of luveltamab tazevibulin.
- Active hepatitis B or hepatitis C per Center for Disease Control guidelines and positive serology (unless due to vaccination or passive immunization due to immunoglobulin therapy with the following exceptions: a) Subject has had HCV but has received standard of care direct-acting antiviral treatment and achieved a sustained virologic response 12 weeks after completion of treatment (SVR12), with no detectable viral RNA. b) Subject has had HBV but is HBV surface antigen and viral DNA negative at screening. c) Subject has had HBV but received antiviral treatment and have undetectable viral DNA for 6 months prior to screening.
- Concurrent participation in another therapeutic treatment trial.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 31 May 2024 | 12 |
 Belgium | Not Recruiting | 31 May 2024 | 15 |
 Czechia | Not Recruiting | 31 May 2024 | 15 |
 Finland | Not Yet Recruiting | 31 May 2024 | 12 |
 Germany | Not Recruiting | 31 May 2024 | 35 |
 Hungary | Not Recruiting | 31 May 2024 | 9 |
 Ireland | Not Recruiting | 31 May 2024 | 15 |
 Italy | Not Recruiting | 31 May 2024 | 40 |
 Spain | Not Recruiting | 31 May 2024 | 40 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
HYCAMTIN 4 mg powder for concentrate for solution for infusion | Comparator | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INFUSION | 4 | 24 | PRD10109623 |
TAXOL 6 mg/ml, concentrato per soluzione per infusione. | Comparator | CONCENTRATO PER SOLUZIONE PER INFUSIONE | INFUSION | 80 | 24 | PRD9946309 |
Neulasta 6 mg solution for injection | Other | SOLUTION FOR INJECTION | INFUSION | 5.2 | 24 | PRD4042358 |
Caelyx pegylated liposomal 2 mg/ml concentrate for solution for infusion | Comparator | CONCENTRATE FOR SOLUTION FOR INFUSION | INFUSION | 40 | 24 | PRD9162744 |
GEMZAR 1000 mg, poudre pour solution pour perfusion | Comparator | POUDRE POUR SOLUTION POUR PERFUSION | INFUSION | 1000 | 24 | PRD324709 |