Phase 3 Randomized Open-label Study of Rinatabart Sesutecan Versus Investigator's Choice in Platinum-Resistant Ovarian Cancer Patients
- Trial ID
- 2024-514822-21-00
- Protocol
- GCT1184-02
- Sponsor
- Genmab A/S
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3 randomized, open-label study is to compare **progression-free survival (PFS)** in patients with **platinum-resistant ovarian cancer (PROC)** receiving rinatabart sesutecan (Rina-S) versus the investigator’s choice of therapy (IC). This objective is clinically relevant as PFS is a critical endpoint in oncology trials, reflecting the time during which a patient's disease does not worsen, thus providing insights into the efficacy of Rina-S in managing PROC.
Secondary objectives include:
- To assess additional measures of efficacy of Rina-S compared to IC in patients with PROC.
- To assess the safety of Rina-S compared to IC in patients with PROC.
- To assess patient-reported outcomes in patients receiving Rina-S and IC.
Participants
The clinical trial involves a total of **361 participants** diagnosed with **platinum-resistant ovarian cancer**. The study population is exclusively female, with an age range that includes both adults and older adults. Participants were selected based on specific inclusion criteria, including a confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. The trial does not include a vulnerable population. Participants have previously undergone 1 to 4 lines of therapy, including platinum chemotherapy and bevacizumab treatment, where applicable. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial does not include male participants, and no information is provided regarding the general health status or lifestyle habits of the participants.
Plans and Procedures
The clinical trial is designed as a **randomized**, open-label study to evaluate the efficacy of rinatabart sesutecan (Rina-S) compared to the treatment of the investigator's choice in patients with **platinum-resistant ovarian cancer**. The primary objective is to compare progression-free survival (PFS) between the two groups. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), and other health-related quality of life measures. The trial is expected to commence recruitment on June 2, 2025, and conclude by May 31, 2029, with a maximum treatment period of 36 months for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed high-grade serous or endometrioid epithelial ovarian cancer and prior treatment history. Following randomization, participants will receive either Rina-S or the investigator's choice of therapy, which may include **paclitaxel**, **topotecan**, **doxorubicin hydrochloride**, or **gemcitabine hydrochloride**, administered via **intravenous infusion**. The study will involve regular follow-up visits to monitor treatment response and adverse events, with assessments based on RECIST version 1.1 criteria.
The expected length of participant involvement is up to 36 months, contingent upon disease progression or the occurrence of unacceptable toxicity. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with study procedures. The end-of-study visit will involve a comprehensive evaluation to assess the final outcomes and any long-term effects of the treatment. Throughout the trial, data will be collected to ensure the safety and efficacy of the investigational product, contributing to the overall understanding of treatment options for platinum-resistant ovarian cancer.
Treatment
The clinical trial involves the administration of **GEN1184 DP**, an experimental medication, which is a **human IgG1 kappa monoclonal antibody** against FOLR1 conjugated to a complex chemical structure. This investigational product is provided as a solution for infusion and is administered via **intravenous infusion**. The dosing schedule is determined by the investigator, with a maximum treatment period of 36 weeks. Participant compliance is monitored through regular assessments and documentation of infusion sessions.
**Glatiramer acetate**, also known as Copolymer-1, is included in the study as a comparator treatment. It is administered subcutaneously, with the pharmaceutical form coded as PHF00231MIG. The dosing regimen is tailored to the individual participant, with a focus on maintaining consistent administration throughout the trial period.
**Paclitaxel**, a chemical substance with synonyms such as Oncogel and ABI-007, is another comparator treatment. It is administered as an intravenous infusion, with a maximum daily dose of 80 mg/m². The pharmaceutical form is coded as PHF00230MIG, and the treatment period is capped at 36 weeks.
**Topotecan**, known by the synonym Nogitecan, is administered via intravenous infusion. The maximum daily dose is set at 4 mg/m², and the pharmaceutical form is coded as PHF00006MIG. The treatment duration is limited to 36 weeks, with dosing adjustments made based on participant response and tolerability.
**Doxorubicin hydrochloride** is included as a comparator treatment, administered through intravenous infusion. The maximum daily dose is 40 mg/m², and the pharmaceutical form is coded as PHF00231MIG. The treatment period is restricted to 36 weeks, with careful monitoring of participant compliance and response to therapy.
**Gemcitabine hydrochloride** is administered as an intravenous infusion, with a maximum daily dose of 1000 mg/m². The pharmaceutical form is coded as PHF00230MIG, and the treatment duration is set at 36 weeks. Participant adherence to the dosing schedule is closely monitored to ensure consistent therapeutic exposure.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is **Progression-Free Survival (PFS)**, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause, based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the investigator. Secondary endpoints include Overall Survival (OS), Objective Response Rate (ORR), Duration of Response (DOR), and the percentage of participants who achieve a Cancer Antigen-125 (CA-125) response per Gynecologic Cancer Intergroup (GCIG) criteria. Additional secondary endpoints involve Time to Second Disease Progression or Death (PFS2), overall change from baseline in Global Health Status/Quality of Life (GHS/QoL) using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC-QLQ-C30) questionnaire, Time to Deterioration (TTD) in the GHS/QoL score, and the number of participants with treatment-emergent adverse events (TEAEs) and laboratory abnormalities. Changes from baseline in electrocardiogram (ECG) findings to assess changes in QTc associated with Rina-S by Holter monitor will also be evaluated.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants must have histologically or cytologically confirmed high grade serous or endometrioid epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
- Participants may be enrolled regardless of FRα expression level.
- Participants must have received 1 to 4 prior lines of therapy. Patients must have progressed radiographically on or after their most recent line of therapy.
- Participants must have received prior treatment with the following therapies: • Platinum chemotherapy • Prior bevacizumab (or biosimilar) treatment is required, if labeled and available as standard of care per institutional guidelines, unless the participant has a documented contraindication or unless the patient is not eligible for treatment with bevacizumab (or biosimilar) due to precautions/intolerance • Participants with known or suspected deleterious germline or somatic breast cancer gene (BRCA) mutations and who achieved a complete or partial response to platinum-based chemotherapy must have been treated with a poly ADP-ribose polymerase (PARP) inhibitor as maintenance treatment unless the participant is not eligible for treatment with PARP inhibitor • Mirvetuximab soravtansine, if: • Mirvetuximab soravtansine is available in the enrollment region, and • The participant is eligible based on positive FRα expression per Food and Drug Administration (FDA)-approved (or local equivalent) test, and • The participant does not have a documented medical exception, including 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.
- Participants must have platinum-resistant disease: • Participants who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum therapy, and must have either had a response (CR or PR) or had non-measurable disease at the start of adjuvant platinum-based therapy, and then progressed between > 91 days and ≤ 183 days after the date of the last dose of platinum. • Participants who have received 2 to 4 lines of platinum-based therapy must have progressed on or within 183 days after the date of the last dose of platinum.
Exclusion Criteria
- Prior therapy with an antibody-drug conjugate containing a topoisomerase 1 inhibitor.
- Have primary platinum-refractory disease, defined as ovarian cancer that did not respond (CR or PR) to or progressed ≤ 91 days after the last dose of a first-line platinum-containing regimen.
- History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS ≥90%), including, but not limited to, adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, ductal carcinoma in situ, or Stage I uterine cancer.
- Known active central nervous system metastases or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry after brain metastasis treatment, they have no new or enlarging brain metastases, and are off corticosteroids and anticonvulsants prescribed for symptoms associated with brain metastases for at least 7 days prior to the first dose of study drug. Participants with suspected brain metastases at screening should undergo a computed tomography (CT)/magnetic resonance imaging (MRI) of the brain prior to study entry.
- Hospitalization or clinical symptoms due to gastrointestinal obstruction within the past 91 days or radiographic evidence of gastrointestinal obstruction at the time of screening. Enrollment of participants who currently require parenteral nutrition must be discussed with the study medical monitor to determine eligibility.
- Ascites requiring frequent paracentesis (more often than approximately every 4 weeks) for symptomatic management. Enrollment of participants with an indwelling peritoneal catheter must be discussed with the medical monitor to determine eligibility.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Recruiting | 02 Jun 2025 | 10 |
 Belgium | Recruiting | 02 Jun 2025 | 13 |
 Czechia | Recruiting | 02 Jun 2025 | 14 |
 Denmark | Recruiting | 02 Jun 2025 | 7 |
 France | Recruiting | 02 Jun 2025 | 14 |
 Germany | Recruiting | 02 Jun 2025 | 28 |
 Greece | Recruiting | 02 Jun 2025 | 11 |
 Italy | Recruiting | 02 Jun 2025 | 25 |
 The Netherlands | Recruiting | 02 Jun 2025 | — |
 Norway | Recruiting | 02 Jun 2025 | 5 |
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 |
|---|---|---|---|---|---|---|
PEGFILGRASTIM | Other | PHF00231MIG | SUBCUTANEOUS USE | 0.00 | 36 | SCP180112 |
PACLITAXEL | Comparator | PHF00230MIG | INTRAVENOUS INFUSION | 80.00 | 36 | SCP129816 |
DOXORUBICIN | Comparator | PHF00231MIG | INTRAVENOUS INFUSION | 40.00 | 36 | SCP138158 |
Rinatabart Sesutecan | Test | SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 0 | 36 | PRD11448868 |
GEMCITABINE | Comparator | PHF00230MIG | INTRAVENOUS INFUSION | 1000.00 | 36 | SCP1128788 |
TOPOTECAN | Comparator | PHF00006MIG | INTRAVENOUS INFUSION | 4.00 | 36 | SCP1673661 |