Phase 3 Study Comparing Rinatabart Sesutecan Versus Investigator's Choice in Patients With Recurrent or Progressive Endometrial Cancer Following Platinum-Based and PD(L)-1 Therapy
- Trial ID
- 2024-519818-31-01
- Protocol
- GCT1184-03
- Sponsor
- Genmab A/S
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the clinical efficacy of rinatabart sesutecan against investigator's choice in patients with recurrent or progressive endometrial cancer following prior platinum-based chemotherapy and PD(L)-1 therapy. 5, 3
The secondary objectives include:
- Assessment of additional measures of efficacy.
- Evaluation of safety. 4
- Analysis of patient-reported outcomes.
Participants
This study involves 254 female participants diagnosed with endometrial cancer. The population consists of patients with recurrent or progressive disease, excluding subtypes such as neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma. Eligible individuals must have undergone between one and three prior lines of therapy, including previous exposure to platinum-based chemotherapy and a programmed death-ligand 1 inhibitor. Participants are required to have demonstrated radiographic progression on or after their most recent treatment regimen. The study population includes those who have received prior induction and maintenance therapy, where such sequences are categorized as a single line of treatment.
Plans and Procedures
This Phase 3, randomized, open-label study is designed to compare the efficacy and safety of rinatabart sesutecan against investigator's choice of therapy in patients with recurrent or progressive endometrial cancer. The study population includes individuals with histologically or cytologically confirmed disease, excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma, who have received between one and three prior lines of therapy, including platinum-based chemotherapy and a PD(L)-1 inhibitor. The primary endpoints are progression-free survival and overall survival, which will be assessed for up to approximately 3 years. Secondary endpoints include objective response rate, duration of response, treatment-emergent adverse events, and changes in quality of life. Clinical assessments are performed via independent central review using RECIST v1.1 criteria. The total study period is estimated to span from February 2026 to February 2029.
Treatment
The experimental medication is rinatabart sesutecan, provided as a solution for infusion. This substance is administered via intravenous infusion.
The comparator treatments consist of doxorubicin hydrochloride and paclitaxel. Doxorubicin hydrochloride is administered as an intravenous infusion at a dosage of 60 mg/m². Paclitaxel is administered as an intravenous infusion at a dosage of 80 mg/m².
Efficacy
The efficacy of rinatabart sesutecan will be evaluated using several primary and secondary endpoints. The primary endpoints include progression-free survival and overall survival, with assessments continuing for up to approximately 3 years. Progression-free survival is determined according to Response Criteria in Solid Tumors (RECIST) v1.1 via blinded independent central review.
Secondary efficacy parameters involve:
- Objective response rate as determined by both blinded independent central review and investigator assessment based on RECIST v1.1.
- Progression-free survival as determined by investigator assessment.
- Duration of response as determined by both investigator assessment and blinded independent central review using RECIST v1.1.
- Change from baseline in global health status/quality of life.
- Time to deterioration in global health status/quality of life.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants must have histologically or cytologically confirmed recurrent or progressive endometrial cancer (EC; any subtype excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma) following prior therapy.
- Participants must have received at least 1, but not more than 3, prior lines of therapy:
- Participants must have received prior platinum-based chemotherapy and a programmed death (ligand)-1 (PD(L)-1) inhibitor, either separately or in combination
- If the tumor recurred more than 12 months after completion of platinum-based chemotherapy, additional platinum-based chemotherapy must be administered for recurrent disease unless the participant is ineligible for further platinum-based chemotherapy, in which case the reason for ineligibility must be documented. Note: If Immunotherapy-based treatment is administered in the advanced / recurrent setting, then platinum rechallenge is not required, regardless of the duration of the platinum-free interval from prior platinum-based chemotherapy. In such cases, the reason for ineligibility for platinum-based chemotherapy must be documented.
- Prior induction plus maintenance is considered 1 line of therapy
- Hormonal therapy alone (ie, without chemotherapy) will not be counted as a separate line of therapy.
- Therapy changed due to toxicity in the absence of progression will be considered part of the same line of therapy (i.e., will not be counted independently as a separate line of therapy)
- Participants must have progressed radiographically on or after their most recent line of therapy
Exclusion Criteria
- Prior therapy with an antibody-drug conjugate containing a topoisomerase 1 inhibitor.
- Has a past or current malignancy other than the inclusion diagnosis before the planned 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 (eg, 5-year OS ≥90%), including, but not limited to, adequately treated cervical carcinoma of Stage 1B or less, noninvasive basal cell or squamous cell skin carcinoma, noninvasive superficial bladder cancer, ductal carcinoma in situ, or any past malignancy considered cured for ≥3 years (ie, eligible participants must have complete response of ≥3 years duration).
- 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 completion of 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 planned 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 15 May 2026 | 29 |
 Denmark | Recruiting | 15 May 2026 | 10 |
 Finland | Recruiting | 15 May 2026 | 13 |
 France | Recruiting | 15 May 2026 | 41 |
 Germany | Recruiting | 15 May 2026 | 52 |
 Greece | Recruiting | 15 May 2026 | 10 |
 Italy | Recruiting | 15 May 2026 | 48 |
 Lithuania | Recruiting | 15 May 2026 | 7 |
 Norway | Recruiting | 15 May 2026 | 7 |
 Poland | Recruiting | 15 May 2026 | 26 |
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 |
|---|---|---|---|---|---|---|
DOXORUBICIN | Comparator | PHF00231MIG | IV INFUSION | 60 | 36 | SCP119562649 |
Rinatabart Sesutecan | Test | SOLUTION FOR INFUSION | IV INFUSION | 0 | 36 | PRD11448868 |
PACLITAXEL | Comparator | PHF00230MIG | IV INFUSION | 80 | 36 | SCP129816 |