Platinum-resistant Ovarian Cancer
Conditions
Keywords
antibody-drug conjugate, folate receptor alpha (FRα), ovarian cancer, fallopian tube cancer, primary peritoneal cancer, folate receptor, platinum-resistant ovarian cancer (PROC), rinatabart sesutecan, Topoisomerase 1 inhibitor, PRO1184, GEN1184
Brief summary
This phase 3 study will be conducted in different countries all over the world. The purpose of this study is to compare how well Rina-S works against platinum-resistant ovarian cancer compared to chemotherapy drugs that are already approved and used for platinum-resistant ovarian cancer. Treatment in this study could be Rina-S or it could be 1 of 4 indicated chemotherapy agents that are considered standard medical care. There is an equal (50:50) chance of getting Rina-S or an approved chemotherapy agent as treatment in this study. No one will know what treatment they are assigned to until the first dose. All participants will receive active drug; no one will be given placebo.
Interventions
DRUGRina-S
Intravenous (IV) infusion
DRUGPaclitaxel
IV infusion
DRUGTopotecan
IV infusion
DRUGPegylated liposomal doxorubicin (PLD)
IV infusion
DRUGGemcitabine
IV infusion
Sponsors
Genmab
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
Key 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. Participants 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 participant 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, 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 a protocol defined number of lines of platinum-based therapy must have progressed on or within 183 days after the date of the last dose of platinum. Key
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. * Participant has clinically significant ascites/pleural effusion. Enrollment of participants with an indwelling catheter flush/drain is not allowed. Note: Clinically significant is defined as (1) symptomatic, or (2) requires therapeutic paracentesis/thoracentesis within 8 weeks of the first dose, or (3) recurrent ascites/pleural effusion that necessitates multiple paracentesis/thoracocentesis procedures more often than approximately every 4 weeks. NOTE: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 1.5 years | PFS is defined as the time from the date of randomization to the date of the first documented progression or death (PD) due to any cause, whichever occurs first based on response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 1.5 years | OS is defined as the time from date of randomization to date of death due to any cause. |
| Objective Response Rate (ORR) | Up to approximately 1.5 years | ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on RECIST v1.1 as assessed by the investigator. |
| PFS as Determined by BICR | Up to approximately 1.5 years | PFS is defined as the time from the date of randomization to the date of the first documented progression or death (PD) due to any cause, whichever occurs first based on RECIST version 1.1 as determined by BICR. |
| ORR as Determined by BICR | Up to approximately 1.5 years | ORR is defined as the percentage of participants with BOR of CR or PR based on RECIST v1.1 as determined by BICR. |
| Duration of Response (DOR) | Up to approximately 1.5 years | DOR is defined as the time from the onset date of response to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by the investigator and by blinded independent central review (BICR). |
| Percentage of Participants Who Achieved Cancer Antigen-125 (CA-125) Response per Gynecologic Cancer Intergroup (GCIG) Criteria | Up to approximately 1.5 years | A CA-125 response per the GCIG criteria is defined as a ≥ 50% reduction in CA-125 levels from baseline. |
| Time to Second Disease Progression or Death From any Cause (PFS2) | Up to approximately 1.5 years | PFS2 is defined as the time from randomization to the date of the second PD (i.e., the first PD reported in subsequent anti-cancer therapies, or long-term follow up) or death. |
| Overall Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) | Baseline, up to approximately 1.5 years | Overall change from baseline in GHS/Qol score (items 29 and 30) will be calculated using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC-QLQ-C30) questionnaire. The score ranges from 0 to 100. A high scale score represents a higher response level. |
| Time to Deterioration (TTD) in the GHS/Qol Score | Up to approximately 1.5 years | TTD in the GHS/Qol score is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) in GHS/QoL score. A longer TTD indicates a better outcome. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to approximately 1.5 years | — |
| Change from Baseline in Electrocardiogram (ECG) Findings to Assess Changes in QTc Associated with Rina-S by Holter Monitor | Baseline through Cycle 3 (Cycle length=21 days) | — |
Countries
Australia, Austria, Belgium, Canada, China, Czechia, Denmark, France, Germany, Greece, Italy, Japan, Netherlands, Norway, Poland, Puerto Rico, Spain, United States
Contacts
STUDY_DIRECTORStudy Official
Genmab
Outcome results
None listed