Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator’s Choice in Participants With Platinum Resistant Ovarian Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genmab A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Oct 2025 → ongoing

Decision date (initial)

2025-05-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Genmab A/S

External identifiers

EU CT number

2024-514822-21-00

ClinicalTrials.gov

NCT06619236

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Therapy

To compare progression-free-survival (PFS) in patients with platinum-resistant ovarian cancer (PROC) receiving rinatabart sesutecan (Rina-S) versus investigator’s choice of therapy (IC)

Secondary objectives 3

1. 1. To assess additional measures of efficacy of Rina-S compared to IC in patients with PROC
2. 2. To assess the safety of Rina-S compared to IC in patients with PROC
3. 3. To assess patient reported outcomes in patients receiving Rina-S and IC

Conditions and MedDRA coding

Platinum-resistant Ovarian Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Participants must have histologically or cytologically confirmed high grade serous or endometrioid epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
2. 2. Participants may be enrolled regardless of FRα expression level.
3. 3. 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.
4. 4. 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.
5. 5. 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 6

1. 1. Prior therapy with an antibody-drug conjugate containing a topoisomerase 1 inhibitor.
2. 2. 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.
3. 3. 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.
4. 4. 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.
5. 5. 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.
6. 6. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-Free Survival (PFS) 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 endpoints 10

1. 1. Overall Survival (OS) OS is defined as the time from date of randomization to date of death due to any cause.
2. 2. Objective Response Rate (ORR) 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.
3. 4. Duration of Response (DOR) 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 BICR.
4. 5. Percentage of Participants Who Achieved Cancer Antigen-125 (CA-125) Response per Gynecologic Cancer Intergroup (GCIG) Criteria A CA-125 response per the GCIG criteria is defined as a ≥ 50% reduction in CA-125 levels from baseline.
5. 6. Time to Second Disease Progression or Death From any Cause (PFS2) 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.
6. 9. Overall Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) 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.
7. 10. Time to Deterioration (TTD) in the GHS/Qol Score 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.
8. 7. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Laboratory Abnormalities
9. 8. Change From Baseline in Electrocardiogram (ECG) Findings to Assess Changes in QTc Associated with Rina-S by Holter Monitor
10. 3. Progression Free Survival (PFS) and ORR, per RECIST v1.1, as determined by blinded independent central review (BICR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 4

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genmab A/S

Sponsor organisation

Genmab A/S

Address

Carl Jacobsens Vej 30

City

Valby

Postcode

2500

Country

Denmark

Scientific contact point

Organisation

Genmab A/S

Contact name

Genmab Trial Information

Public contact point

Organisation

Genmab A/S

Contact name

Genmab Trial Information

Third parties 16

Locations

12 EU/EEA countries · 84 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 110 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications