Clinical trial NCT06619236: Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Cancer
Official title: A Phase 3 Randomized, Open-label Study of Rinatabart Sesutecan (Rina-S) Versus Treatment of Investigator's Choice (IC) in Patients With Platinum Resistant Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Platinum-resistant Ovarian Cancer
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
Lead sponsor: Genmab
Sponsor class: INDUSTRY
First posted: 2024-10-01
Enrollment: 530
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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 received prior treatment with the following therapies:

  * Platinum chemotherapy
  * Prior bevacizumab treatment is required, if labeled and available as standard of care per institutional guidelines, unless the participant has a documented contraindication or 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 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.

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.
* 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.

NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 5 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 5 years
measure: Percentage of Participants Who Achieved Cancer Antigen-125 (CA-125) Response per Gynecologic Cancer Intergroup (GCIG) Criteria
timeFrame: Up to approximately 5 years
measure: Time to Second Disease Progression or Death From any Cause (PFS2)
timeFrame: Up to approximately 5 years
measure: Overall Change From Baseline in Global Health Status/Quality of Life (GHS/Qol)
timeFrame: Baseline, up to approximately 5 years
measure: Time to Deterioration (TTD) in the GHS/Qol Score
timeFrame: Up to approximately 5 years
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Laboratory Abnormalities
timeFrame: From first dose until the end of the study (approximately 5 years)
measure: Change from Baseline in Electrocardiogram (ECG) Findings to Assess Changes in QTc Associated with Rina-S by Holter Monitor
timeFrame: Baseline through Cycle 1 (Cycle length=21 days)
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Women's Cancer Care
state: Alaska
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Roy and Patricia Disney Family Cancer Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: USCF Mission Bay
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Orlando
country: United States
facility: Orlando Health Cancer Institute - Downtown Orlando
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: West Palm Beach
country: United States
facility: SCRI - Florida Cancer Specialists - West Palm Beach
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Dyer
country: United States
facility: Northwest Cancer Center - Dyer
state: Indiana
city: Overland Park
country: United States
facility: HCA Midwest Health
state: Kansas
city: Edgewood
country: United States
facility: St. Elizabeth Healthcare - Edgewood
state: Kentucky
city: Shreveport
country: United States
facility: Trials365, LLC (Gynecologic Oncology Associates-Shreveport)
state: Louisiana
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Ypsilanti
country: United States
facility: Saint Joseph Mercy Ann Arbor Hospital
state: Michigan
city: Reno
country: United States
facility: Center of Hope
state: Nevada
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: New York
country: United States
facility: Perlmutter Cancer Center - 38th Street
state: New York
city: New York
country: United States
facility: Perlmutter Cancer Center at NYU Langone Hospital - Long Island
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Outpatient Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Hilliard
country: United States
facility: JamesCare Gynecologic Oncology at Mill Run
state: Ohio
city: Portland
country: United States
facility: Legacy Good Samaritan Medical Center
state: Oregon
city: Portland
country: United States
facility: USOR - Northwest Cancer Specialists, P.C. dba Compass Oncology - Rose Quarter Cancer Center
state: Oregon
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Abilene
country: United States
facility: USOR - Texas Oncology - Dallas Fort Worth (DFW) - Abilene
state: Texas
city: Austin
country: United States
facility: USOR - Texas Oncology - Dallas Fort Worth (DFW) - Austin Central
state: Texas
city: Fort Worth
country: United States
facility: USOR - Texas Oncology - Dallas Fort Worth (DFW) - Fort Worth
state: Texas
city: Norfolk
country: United States
facility: USOR - Virginia Oncology Associates - Norfolk
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University Cancer Institute
state: West Virginia
city: Hidaka
country: Japan
facility: Saitama Medical University - International Medical Center
state: Saitama
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Cancer Institute Hospital of JFCR
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: