Clinical trial NCT05329545: Upifitamab Rilsodotin Maintenance in Platinum-Sensitive Recurrent Ovarian Cancer (UP-NEXT)
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Upifitamab Rilsodotin (XMT-1536) as Post-Platinum Maintenance Therapy for Participants With Recurrent, Platinum-Sensitive, Ovarian Cancer (UP-NEXT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: High Grade Serous Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Keywords: Ovarian Cancer
Serous
Maintenance
Antibody Drug Conjugate
Recurrent
Platinum-Sensitive
ADC
Fallopian Tube Cancer
Primary Peritoneal Cancer
Lead sponsor: Mersana Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: GOG Foundation
name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
First posted: 2022-04-15
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized, placebo controlled (2:1 upifitamab rilsodotin: placebo). Parallel cohorts.
Primary purpose: TREATMENT

Brief summary: UP-NEXT is a double-blind, randomized, placebo-controlled study of the antibody-drug conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once every four weeks in patients with recurrent, platinum-sensitive high-grade serous ovarian cancer (HGSOC), including fallopian tube and primary peritoneal cancer, expressing high levels of NaPi2b.

Detailed description: This is a multi-center randomized study of XMT-1536 (upifitamab rilsodotin) in patients with tumors expressing high levels of NaPi2b, focusing on patients with recurrent, platinum-sensitive high-grade serous ovarian cancer (HGSOC) including fallopian tube and primary peritoneal cancer. The randomized study design is a double-blind, placebo-controlled study, with a randomization ratio of 2:1. All adverse events will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria version (CTCAE v5.0). Participants must have had 4 to 8 cycles of platinum-based chemotherapy in their most recent treatment regimen, including carboplatin or cisplatin ± paclitaxel, docetaxel, pegylated liposomal doxorubicin or gemcitabine in the 2nd-4th line setting for the treatment of platinum-sensitive recurrent disease, with no evidence of disease (NED)/complete response (CR)/partial response (PR)/ or stable disease (SD) as best response.

Eligibility criteria: Inclusion Criteria:

1. Participant must have a histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube and primary peritoneal cancer, that is metastatic or recurrent.
2. Participant must have platinum-sensitive recurrent disease, defined as having achieved either a partial or complete response to 4 or more cycles in their penultimate platinum- containing regimen and their disease progressing more than 6 months after completion of the last dose of platinum containing therapy in the penultimate regimen.
3. Participant must have had 4 to 8 cycles of platinum-based chemotherapy in 2nd to 4th line setting in their most recent treatment regimen as defined below:

   1. Platinum-based chemotherapy regimens allowed immediately preceding enrollment to the study: carboplatin or cisplatin ±: paclitaxel, docetaxel, pegylated liposomal doxorubicin or gemcitabine.
   2. Participant must receive first study treatment infusion between 4 and 12 weeks after completing final dose of platinum in the most recent platinum-based regimen.
4. Participant must have had as their best response to last line of treatment one of the following: No Evidence of Disease (NED); Complete Response (CR); Partial Response (PR); OR Stable Disease (SD)
5. Participants with NED, CR, or PR as their best response to most recent line of treatment and who have not received treatment with a prior PARP inhibitor must have definitive BRCA1 and BRCA2 testing results that demonstrate no evidence of a deleterious BRCA1 or BRCA2 mutation. Somatic BRCA mutation testing is required for participants who are classified as not having a deleterious mutation by germline testing alone.
6. Participant must provide either a tumor tissue block or fresh cut slides for measurement of NaPi2b expression by a central laboratory. If sufficient archival tumor tissue is not available, then a tumor tissue block or slides must be obtained from a fresh biopsy and provided to the central laboratory. Confirmation of a NaPi2b-H/positive tumor by the central laboratory is required prior to randomization.

Exclusion Criteria:

1. Participant has received prior treatment with mirvetuximab soravtansine or another ADC containing an auristatin or maytansinoid payload.
2. Participant has received bevacizumab in combination with last platinum-based regiment or plans to receive maintenance therapy outside the study intervention.
3. Participant has clinical signs or symptoms of gastrointestinal obstruction and/or requirement for parenteral hydration or nutrition.
4. Participant has ascites or pleural effusion managed with therapeutic paracentesis or thoracentesis within 28 days prior to signing the principal study consent form.
5. Participant has history of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver disease. Testing beyond laboratory studies otherwise defined in the eligibility criteria, to diagnose potentially clinically significant liver disease based on risk factors such as hepatic steatosis or history of excessive alcohol intake, will be based on clinical judgement of the investigator.
6. Participant has history of or suspected pneumonitis or interstitial lung disease.
7. Participant has untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis, or carcinomatous meningitis.

Primary outcomes:
measure: Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Up to 12 months after the last dose for the last participant.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to an average of 4 years. Follow up assessments for survival data will continue every 90 days following completion of treatment.
measure: Progression-free Survival (PFS) as assessed by Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Up to 12 months after the last dose for the last participant.
measure: Adverse events (AEs) based on NCI CTCAE Version 5.0
timeFrame: Up to 60 days past last dose
measure: Changes in Eastern Cooperative Oncology Group (ECOG) performance status
timeFrame: Up to 60 days past last dose.
measure: Objective Response Rate (ORR) as assessed by Investigator using RECIST Version 1.1
timeFrame: Up to 12 months after the last dose for the last participant.
measure: Number of participants using concomitant medications
timeFrame: Up to 60 days past last dose.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: HonorHealth Research Institute - HonorHealth VGPCC Biltmore
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: University of California Los Angeles, Gynecologic Oncology Clinic
state: California
city: Orange
country: United States
facility: University of California, Irvine Medical Center
state: California
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Shreveport
country: United States
facility: WK Physicians
state: Louisiana
city: Detroit
country: United States
facility: Karmanos Cancer Institute - Detroit
state: Michigan
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Omaha
country: United States
facility: Methodist Hospital
state: Nebraska
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Reno
country: United States
facility: Center of Hope
state: Nevada
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Albuquerque
country: United States
facility: Southwest Women's Oncology
state: New Mexico
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Seidman Cancer Center
state: Ohio
city: Kettering
country: United States
facility: Kettering Health Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Medical Center - Legacy Medical Group - Gynecologic Oncology
state: Oregon
city: Willow Grove
country: United States
facility: Asplundh Cancer Pavilion
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Gynecologic Oncology
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera McKennan d/b/a Avera Research Institute
state: South Dakota
city: Austin
country: United States
facility: Texas Oncology P.A. - Austin
state: Texas
city: Bedford
country: United States
facility: Texas Oncology - DFWW
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Richmond
country: United States
facility: VCU Massey Cancer Center
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Clinical Science Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
city: Richmond
country: Australia
facility: Epworth Richmond
state: Victoria
city: Quebec
country: Canada
facility: Sherbrooke University Hospital Centre
state: Sherbrooke
Study officials:
affiliation: Mersana Therapeutics
name: Robert Burger, MD
role: STUDY_DIRECTOR
References: