High Grade Serous Ovarian CancerPhase 3UP-NEXTNCT05329545
Upifitamab Rilsodotin Maintenance in Platinum-Sensitive Recurrent Ovarian Cancer (UP-NEXT)
A Phase 3 study testing Upifitimab rilsodotin in people with High Grade Serous Ovarian Cancer and Fallopian Tube Cancer, run by Mersana Therapeutics at 30 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- High Grade Serous Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer
- What is being tested?
- Upifitimab rilsodotin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 30 sitesin 3 countries
- Study dates
- 23 Jun 2022to 29 Sep 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- 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:
- Platinum-based chemotherapy regimens allowed immediately preceding enrollment to the study: carboplatin or cisplatin ±: paclitaxel, docetaxel, pegylated liposomal doxorubicin or gemcitabine.
- 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.
- 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)
- 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.
- 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.
Who cannot join
- Participant has received prior treatment with mirvetuximab soravtansine or another ADC containing an auristatin or maytansinoid payload.
- Participant has received bevacizumab in combination with last platinum-based regiment or plans to receive maintenance therapy outside the study intervention.
- Participant has clinical signs or symptoms of gastrointestinal obstruction and/or requirement for parenteral hydration or nutrition.
- Participant has ascites or pleural effusion managed with therapeutic paracentesis or thoracentesis within 28 days prior to signing the principal study consent form.
- 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.
- Participant has history of or suspected pneumonitis or interstitial lung disease.
- Participant has untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis, or carcinomatous meningitis.
Trial locations and contacts
30 sites in 3 countries.
30 sites in 3 countries
United States28 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Southwest Women's Oncology
Albuquerque, New Mexico, 87109
Texas Oncology P.A. - Austin
Austin, Texas, 78745
Texas Oncology - DFWW
Bedford, Texas, 76022
Billings Clinic
Billings, Montana, 59101
University of Chicago Medical Center
Chicago, Illinois, 60637
University Hospitals Cleveland Medical Center, Seidman Cancer Center
Cleveland, Ohio, 44106
Karmanos Cancer Institute - Detroit
Detroit, Michigan, 48201
Willamette Valley Cancer Institute and Research Center
Eugene, Oregon, 97401
Kettering Health Cancer Center
Kettering, Ohio, 45429
Women's Cancer Center of Nevada
Las Vegas, Nevada, 89106
University of California Los Angeles, Gynecologic Oncology Clinic
Los Angeles, California, 90095
University of Wisconsin Clinical Science Center
Madison, Wisconsin, 53792
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Methodist Hospital
Omaha, Nebraska, 68114
University of California, Irvine Medical Center
Orange, California, 92868
HonorHealth Research Institute - HonorHealth VGPCC Biltmore
Phoenix, Arizona, 85016
Legacy Good Samaritan Medical Center - Legacy Medical Group - Gynecologic Oncology
Portland, Oregon, 97210
Center of Hope
Reno, Nevada, 89433
VCU Massey Cancer Center
Richmond, Virginia, 23291
Sarasota Memorial Hospital
Sarasota, Florida, 34239
WK Physicians
Shreveport, Louisiana, 71103
Sanford Gynecologic Oncology
Sioux Falls, South Dakota, 57104
Avera McKennan d/b/a Avera Research Institute
Sioux Falls, South Dakota, 57105
The University of Arizona Cancer Center
Tucson, Arizona, 85719
Texas Oncology - Tyler
Tyler, Texas, 75702
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090
About this study
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)
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.
Read the 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.
- Being tested
- Upifitimab rilsodotin, Placebo
- Keywords
- Ovarian Cancer, Serous, Maintenance, Antibody Drug Conjugate, Recurrent, Platinum-Sensitive, ADC, Fallopian Tube Cancer, Primary Peritoneal Cancer
- Medical subject headings
- Fallopian Tube Neoplasms, Ovarian Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Upifitimab rilsodotinDrug
Also called XMT-1536 Antibody Drug Conjugate
Upifitimab rilsodotin will be administered once every four weeks until completion, disease progression, unacceptable toxicity, voluntary discontinuation, or death (approximately up to 18 months).
PlaceboOther
Placebo controlled arm.
| Study group | Role | What they receive |
|---|---|---|
| XMT-1536 (upifitamab rilsodotin) | Experimental | XMT-1536 (upifitamab rilsodotin) Receives: Drug: Upifitimab rilsodotin |
| Placebo | Placebo comparator | Saline placebo will be administered with same schedule and stopping rules as for the assigned interventions in the Experimental Arm. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS is defined as the time from randomization to the earliest date of progressive disease as assessed by BICR per RECIST Version 1.1 or death due to any cause.
Measured: Up to 12 months after the last dose for the last participant.
Secondary outcomes (6)
Overall Survival (OS)
OS is defined as the time from randomization to the date of death due to any cause.
Measured: Up to an average of 4 years. Follow up assessments for survival data will continue every 90 days following completion of treatment.
Progression-free Survival (PFS) as assessed by Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS is defined as the time from randomization to the earliest date of progressive disease as assessed by Investigator per RECIST Version 1.1 or death due to any cause.
Measured: Up to 12 months after the last dose for the last participant.
Adverse events (AEs) based on NCI CTCAE Version 5.0
Incidence and toxicity grade of AEs.
Measured: Up to 60 days past last dose
Changes in Eastern Cooperative Oncology Group (ECOG) performance status
Assessment of ECOG performance status using ECOG performance scale.
Measured: Up to 60 days past last dose.
Objective Response Rate (ORR) as assessed by Investigator using RECIST Version 1.1
ORR is the percentage of patients achieving a confirmed complete response (CR) or partial response (PR) as assessed by Investigator per RECIST Version 1.1.
Measured: Up to 12 months after the last dose for the last participant.
Number of participants using concomitant medications
Assessment of concomitant medication usage.
Measured: Up to 60 days past last dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2022
- Study start23 Jun 2022
- Primary completion29 Sep 2023
- Study completion29 Sep 2023
Why it stopped: Study Terminated by Sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Grade Serous Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, randomized, placebo controlled (2:1 upifitamab rilsodotin: placebo). Parallel cohorts.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mersana Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GOG Foundation, European Network of Gynaecological Oncological Trial Groups (ENGOT)
- Responsible party
- Sponsor
- Investigators
- Robert Burger, MD, Study director, Mersana Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05329545
- Sponsor's protocol ID
- XMT-1536-3
- Acronym
- UP-NEXT
- Status last verified
- Oct 2023
- First submitted
- 24 Mar 2022
- Last updated
- 26 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05329545
- Acronym / sponsor ID
- UP-NEXT / XMT-1536-3
- Keywords
- Ovarian Cancer, Serous, Maintenance, Antibody Drug Conjugate, Recurrent, Platinum-Sensitive, ADC, Fallopian Tube Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study Terminated by Sponsor
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Mersana TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- GOG Foundation, European Network of Gynaecological Oncological Trial Groups (ENGOT)
- Study start
- 23 Jun 2022 (actual)
- Primary completion
- 29 Sep 2023 (actual)
- Study completion
- 29 Sep 2023 (actual)
- First posted
- 15 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, randomized, placebo controlled (2:1 upifitamab rilsodotin: placebo). Parallel cohorts.
| Arm | Type | Receives |
|---|---|---|
| XMT-1536 (upifitamab rilsodotin) | Experimental | Drug: Upifitimab rilsodotinXMT-1536 (upifitamab rilsodotin) |
| Placebo | Placebo comparator | Other: PlaceboSaline placebo will be administered with same schedule and stopping rules as for the assigned interventions in the Experimental Arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- 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.
- 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:
- 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)
- 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.
Key exclusion criteria (7 listed)
- Participant has received prior treatment with mirvetuximab soravtansine or another ADC containing an auristatin or maytansinoid payload.
- Participant has received bevacizumab in combination with last platinum-based regiment or plans to receive maintenance therapy outside the study intervention.
- Participant has clinical signs or symptoms of gastrointestinal obstruction and/or requirement for parenteral hydration or nutrition.
- Participant has ascites or pleural effusion managed with therapeutic paracentesis or thoracentesis within 28 days prior to signing the principal study consent form.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Upifitimab rilsodotinAlso: XMT-1536 Antibody Drug ConjugateUpifitimab rilsodotin will be administered once every four weeks until completion, disease progression, unacceptable toxicity, voluntary discontinuation, or death (approximately up to 18 months). | Drug | XMT-1536 (upifitamab rilsodotin) |
| PlaceboPlacebo controlled arm. | Other | Placebo |
Primary outcome
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: Up to 12 months after the last dose for the last participant.
PFS is defined as the time from randomization to the earliest date of progressive disease as assessed by BICR per RECIST Version 1.1 or death due to any cause.
6 secondary outcomes
Overall Survival (OS)
Time frame: Up to an average of 4 years. Follow up assessments for survival data will continue every 90 days following completion of treatment.
Progression-free Survival (PFS) as assessed by Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: Up to 12 months after the last dose for the last participant.
Adverse events (AEs) based on NCI CTCAE Version 5.0
Time frame: Up to 60 days past last dose
Changes in Eastern Cooperative Oncology Group (ECOG) performance status
Time frame: Up to 60 days past last dose.
Objective Response Rate (ORR) as assessed by Investigator using RECIST Version 1.1
Time frame: Up to 12 months after the last dose for the last participant.
Number of participants using concomitant medications
Time frame: Up to 60 days past last dose.
Results and safety
The study was stopped early (reason given: Study Terminated by Sponsor). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Burger, MD study director
Mersana Therapeutics
30 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Upifitimab rilsodotin in people with High Grade Serous Ovarian Cancer and Fallopian Tube Cancer, run by Mersana Therapeutics at 30 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study Terminated by Sponsor). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (time frame: Up to 12 months after the last dose for the last participant.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2023.