Upifitamab Rilsodotin Maintenance in Platinum-Sensitive Recurrent Ovarian Cancer (UP-NEXT)

Fallopian Tube Cancer Clinical Trial

— 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05329545
• Other study ID #: XMT-1536-3
• Status: Terminated
• Phase: Phase 3
• Start date: June 23, 2022
• Est. completion date: September 29, 2023

Study information

• Verified date: October 2023
• Source: Mersana Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 primary peritoneal cancer, expressing high levels of NaPi2b.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: September 29, 2023
• Est. primary completion date: September 29, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• High Grade Serous Ovarian Cancer
• Hypersensitivity
• Ovarian Neoplasms
• Primary Peritoneal Cancer

Intervention

Drug:
• Upifitimab rilsodotin
Upifitimab rilsodotin will be administered once every four weeks until completion, disease progression, unacceptable toxicity, voluntary discontinuation, or death (approximately up to 18 months).

Other:
• Placebo
Placebo controlled arm.

Locations

Country	Name	City	State
Australia	Epworth Richmond	Richmond	Victoria
Canada	Sherbrooke University Hospital Centre	Quebec	Sherbrooke
United States	Southwest Women's Oncology	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Texas Oncology P.A. - Austin	Austin	Texas
United States	Texas Oncology - DFWW	Bedford	Texas
United States	Billings Clinic	Billings	Montana
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center, Seidman Cancer Center	Cleveland	Ohio
United States	Karmanos Cancer Institute - Detroit	Detroit	Michigan
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Kettering Health Cancer Center	Kettering	Ohio
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	University of California Los Angeles, Gynecologic Oncology Clinic	Los Angeles	California
United States	University of Wisconsin Clinical Science Center	Madison	Wisconsin
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Methodist Hospital	Omaha	Nebraska
United States	University of California, Irvine Medical Center	Orange	California
United States	HonorHealth Research Institute - HonorHealth VGPCC Biltmore	Phoenix	Arizona
United States	Legacy Good Samaritan Medical Center - Legacy Medical Group - Gynecologic Oncology	Portland	Oregon
United States	Center of Hope	Reno	Nevada
United States	VCU Massey Cancer Center	Richmond	Virginia
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	WK Physicians	Shreveport	Louisiana
United States	Avera McKennan d/b/a Avera Research Institute	Sioux Falls	South Dakota
United States	Sanford Gynecologic Oncology	Sioux Falls	South Dakota
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Mersana Therapeutics	European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 12 months after the last dose for the last participant.
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to the date of death due to any cause.	Up to an average of 4 years. Follow up assessments for survival data will continue every 90 days following completion of treatment.
Secondary	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.	Up to 12 months after the last dose for the last participant.
Secondary	Adverse events (AEs) based on NCI CTCAE Version 5.0	Incidence and toxicity grade of AEs.	Up to 60 days past last dose
Secondary	Changes in Eastern Cooperative Oncology Group (ECOG) performance status	Assessment of ECOG performance status using ECOG performance scale.	Up to 60 days past last dose.
Secondary	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.	Up to 12 months after the last dose for the last participant.
Secondary	Number of participants using concomitant medications	Assessment of concomitant medication usage.	Up to 60 days past last dose.