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

NCT05329545 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: XMT-1536-3
• Study Type: interventional
• Target: 20
• Locations: 3 countries
• Sites: 30

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall Survival (OS)

  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

  Up to 12 months after the last dose for the last participant.

• Adverse events (AEs) based on NCI CTCAE Version 5.0

  Up to 60 days past last dose

• Changes in Eastern Cooperative Oncology Group (ECOG) performance status

  Up to 60 days past last dose.

• Objective Response Rate (ORR) as assessed by Investigator using RECIST Version 1.1

  Up to 12 months after the last dose for the last participant.

Study Arms (2)

XMT-1536 (upifitamab rilsodotin)

EXPERIMENTAL

XMT-1536 (upifitamab rilsodotin)

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.

Other: Placebo

Interventions

Upifitimab rilsodotin DRUG

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

Also known as: XMT-1536 Antibody Drug Conjugate

XMT-1536 (upifitamab rilsodotin)

Placebo OTHER

Placebo controlled arm.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mersana Therapeutics: lead
• GOG Foundation: collaborator
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator

Study Sites (30)

HonorHealth Research Institute - HonorHealth VGPCC Biltmore

Phoenix, Arizona, 85016, United States

Location

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

University of California Los Angeles, Gynecologic Oncology Clinic

Los Angeles, California, 90095, United States

Location

University of California, Irvine Medical Center

Orange, California, 92868, United States

Location

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

WK Physicians

Shreveport, Louisiana, 71103, United States

Location

Karmanos Cancer Institute - Detroit

Detroit, Michigan, 48201, United States

Location

Billings Clinic

Billings, Montana, 59101, United States

Location

Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Women's Cancer Center of Nevada

Las Vegas, Nevada, 89106, United States

Location

Center of Hope

Reno, Nevada, 89433, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Southwest Women's Oncology

Albuquerque, New Mexico, 87109, United States

Location

University Hospitals Cleveland Medical Center, Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Kettering Health Cancer Center

Kettering, Ohio, 45429, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

Location

Legacy Good Samaritan Medical Center - Legacy Medical Group - Gynecologic Oncology

Portland, Oregon, 97210, United States

Location

Asplundh Cancer Pavilion

Willow Grove, Pennsylvania, 19090, United States

Location

Sanford Gynecologic Oncology

Sioux Falls, South Dakota, 57104, United States

Location

Avera McKennan d/b/a Avera Research Institute

Sioux Falls, South Dakota, 57105, United States

Location

Texas Oncology P.A. - Austin

Austin, Texas, 78745, United States

Location

Texas Oncology - DFWW

Bedford, Texas, 76022, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

VCU Massey Cancer Center

Richmond, Virginia, 23291, United States

Location

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

Location

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Epworth Richmond

Richmond, Victoria, 3121, Australia

Location

Sherbrooke University Hospital Centre

Québec, Sherbrooke, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Robert Burger, MD

  Mersana Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, randomized, placebo controlled (2:1 upifitamab rilsodotin: placebo). Parallel cohorts.

Study Record Dates

• First Submitted: March 24, 2022
• First Posted: April 15, 2022
• Study Start: June 23, 2022
• Primary Completion: September 29, 2023
• Study Completion: September 29, 2023
• Last Updated: October 26, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); US (28); CA (1)