First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b

A Phase 1b/2, First-in-Human, Dose Escalation and Expansion Study of XMT-1536 In Patients With Solid Tumors Likely to Express NaPi2b

First-in-human, Phase 1b/2 safety study of the antibody-drug conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once every four weeks. Patients with tumor types likely to express NaPi2b were enrolled in dose escalation. Patients with platinum-resistant ovarian cancer and non-small cell lung cancer (adenocarcinoma subtype) were enrolled in the expansion segment of this study. Patients with platinum-resistant, high-grade serous ovarian cancer are being enrolled in the UPLIFT segment of this study. In addition to safety assessments, the pharmacokinetics of the drug will be assessed along with ADC activity. A QTc sub-study has been added for the UPLIFT cohort for a sub-set of sites.

Study Overview

• Status: Recruiting
• Conditions: Platinum Resistant Ovarian Cancer; Non Small Cell Lung Cancer Metastatic
• Intervention / Treatment: Drug: upifitamab rilsodotin

Detailed Description

This is a multi-center study of XMT-1536 (upifitamab rilsodotin) in patients with tumors likely to express NaPi2b, focusing on patients with platinum-resistant ovarian cancer and non-small cell lung cancer, adenocarcinoma subtype. XMT-1536 (upifitamab rilsodotin) will be administered as an intravenous infusion once every four weeks. The study consists of three segments: dose escalation (DES), dose expansion (EXP), and the pivotal cohort (UPLIFT). The DES segment studied small groups of patients who received increased doses. A Safety Review Committee was established to review the data from each dose level before moving to the next higher dose. The dose escalation cohort has ended and is no longer enrolling patients. Enrollment into the EXP segment consists of 2 parallel cohorts of patients to confirm the dose that has been identified in DES and estimate the objective response rate in each patient population. The EXP cohort is no longer enrolling patients. Enrollment into the pivotal cohort (UPLIFT) includes patients with platinum-resistant ovarian cancer. All adverse events will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria version (CTCAE v5.0). Throughout the study, pharmacokinetics will be measured using proprietary assays developed by Mersana. Anti-cancer activity will be measured via RECIST.

• Study Type: Interventional
• Enrollment (Anticipated): 444
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jamie Barrett; Phone Number: 617-715-8214; Email: medicalinformation@mersana.com

Study Locations

• Australia
  • Blacktown, Australia, 2148
    • Active, not recruiting
    • Blacktown Road
  • Camperdown, Australia, 2050
    • Active, not recruiting
    • Chris OBrien Lifehouse
  • Camperdown, Australia
    • Active, not recruiting
    • Chris O'Brien Lifehouse
  • Herston, Australia, 4029
    • Withdrawn
    • Royal Brisbane and Women's Hospital
  • Melbourne, Australia, 3000
    • Active, not recruiting
    • Peter MacCallum Cancer Center
  • South Brisbane, Australia, 4201
    • Active, not recruiting
    • Icon Cancer Centre South Brisbane
  • Victoria
    • Heidelberg, Victoria, Australia
      • Withdrawn
      • Austin Health - Olivia Newton John Cancer Center
• Austria
  • Graz, Austria, 8036
    • Active, not recruiting
    • University Hospital Graz
  • Innsbruck, Austria, 6020
    • Active, not recruiting
    • University Hospital Innsbruck - Tyrolean Hospital
• Belgium
  • Aalst, Belgium, 9300
    • Active, not recruiting
    • Our Dear Lady Hospital, Aalst Campus
  • Brussel, Belgium, 1200
    • Active, not recruiting
    • Saint Luc University Hospital
  • Kortrijk, Belgium, 8500
    • Active, not recruiting
    • Campus Kennedylaan, President Kennedylaan 4
  • Leuven, Belgium, 3000
    • Active, not recruiting
    • Herestraat 49
  • Liège, Belgium, 4000
    • Active, not recruiting
    • Avenue de l'Hopital 1
• Bulgaria
  • Branipole, Bulgaria, 4109
    • Active, not recruiting
    • Multiprofile Hospital for Active Treatment" Park Hospital EOOD
  • Burgas, Bulgaria, 8000
    • Active, not recruiting
    • Complex Oncology Center - Burgas
  • Sofia, Bulgaria, 1303
    • Active, not recruiting
    • Multiprofile Hospital for Active Treatment "Serdika", Sofia
  • Sofia, Bulgaria, 1330
    • Active, not recruiting
    • MHAT for Women's Health "Nadezhda"
  • Sofia, Bulgaria, 1797
    • Active, not recruiting
    • Multiprofile Hospital for Active Treatment "Sofiamed", Sofia
  • Sofia, Bulgaria, 4500
    • Active, not recruiting
    • Multiprofile Hospital for Active Treatment - Uni Hospital, Panagyurishte
• Canada
  • Calgary, Canada, T2N 4N2
    • Active, not recruiting
    • Tom Baker Cancer Center
  • Québec, Canada, J1G 2E8
    • Active, not recruiting
    • Sherbrooke University Hospital Centre
  • Toronto, Canada, M5G 2M9
    • Active, not recruiting
    • Princess Margaret Cancer Centre
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Active, not recruiting
      • British Columbia Cancer Agency
  • Quebec
    • Montreal, Quebec, Canada
      • Active, not recruiting
      • McGill University Health Centre - The Montreal General Hospital
• Czechia
  • Brno, Czechia, 625 00
    • Active, not recruiting
    • University Hospital Brno
  • Prague, Czechia, 110 00
    • Active, not recruiting
    • General University Hospital in Prague
  • Prague, Czechia, 180 81
    • Active, not recruiting
    • University Hospital Bulovka
• Denmark
  • Copenhagen, Denmark, DK-2100
    • Active, not recruiting
    • Rigshospitalet - University Hospital Copenhagen
  • Odense, Denmark, DK-5230
    • Active, not recruiting
    • Odense University Hospital
• Finland
  • Tampere, Finland, 33520
    • Active, not recruiting
    • Tampere University Hospital
• France
  • Caen, France, 14076
    • Active, not recruiting
    • François Baclesse Center
  • Montpellier, France, 34298
    • Active, not recruiting
    • Léon Bérard Center
  • Montpellier, France, 34298
    • Active, not recruiting
    • Montpellier Cancer Institute
  • Nantes, France, 44277
    • Active, not recruiting
    • Confluent Private Hospital
  • Pierre-Bénite, France, 69495
    • Active, not recruiting
    • South Lyon Hospital Center, Department of Clinical Hematology
  • Strasbourg, France, 23025
    • Withdrawn
    • Strasbourg Europe Institut of Cancerology
  • Toulouse, France, 31059
    • Active, not recruiting
    • Institute Claudius Regaud
  • Villejuif, France, 94805
    • Active, not recruiting
    • Gustave Roussy
• Hungary
  • Budapest, Hungary, 1122
    • Active, not recruiting
    • National Institute of Oncology
  • Debrecen, Hungary, 4032
    • Active, not recruiting
    • University of Debrecen Clinical Center
  • Győr, Hungary, 9024
    • Active, not recruiting
    • Petz Aladár University Teaching Hospital
• Italy
  • Bologna, Italy, 40138
    • Withdrawn
    • Polyclinic S. Orsola-Malpighi
  • Catania, Italy, 95126
    • Active, not recruiting
    • Hospital Cannizzaro - Catania
  • Milan, Italy, 20132
    • Active, not recruiting
    • Hospital San Raffaele, IRCCS
  • Naples, Italy, 80131
    • Active, not recruiting
    • National Cancer Institute - IRCCS "Fondazione G. Pascale"
  • Rome, Italy, 00128
    • Active, not recruiting
    • University Hospital Campus Bio-Medico
  • Rome, Italy, 00144
    • Active, not recruiting
    • National Cancer Institute Regina Elena, IRCCS
  • Rome, Italy, 00168
    • Active, not recruiting
    • University Polyclinic Foundation "Agostino Gemelli" - IRCCS
  • Turin, Italy, 10060
    • Withdrawn
    • Institute of Cancer Research and Treatment of Candiolo
• Lithuania
  • Vilnius, Lithuania, 08660
    • Active, not recruiting
    • National Cancer Institute
  • Vilnius, Lithuania, 08661
    • Active, not recruiting
    • Vilnius University Hospital Santaros Klinikos
• New Zealand
  • Auckland, New Zealand, 1023
    • Active, not recruiting
    • Auckland District Health Board, Auckland City Hospital
• Norway
  • Oslo, Norway, 0372
    • Active, not recruiting
    • Oslo University Hospital, Rikshospitalet (The National Hospital)
• Poland
  • Białystok, Poland, 15-027
    • Active, not recruiting
    • Maria Sklodowska-Curie Bialystok Oncology Center
  • Białystok, Poland, 15-276
    • Active, not recruiting
    • University Teaching Hospital in Bialystok
  • Gdańsk, Poland, 80-214
    • Active, not recruiting
    • University Clinical Center, Clinic of Gynecology
  • Gdynia, Poland, 81-519
    • Active, not recruiting
    • Provincial Hospitals in Gdynia Sp. z o.o. (LLC)
  • Poznań, Poland, 60-569
    • Active, not recruiting
    • Heliodor Swiecicki Clinical Hospital at the Karol Marcinkowski Medical University in Poznań
• Spain
  • Badalona, Spain, 08916
    • Recruiting
    • University Hospital Germans Trias i Pujol
    • Contact: Margarita Romeo Marin, MD
    • Principal Investigator: Margarita Romeo Marin, MD
  • Barcelona, Spain, 08035
    • Active, not recruiting
    • University Hospital Vall d'Hebron
  • Barcelona, Spain, 08036
    • Active, not recruiting
    • Hospital Clinic of Barcelona
  • El Palmar, Spain, 30120
    • Active, not recruiting
    • University Clinical Hospital Virgen de la Arrixaca
  • Jaen, Spain, 23007
    • Recruiting
    • Jaen Hospital Complex
    • Contact: Fernando Galvez, MD
    • Principal Investigator: Fernando Galvez, MD
  • Madrid, Spain, 28040
    • Recruiting
    • University Hospital Foundation Jimenez Diaz
    • Contact: Victor Moreno Garcia, MD
  • Madrid, Spain, 28027
    • Recruiting
    • Clinica Univ di Navarra
    • Contact: Martin Gonzalez, MD
    • Principal Investigator: Martin Gonzalez, MD
  • Madrid, Spain, 28027
    • Active, not recruiting
    • Navarra university clinic
  • Madrid, Spain, 28040
    • Recruiting
    • University Hospital Clinical San Carlos
    • Contact: Aranzazu Manzano Fernandez, MD
    • Principal Investigator: Aranzazu Manzano Fernandez, MD
  • Madrid, Spain, 28046
    • Active, not recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28046
    • Active, not recruiting
    • La Paz University Hospital
  • Madrid, Spain, 28050
    • Recruiting
    • Clara Campal Comprehensive Cancer Center
    • Contact: Emiliano Calvo, MD
    • Principal Investigator: Emiliano Calvo, MD
  • Sevilla, Spain, 41013
    • Recruiting
    • University Hospital Virgen del Rocio (HUVR)
    • Contact: Purificacion Estevez, MD
    • Principal Investigator: Purificacion Estevez, MD
  • Valencia, Spain, 46010
    • Recruiting
    • University Clinical Hospital of Valencia
    • Contact: José Alejandro Pérez Fidalgo, MD
    • Principal Investigator: Jose Alejandro Perez Fidalgo, MD
• Sweden
  • Lund, Sweden, 22100
    • Active, not recruiting
    • Lund University, Department of Oncology
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Active, not recruiting
    • Addenbrooke's Hospital
  • Glasgow, United Kingdom, G12 0YN
    • Active, not recruiting
    • Beatson West of Scotland Cancer Center
  • London, United Kingdom, NW1 2PG
    • Active, not recruiting
    • University College London Hospitals NHS Foundation Trust
  • London, United Kingdom, SE1 9RT
    • Active, not recruiting
    • Guy's Hospital
  • London, United Kingdom, SM2 5PT
    • Active, not recruiting
    • Royal Marsden Hospital - London, Gynae Trials Unit
  • Manchester, United Kingdom, M20 4BX
    • Active, not recruiting
    • The Christie NHS Foundation Trust
  • Northwood, United Kingdom, HA6 2RN
    • Active, not recruiting
    • Mount Vernon Hospital, Cancer Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Active, not recruiting
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35233
      • Active, not recruiting
      • UAB Women & Infants Center
  • Arizona
    • Phoenix, Arizona, United States, 85712
      • Active, not recruiting
      • Arizona Oncology Associates, PC - HAL
    • Tucson, Arizona, United States, 85712
      • Active, not recruiting
      • Arizona Oncology Associates
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Active, not recruiting
      • Highlands Oncology Group
  • California
    • Los Angeles, California, United States, 90048
      • Active, not recruiting
      • Cedars Sinai Medical Center
    • Oakland, California, United States, 94611
      • Active, not recruiting
      • Kaiser Permanente Medical Center - Oakland
    • Orange, California, United States, 92868
      • Recruiting
      • University of California - Irvine
      • Contact: Jill Tseng, MD
      • Principal Investigator: Jill Tseng, MD
    • Roseville, California, United States, 95678
      • Active, not recruiting
      • Kaiser Permanente Medical Center - Roseville
    • Sacramento, California, United States, 95814
      • Active, not recruiting
      • Kaiser Permanente Medical Center - Sacramento
    • San Francisco, California, United States, 94112
      • Active, not recruiting
      • Kaiser Permanente Medical Center - South San Francisco
    • San Francisco, California, United States, 94115
      • Active, not recruiting
      • Kaiser Permanente Medical Center - San Francisco
    • San Jose, California, United States, 95116
      • Active, not recruiting
      • Kaiser Permanente Medical Center - San Jose
    • San Leandro, California, United States, 94115
      • Active, not recruiting
      • Kaiser Permanente Medical Center - San Leandro
    • Santa Barbara, California, United States, 93105
      • Active, not recruiting
      • Sansum Clinic
    • Santa Clara, California, United States, 95051
      • Active, not recruiting
      • Kaiser Permanente Medical Center - Santa Clara
    • Vallejo, California, United States, 94503
      • Active, not recruiting
      • Kaiser Permanente Medical Center - Vallejo
    • Walnut Creek, California, United States, 94595
      • Active, not recruiting
      • Kaiser Permanente Medical Center - Walnut Creek
  • Colorado
    • Boulder, Colorado, United States, 80309
      • Active, not recruiting
      • University of Colorado
    • Lone Tree, Colorado, United States, 80124
      • Withdrawn
      • Rocky Mountain Cancer Centers, LLP
  • Florida
    • Fort Lauderdale, Florida, United States, 20910
      • Active, not recruiting
      • Holy Cross Hospital
    • Gainesville, Florida, United States, 32611
      • Withdrawn
      • University of Florida
    • Jacksonville, Florida, United States, 32224
      • Withdrawn
      • Mayo Clinic - Jacksonville
    • Miami, Florida, United States, 33176
      • Active, not recruiting
      • Miami Cancer Institute
    • Miami, Florida, United States, 33136
      • Active, not recruiting
      • University of Miami - Miller School of Medicine
    • Tampa, Florida, United States, 33612
      • Withdrawn
      • H. Lee Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Active, not recruiting
      • Emory University
    • Augusta, Georgia, United States, 30912
      • Active, not recruiting
      • Georgia Cancer Center at Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Active, not recruiting
      • University of Chicago
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Active, not recruiting
      • Maryland Oncology and Hematology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Active, not recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Active, not recruiting
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Active, not recruiting
      • Dana Farber Cancer Insititute
    • Burlington, Massachusetts, United States, 01805
      • Active, not recruiting
      • Lahey Clinic
    • Springfield, Massachusetts, United States, 01199
      • Active, not recruiting
      • Baystate Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Active, not recruiting
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
      • Contact: Kelly Schneider; Phone Number: 313-576-9749
      • Principal Investigator: Ira Winer, MD
    • Farmington Hills, Michigan, United States, 48334
      • Withdrawn
      • QUEST Research Institute
    • Grand Rapids, Michigan, United States, 49546
      • Active, not recruiting
      • START - Midwest
    • Grand Rapids, Michigan, United States, 49546
      • Active, not recruiting
      • START-Midwest
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Withdrawn
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Active, not recruiting
      • Mayo Clinic - Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Active, not recruiting
      • Washington University
  • Montana
    • Billings, Montana, United States, 59101
      • Active, not recruiting
      • Billings Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Active, not recruiting
      • Nebraska Methodist Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Active, not recruiting
      • MD Anderson Cancer Center at Cooper - Camden
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Recruiting
      • Southwest Women's Oncology- Optimum Clinical Research Group
      • Contact: Karen Finkelstein, MD
      • Principal Investigator: Karen Finkelstein, MD
  • New York
    • Albany, New York, United States, 12208
      • Active, not recruiting
      • Women's Cancer Care Associates, LLC
    • New York, New York, United States, 10029
      • Active, not recruiting
      • Mount Sinai Hospital
    • New York, New York, United States, 10016
      • Active, not recruiting
      • NYU Langone Health
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Active, not recruiting
      • Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28204
      • Active, not recruiting
      • Novant Health Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Active, not recruiting
      • University of Cincinnati Medical Center
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Wexner Medical Center
      • Contact: John Hays, MD
      • Principal Investigator: John Hays, MD
    • Kettering, Ohio, United States, 45429
      • Active, not recruiting
      • Kattering Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Active, not recruiting
      • Stephenson Cancer Centre-University of Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Active, not recruiting
      • Oklahoma Cancer Specialists and Research Institute
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Withdrawn
      • Willamette Valley Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Active, not recruiting
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Perelman Center for Advanced Medicine
      • Contact: Lainie Martin
    • Pittsburgh, Pennsylvania, United States, 15222
      • Active, not recruiting
      • Allegheny Health Network
    • Pittsburgh, Pennsylvania, United States, 15232
      • Active, not recruiting
      • UPMC Cancer Pavillion
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Active, not recruiting
      • Women & Infants Hospital of Rhode Island
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Active, not recruiting
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29604
      • Active, not recruiting
      • Institute of Transnational Oncology-Greenville Hospital System University Medical Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Active, not recruiting
      • Avera Cancer Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37996
      • Active, not recruiting
      • University of Tennessee
    • Nashville, Tennessee, United States, 37203
      • Active, not recruiting
      • Sarah Cannon Research Institute
  • Texas
    • Austin, Texas, United States, 78705
      • Withdrawn
      • Texas Oncology, Austin
    • Austin, Texas, United States, 78731
      • Active, not recruiting
      • Texas Oncology-Austin
    • Bedford, Texas, United States, 76022
      • Active, not recruiting
      • Texas Oncology- Bedford
    • Dallas, Texas, United States, 75201
      • Recruiting
      • Mary Crowley Cancer Research Center
      • Principal Investigator: Minal Barve, MD
      • Contact: Riser; Phone Number: 972-566-3066
    • Dallas, Texas, United States, 75246
      • Active, not recruiting
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75246
      • Active, not recruiting
      • Texas Oncology Baylor Charles A. Sammons Cancer Center
    • Fort Worth, Texas, United States, 76104
      • Active, not recruiting
      • Texas Oncology, Fort Worth
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Texas Oncology-Fort Worth Cancer Center
      • Contact: Noelle Cloven
    • Harlingen, Texas, United States, 78550
      • Active, not recruiting
      • Texas Oncology P.A. - Harlingen
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Oncology, Houston
      • Principal Investigator: Donald Richards, MD
      • Contact: Donald Richards, MD
    • Irving, Texas, United States, 75063
      • Active, not recruiting
      • US Oncology Research/Investigational Product Center
    • San Antonio, Texas, United States, 78229
      • Active, not recruiting
      • South Texas Accelerated Research Therapeutics (START)
    • San Antonio, Texas, United States, 78240
      • Withdrawn
      • NEXT Oncology
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Active, not recruiting
      • University of Utah Huntsman Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Active, not recruiting
      • University of Virginia- Emily Couric Clinical Cancer Center
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialist
      • Contact: Alex Spira, MD
    • Richmond, Virginia, United States, 23291
      • Recruiting
      • VCU Massey Cancer Center
      • Contact: Leslie Randall
    • Richmond, Virginia, United States, 23298
      • Active, not recruiting
      • Virginia Commonwealth University Massey Cancer Center
    • Roanoke, Virginia, United States, 24014
      • Active, not recruiting
      • BlueRidge Cancer Care Physicians
    • Salem, Virginia, United States, 24153
      • Active, not recruiting
      • Oncology & Hematology Associates of Southwest Virginia, Inc. - Salem
  • Washington
    • Seattle, Washington, United States, 98195
      • Active, not recruiting
      • University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, 53226
      • Active, not recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

General Inclusion Criteria (for Dose Escalation, Expansion, and UPLIFT):

• ECOG performance status 0 or 1
• Measurable disease as per RECIST, version 1.1
• Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy).
• Cardiac left ventricular ejection fraction (LVEF) ≥50% or ≥ the institution's lower limit of normal by either Echo or MUGA scan

• Adequate organ function as defined by the following criteria:

  1. Absolute neutrophil count (ANC) ≥1500 cells/mm3
  2. Platelet count ≥100,000/mm3
  3. Hemoglobin ≥9 g/dL
  4. In patients not on anticoagulation therapy: INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all within 1.2 times the institution's upper limit of normal (ULN). Patients on anticoagulation therapy are allowed if their relevant laboratory values are within the therapeutic window.
  5. Estimated glomerular filtration rate (GFR) ≥45 mL/min
  6. Total bilirubin ≤ULN
  7. g. Patients with asymptomatic elevations in unconjugated bilirubin due to Gilbert syndrome or stable chronic hemolytic anemia (e.g., hereditary spherocytosis, sickle cell disease, thalassemia intermedia) may be eligible after discussion with the Sponsor Medical Monitor.
• Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤1.5 times the institutional ULN.
• Albumin ≥3.0 g/dL
• Able to provide informed consent.

General Exclusion Criteria (for Dose Escalation, Expansion, and UPLIFT) :

• Major surgery within 28 days of starting study treatment, systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment, or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity.
• Patients with untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
• Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
• Prior history of liver disease such as liver cirrhosis, hepatic fibrosis
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations.
• Current use of either constant or intermittent supplementary oxygen therapy.
• History of suspected pneumonitis or interstitial lung disease.
• Pregnant or nursing women.
• History of other malignancy within the last 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
• Active corneal disease, or history of corneal disease within 12 months prior to enrollment
• Use of strong CYP450 3A inhibitors or inducers that cannot be discontinued while receiving study treatment
• Oxygen saturation on room air <93%

Ovarian Cancer Inclusion Criteria for UPLIFT:

• Histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer, that is metastatic or recurrent.

• Platinum-resistant disease

  1. Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response [complete response/remission (CR) or partial response/remission (PR)], and then progressed between 3 months and ≤ 6 months after the date of the last dose of platinum
  2. Patients who have received 2 to 4 lines of prior therapy must have received at least 4 cycles of platinum and then progressed within 6 months after the date of the last dose of platinum

• One to 4 prior lines of systemic therapy for ovarian cancer

  a. Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy

• Patients must be willing to provide an archival tumor tissue block or slides or if not available, undergo procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure

Ovarian Cancer Exclusion Criteria for UPLIFT:

• Low-grade, clear cell, endometrioid, mucinous, carcinosarcoma, germ-cell, mixed histology, or stromal tumors
• Prior treatment with mirvetuximab soravtansine or another ADC containing an antitubulin payload
• Primary platinum-resistant disease, defined by a lack of response or by progression within 3 months after completing front-line, platinum-containing therapy.
• Participation in DES or EXP segments of this study

Ovarian Cancer Inclusion Criteria for QTc sub-study:

Note: patients must meet all UPLIFT cohort inclusion criteria in order to participate in the QTc sub-study

• Study patient has agreed to remain in the clinic for the additional QTc related study activities on the Day 1 of Cycle 1 and Cycle 3.

Ovarian Cancer Exclusion Criteria for QTc sub-study:

• Use of strong CYP450 3A inducers.
• Uncontrolled cardiac arrhythmias, for example, atrial fibrillation with a ventricular response at rest > 100 beats per minute. left bundle branch block (LBBB)
• Known abnormality of any cardiac valve (either stenosis or regurgitation) that is greater than moderate in severity.
• Subjects not in sinus rhythm at screening with HR >45- <100
• Any ECG abnormality that can interfere with the measurement of the QT interval

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; XMT-1536 (upifitamab rilsodotin) treatment is administered in groups of patients who will receive doses that increase over time. This cohort is closed to enrollment.	Drug: upifitamab rilsodotin; XMT-1536 will be administered once every 28 days until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study. For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536; Other Names: XMT-1536; UpRi
Experimental: Dose Expansion - Ovarian Cancer; Once the maximum tolerated dose or recommended Phase 2 dose is achieved in dose escalation, new groups of patients will receive XMT-1536 (upifitamab rilsodotin) at this fixed-dose. This cohort is closed to enrollment.	Drug: upifitamab rilsodotin; XMT-1536 will be administered once every 28 days until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study. For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536; Other Names: XMT-1536; UpRi
Experimental: Dose Expansion - NSCLC adenocarcinoma; Once the maximum tolerated dose or recommended Phase 2 dose is achieved in dose escalation, new groups of patients will receive XMT-1536 (upifitamab rilsodotin) at this fixed-dose. This cohort is closed to enrollment.	Drug: upifitamab rilsodotin; XMT-1536 will be administered once every 28 days until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study. For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536; Other Names: XMT-1536; UpRi
Experimental: Pivotal Cohort (UPLIFT); Patients with platinum-resistant ovarian cancer will receive XMT-1536 (upifitamab rilsodotin) to further confirm the efficacy	Drug: upifitamab rilsodotin; XMT-1536 will be administered once every 28 days until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study. For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536; Other Names: XMT-1536; UpRi
Experimental: QTc Sub-Study; For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536.	Drug: upifitamab rilsodotin; XMT-1536 will be administered once every 28 days until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study. For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536; Other Names: XMT-1536; UpRi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DES: Maximum tolerated dose or recommended Phase 2 dose	Evaluate adverse events and concomitant medication use after XMT-1536 (upifitamab rilsodotin) doses	Up to 36 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met
DES and EXP: Safety and Tolerability	Evaluate incidence and severity of adverse events	First dose up until 30 days after study termination
EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin)	Monitor tumor size	Every 6 weeks for up to 36 weeks
UPLIFT: Investigator-assessed objective response rate (ORR) of XMT-1536 (upifitamab rilsodotin) in the ITT-Higher NaPi2b population	Confirmed ORR is defined as the proportion of patients who have achieved a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 after the initiation of study treatment.	Every 8 weeks until disease progression or up to 24 months
QTc Sub-study: Evaluation of the concentration response analysis of XMT-1536 versus the change in QTcF values	"The concentration-QTcf change from baseline deltaQTcF analysis and analysis of central tendency for deltaQTcF	60 minutes prior to first dose, up to 26 hours after Cycle 3 dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DES and EXP: Time of maximum observed concentration of XMT-1536 (upifitamab rilsodotin)	Determine the pharmacokinetics of XMT-1536 (upifitamab rilsodotin)	Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Maximum concentration of XMT-1536 (upifitamab rilsodotin)	Determine the pharmacokinetics of XMT-1536 (upifitamab rilsodotin)	Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Area under the concentration curve of the last measurable concentration of XMT-1536 (upifitamab rilsodotin)	Determine the pharmacokinetics of XMT-1536 (upifitamab rilsodotin)	Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin)	Monitor tumor size	Every 6 weeks for up to 36 weeks
DES and EXP: Anti-drug antibody and neutralizing antibody	Analyze blood for antibodies to XMT-1536 (upifitamab rilsodotin) and neutralizing antibodies	Every 6 weeks for up to 36 weeks
UPLIFT: Confirmed Investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) regardless of NaPi2b expression	Assess the confirmed investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) regardless of NaPi2b expression	Every 8 weeks until disease progression or up to 24 months
UPLIFT: Confirmed objective response rate by independent radiology review (IRR) for patients with high NaPi2b and overall	Assess the confirmed objective response rate by IRR for patients with high NaPi2b (TPS >/=75) and overall	Every 8 weeks until disease progression or up to 24 months
UPLIFT: Duration of objective response (DOR)	Assess the duration of objective response (DOR) in patients who achieve a response	4 weeks after first response and every 8 weeks until disease progression or up to 24 months
UPLIFT: Incidence and severity of adverse events	Evaluate incidence and severity of adverse events	First dose up until 60 days after study termination
QTc Sub-Study: Evaluation of the effect of XMT-1536 on QTcF in patients with platinum-resistant HGSOC by timepoint analysis	Con.-QTc evaluation	60 minutes prior to first dose, up to 26 hours after Cycle 3 dose
QTc Sub-Study: Evaluation of the effect of XMT-1536 on the PR-interval (PR), QRS duration (QRS), Heart Rate (HR), and ECG morphology	Con.-QTc evaluation	60 minutes prior to first dose, up to 26 hours after Cycle 3 dose

Collaborators and Investigators

• Sponsor: Mersana Therapeutics
• Collaborators: IQVIA Biotech; PSI CRO
• Investigators: Study Director: Leslie DeMars, MD, Mersana Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2017
• Primary Completion (Anticipated): April 30, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: October 17, 2017
• First Submitted That Met QC Criteria: October 19, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): January 25, 2023
• Last Update Submitted That Met QC Criteria: January 23, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: XMT-1536-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No