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RecruitingInterventionalPhase 1

A Phase 1, First-in-human, Dose Escalation and Expansion, Multicenter Study of XMT-1660 in Participants With Solid Tumors

NCT ID: NCT05377996Sponsor: Mersana TherapeuticsLast updated: 2026-04-14

Summary

A Study of XMT-1660 in Solid Tumors

Detailed description

This first-in-human (FIH) study will test the safety and side effects of a drug called XMT-1660. A side effect is anything a drug does to the body besides treating the disease. Participants in the study will have cancer that has come back after a period of time during which the cancer could not be detected (recurrent), spread in the body near where it started (advanced) or spread through the body (metastatic). The study will have two parts. The first part called Dose Escalation will find out how much XMT-1660 should be given to participants. The second part called Dose Expansion will use the dose found in the first part to find out how safe XMT-1660 is and if it works to treat solid tumor cancers.

Arms & interventions

  • DrugXMT-1660

    XMT-1660 will be administered through a vein in your arm or port catheter (intravenously)

Outcome measures

Primary

  • Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with XMT-1660 during the first cycle of treatment (Dose Escalation)

    Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of XMT-1660

    Time frame: 17 months

  • Incidence of adverse events (Dose Escalation and Dose Expansion)

    Assess the safety and tolerability of XMT-1660 by determining the number of patients with adverse events from date of first dose to 30 days post last dose

    Time frame: 3 years

  • Objective Response Rate (ORR) (Dose Expansion)

    The percentage of patients with a best overall response of complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Time frame: approximately 3 years

Secondary

  • Objective Response Rate (ORR) (Dose Escalation)

    Time frame: Up to approximately 3 years

  • Duration of response (DOR) (Dose Escalation and Dose Expansion)

    Time frame: Up to approximately 3 years

  • Time of maximum observed plasma concentration of XMT-1660 (Tmax) (Dose Expansion)

    Time frame: 3 years

  • Maximum observed plasma concentration of XMT-1660 (Cmax) (Dose Expansion)

    Time frame: 3 years

  • Area under the concentration-time curve of XMT-1660 (AUC) (Dose Expansion)

    Time frame: 3 years

  • Systemic clearance of XMT-1660 (Dose Expansion)

    Time frame: 3 years

  • Apparent terminal elimination half-life of XMT-1660 (Dose Expansion)

    Time frame: 3 years

  • Volume of Distribution (Dose Expansion)

    Time frame: 3 years

  • Trough concentration of XMT-1660 (Ctrough) (Dose Expansion)

    Time frame: 3 years

  • Assess antidrug antibodies (ADA) and neutralizing antibodies (nAB) (Dose Escalation and Dose Expansion)

    Time frame: 3 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Recurrent or advanced solid tumor and has disease * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Participants in DES must have at least one non-target lesion as defined by RECIST version 1.1. Participants in Backfill Cohorts and EXP must have at least one measurable disease (target) lesion as defined by RECIST version 1.1. * Tumor tissue, either archival or from a fresh tumor biopsy, available for testing or be willing to undergo a minimally invasive tumor biopsy to obtain tumor tissue for local testing, if not medically contraindicated, prior to Cycle 1 Day 1 * Brain magnetic resonance imaging (MRI) during the Screening period unless obtained within 30 days prior to Screening (based on standard clinical care), if they meet either of the following criteria: 1. All participants with TNBC 2. Participants with a history of brain metastases or with neurologic symptoms or signs suspicious for brain metastases. Exclusion Criteria: * Prior treatment with an Antibody Drug Conjugate (ADC) containing an auristatin payload. Prior treatment with another ADC containing other payloads is allowed. * Major surgery within 28 days of starting study treatment, systemic anticancer therapy within the time period of 28 days or 5 half-lives of the prior therapy before starting study treatment (14 days or 5 half-lives for small molecule targeted therapy), whichever is less, or palliative radiation therapy to the chest within 3 months of starting study treatment or to other anatomic sites within 14 days of starting study treatment. * Diagnosis of additional malignancy that required active treatment (including surgery, systemic therapy, and radiation) within 2 years prior to screening, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix. * Untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis. * Prior B7-H4 targeted treatment. * History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver diseases. * Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could increase the risk of serious adverse events (SAEs) or interfere with per-protocol evaluations, in the judgment of either the Sponsor or the Investigator. * Clinically significant cardiovascular disease

Study locations (26)

Mayo Clinic Comprehensive Cancer Center

Phoenix, Arizona, 85054

Recruiting
Felipe Batalini, MD · Contact
Felipe Batalini, MD · Principal Investigator

UC Irvine Health-Chao Family Comprehensive Cancer Center

Orange, California, 92868

Recruiting
Ritesh Parajuli · Contact
Ritesh Parajuli · Principal Investigator

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158

Recruiting
Laura Huppert, MD · Contact
Laura Huppert, MD · Principal Investigator

UCLA David Geffen School of Medicine, Division of Hematology/Oncology

Santa Monica, California, 90404

Recruiting
Nicholas McAndrew, MD · Contact
Nicholas McAndrew, MD · Principal Investigator

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224

Recruiting
Pooja Advani, MD · Contact
Pooja Advani, MD · Principal Investigator

Florida Cancer Specialists

Sarasota, Florida, 34232

Recruiting
Judy Wang · Contact
Judy Wang · Principal Investigator

Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting
Hyo Han, MD · Contact
Hyo Han, MD · Principal Investigator

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322

Recruiting
Kevin Kalinsky, MD · Contact

Northwestern University

Chicago, Illinois, 60611

Recruiting
Patricia Robinson, MD · Contact
Patricia Robinson, MD · Principal Investigator

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

Recruiting
Gerburg Wulf, MD · Contact
Gerburg Wulf, MD · Principal Investigator

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting
Antonio Giordano, MD, PhD · Contact

Henry Ford Health Hospital

Detroit, Michigan, 48202

Recruiting
Amy Weise, MD · Contact

Mayo Clinic - Rochester

Rochester, Minnesota, 55905

Recruiting
Roberto Leon-Ferre, MD · Contact
Roberto Leon-Ferre, MD · Principal Investigator

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169

Recruiting
Liawaty Ho, MD · Contact
Liawaty Ho, MD · Principal Investigator

New York University Langone Health

New York, New York, 10016

Recruiting
Nancy Chan, MD · Contact

ICHAN School of Medicine at Mount Sinai

New York, New York, 10029

Not Yet Recruiting
Amy Tiersten · Contact
Amy Tiersten · Principal Investigator

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting
Nour Abuhadra, MD · Contact

Stephenson Cancer Center Oklahoma University Health

Oklahoma City, Oklahoma, 73104

Recruiting
Debra Richardson, MD · Contact
Debra Richardson, MD · Principal Investigator

Avera Cancer Institute

Sioux Falls, South Dakota, 57105

Recruiting
David C. Starks, MD · Contact
David C. Starks, MD · Principal Investigator

Sarah Cannon Research Institute (SCRI)

Nashville, Tennessee, 37203

Recruiting
Erika P Hamilton, MD · Contact

Texas Oncology, P.A.

Dallas, Texas, 75251

Recruiting
Joyce O'Shaughnessy, MD · Principal Investigator

MD Anderson

Houston, Texas, 77030

Recruiting
Funda Meric-Bernstam · Contact
Funda Meric-Bernstam · Principal Investigator

Huntsman Cancer Institute

Salt Lake City, Utah, 84112

Recruiting
Kristen Kelley, MD · Contact
Kristen Kelley, MD · Principal Investigator

NEXT Oncology Virginia

Fairfax, Virginia, 22031

Recruiting
Alex Spira, MD, PhD · Contact

Fred Hutchinson Cancer Center

Seattle, Washington, 09109

Recruiting
Jennifer Specht, MD · Contact

Summit Cancer Centers

Spokane, Washington, 99208

Recruiting
Arvind Chaudhry, MD, PhD · Contact

References

  • Toader D, Fessler SP, Collins SD, Conlon PR, Bollu R, Catcott KC, Chin CN, Dirksen A, Du B, Duvall JR, Higgins S, Kozytska MV, Bellovoda K, Faircloth C, Lee D, Li F, Qin L, Routhier C, Shaw P, Stevenson CA, Wang J, Wongthida P, Ter-Ovanesyan E, Ditty E, Bradley SP, Xu L, Yin M, Yurkovetskiy AV, Mosher R, Damelin M, Lowinger TB. Discovery and Preclinical Characterization of XMT-1660, an Optimized B7-H4-Targeted Antibody-Drug Conjugate for the Treatment of Cancer. Mol Cancer Ther. 2023 Sep 5;22(9):999-1012. doi: 10.1158/1535-7163.MCT-22-0786.(PubMed)