A Phase 1, First-in-human, Dose Escalation and Expansion, Multicenter Study of XMT-1660 in Participants With Solid Tumors
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
Study locations (26)
Mayo Clinic Comprehensive Cancer Center
Phoenix, Arizona, 85054
UC Irvine Health-Chao Family Comprehensive Cancer Center
Orange, California, 92868
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
UCLA David Geffen School of Medicine, Division of Hematology/Oncology
Santa Monica, California, 90404
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
Florida Cancer Specialists
Sarasota, Florida, 34232
Moffitt Cancer Center
Tampa, Florida, 33612
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
Northwestern University
Chicago, Illinois, 60611
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Henry Ford Health Hospital
Detroit, Michigan, 48202
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
New York University Langone Health
New York, New York, 10016
ICHAN School of Medicine at Mount Sinai
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Stephenson Cancer Center Oklahoma University Health
Oklahoma City, Oklahoma, 73104
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
Sarah Cannon Research Institute (SCRI)
Nashville, Tennessee, 37203
Texas Oncology, P.A.
Dallas, Texas, 75251
MD Anderson
Houston, Texas, 77030
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
NEXT Oncology Virginia
Fairfax, Virginia, 22031
Fred Hutchinson Cancer Center
Seattle, Washington, 09109
Summit Cancer Centers
Spokane, Washington, 99208
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)