Clinical trial NCT05377996: A Study of XMT-1660 in Participants With Solid Tumors
Official title: A Phase 1, First-in-human, Dose Escalation and Expansion, Multicenter Study of XMT-1660 in Participants With Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Triple Negative Breast Cancer
Breast Cancer
Endometrial Cancer
Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cavity Cancer
Adenoid Cystic Carcinoma
Lead sponsor: Mersana Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-05-17
Enrollment: 319
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with XMT-1660 during the first cycle of treatment (Dose Escalation)
timeFrame: 17 months
measure: Incidence of adverse events (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Objective Response Rate (ORR) (Dose Expansion)
timeFrame: approximately 3 years
Secondary outcomes:
measure: Objective Response Rate (ORR) (Dose Escalation)
timeFrame: Up to approximately 3 years
measure: Duration of response (DOR) (Dose Escalation and Dose Expansion)
timeFrame: Up to approximately 3 years
measure: Time of maximum observed plasma concentration of XMT-1660 (Tmax) (Dose Expansion)
timeFrame: 3 years
measure: Maximum observed plasma concentration of XMT-1660 (Cmax) (Dose Expansion)
timeFrame: 3 years
measure: Area under the concentration-time curve of XMT-1660 (AUC) (Dose Expansion)
timeFrame: 3 years
measure: Systemic clearance of XMT-1660 (Dose Expansion)
timeFrame: 3 years
measure: Apparent terminal elimination half-life of XMT-1660 (Dose Expansion)
timeFrame: 3 years
measure: Volume of Distribution (Dose Expansion)
timeFrame: 3 years
measure: Trough concentration of XMT-1660 (Ctrough) (Dose Expansion)
timeFrame: 3 years
measure: Assess antidrug antibodies (ADA) and neutralizing antibodies (nAB) (Dose Escalation and Dose Expansion)
timeFrame: 3 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine Health-Chao Family Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health Hospital
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: New York University Langone Health
state: New York
city: New York
country: United States
facility: ICHAN School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center Oklahoma University Health
state: Oklahoma
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: NEXT Oncology Virginia
state: Virginia
city: Spokane
country: United States
facility: Summit Cancer Centers
state: Washington
Study officials:
affiliation: Mersana Therapeutics
name: Robert Burger, MD
role: STUDY_DIRECTOR
References: