A Study of XMT-1660 in Participants With Solid Tumors

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05377996
• Other study ID #: MER-XMT-1660-1
• Status: Recruiting
• Phase: Phase 1
• Start date: August 15, 2022
• Est. completion date: May 2027

Study information

• Verified date: March 2024
• Source: Mersana Therapeutics
• Contact: Caroline Rogalski
• Phone: 1-617-715-8214
• Email: medicalinformation[@]mersana.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Study of XMT-1660 in Solid Tumors

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 319
• Est. completion date: May 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Recurrent or advanced solid tumor and has disease progression after treatment with available anti-cancer therapies known to confer benefit or is intolerant to treatment.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• At least one measurable lesion(s) 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 Pre- Screening/Screening period unless obtained within 30 days prior to enrollment (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 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.

1. Participants are eligible if CNS metastases are adequately treated, and participants are neurologically stable for at least 2 weeks prior to enrollment.

2. In addition, participants must be either off corticosteroids, or on a stable/decreasing dose of = 10 mg daily prednisone (or equivalent). Anticonvulsants are allowed except for those drugs associated with liver toxicity

3. Participants may be eligible if CNS lesions are asymptomatic, equivocal for metastases or do not require specific therapy in the opinion of the investigator

• 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

Related Conditions & MeSH terms

• Adenoid Cystic Carcinoma
• Breast Cancer
• Breast Neoplasms
• Carcinoma, Adenoid Cystic
• Endometrial Cancer
• Endometrial Neoplasms
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Primary Peritoneal Cavity Cancer
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Henry Ford Health Hospital	Detroit	Michigan
United States	NEXT Oncology Virginia	Fairfax	Virginia
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York University Langone Health	New York	New York
United States	Stephenson Cancer Center Oklahoma University Health	Oklahoma City	Oklahoma
United States	UC Irvine Health-Chao Family Comprehensive Cancer Center	Orange	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCLA	Santa Monica	California
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Summit Cancer Centers	Spokane	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Mersana Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	17 months
Primary	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	3 years
Primary	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	approximately 3 years
Secondary	Objective Response Rate (ORR) (Dose Escalation)	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	Up to approximately 3 years
Secondary	Duration of response (DOR) (Dose Escalation and Dose Expansion)	The time from when response criteria are first met until disease progression or death in participants who achieve a complete or partial response	Up to approximately 3 years
Secondary	Time of maximum observed plasma concentration of XMT-1660 (Tmax) (Dose Expansion)	Assess the pharmacokinetics of XMT-1660	3 years
Secondary	Maximum observed plasma concentration of XMT-1660 (Cmax) (Dose Expansion)	Assess the pharmacokinetics of XMT-1660	3 years
Secondary	Area under the concentration-time curve of XMT-1660 (AUC) (Dose Expansion)	Assess the pharmacokinetics of XMT-1660	3 years
Secondary	Systemic clearance of XMT-1660 (Dose Expansion)	Assess the pharmacokinetics of XMT-1660 by measuring the rate at which the drug is eliminated from the body	3 years
Secondary	Apparent terminal elimination half-life of XMT-1660 (Dose Expansion)	Assess the pharmacokinetics of XMT-1660	3 years
Secondary	Volume of Distribution (Dose Expansion)	Assess the pharmacokinetics of XMT-1660	3 years
Secondary	Trough concentration of XMT-1660 (Ctrough) (Dose Expansion)	Assess the pharmacokinetics of XMT-1660 by measuring the lowest concentration of drug before dosing	3 years
Secondary	Assess antidrug antibodies (ADA) and neutralizing antibodies (nAB) (Dose Escalation and Dose Expansion)	Assess the development of antidrug antibodies (ADA) and neutralizing antibodies (nAb) to XMT-1660	3 years