A Study of XMT-1660 in Participants With Solid Tumors

Phase 1

Recruiting

• Conditions: Triple Negative Breast Cancer; Endometrial Cancer; Fallopian Tube Cancer; Breast Cancer; Ovarian Cancer; Adenoid Cystic Carcinoma; Primary Peritoneal Cavity Cancer
• Interventions: Drug: XMT-1660

• Registration Number: NCT05377996
• Lead Sponsor: Mersana Therapeutics

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.

Study Timeline

• Study First Submitted: 2022-05-02
• Study First Submitted QC: 2022-05-11
• Study First Posted: 2022-05-17
• Study Start: 2022-08-15
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-19
• Last Update Posted: 2024-03-20
• Primary Completion: 2026-12
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 319

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
XMT-1660	XMT-1660	Single arm XMT-1660 alone (monotherapy)

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (Dose Escalation and Dose Expansion)	3 years	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
Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with XMT-1660 during the first cycle of treatment (Dose Escalation)	17 months	Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of XMT-1660
Objective Response Rate (ORR) (Dose Expansion)	approximately 3 years	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

Secondary Outcome Measures

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

Trial Locations

Locations (18)

UC Irvine Health-Chao Family Comprehensive Cancer Center; 🇺🇸 Orange, California, United States

UCLA; 🇺🇸 Santa Monica, California, United States

Florida Cancer Specialists; 🇺🇸 Sarasota, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Winship Cancer Institute, Emory University; 🇺🇸 Atlanta, Georgia, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Henry Ford Health Hospital; 🇺🇸 Detroit, Michigan, United States

New York University Langone Health; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Stephenson Cancer Center Oklahoma University Health; 🇺🇸 Oklahoma City, Oklahoma, United States

Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States

Tennessee Oncology, PLLC; 🇺🇸 Nashville, Tennessee, United States

Texas Oncology, P.A.; 🇺🇸 Dallas, Texas, United States

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

NEXT Oncology Virginia; 🇺🇸 Fairfax, Virginia, United States

Summit Cancer Centers; 🇺🇸 Spokane, Washington, United States