A Study of XMT-2056 in Advanced/Recurrent Solid Tumors That Express HER2

A Phase 1, First-in-Human, Dose Escalation and Expansion, Multicenter Study of XMT-2056 in Participants With Advanced/Recurrent Solid Tumors That Express HER2

A Study of XMT-2056 in advanced/recurrent solid tumors that express HER2.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Breast Cancer; HER2-positive Gastric Cancer; HER2-positive Non-Small Cell Lung Cancer; HER2-positive Colorectal Cancer; HER2-positive Tumors; HER2 Low Breast Cancer
• Intervention / Treatment: Drug: XMT-2056

Detailed Description

The first-in-human (FIH) study of XMT-2056 is a Phase 1, open-label study of XMT-2056 in previously treated patients with advanced/recurrent solid tumors expressing HER2. The XMT-2056 monotherapy trial will consist of dose escalation (DES) and expansion (EXP) parts.

DES will be the dose-finding portion of the study to assess the safety and tolerability of XMT-2056 and determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D). The RP2D will be determined based on the totality of the clinical data, including safety and preliminary anti-tumor effect, PK, and relevant biomarker data.

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: June Buchanan; Phone Number: 617-844-8613; Email: medicalinformation@mersana.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles
      • Contact: Nicholas McAndrew, MD
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of South California
      • Contact: Anthony El-Khoueiry, MD
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University Medical Center
      • Contact: Christopher Chen, MD
  • Florida
    • Celebration, Florida, United States, 34747
      • Recruiting
      • AdventHealth Celebration
      • Contact: Guru Sonpavde, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory Healthcare, Emory Clinic
      • Contact: Manali Bhave, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Samuel Klempner, MD
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
      • Contact: Jailan Elayoubi, MD
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center
      • Contact: Martin Gutierrez, MD
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Ezra Rosen, MD
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Principal Investigator: Deborah Doroshow
      • Contact: Deborah Doroshow, MD
    • New York, New York, United States, 10016
      • Recruiting
      • New York University Medical Oncology Associates
      • Contact: Kristen Spencer, MD
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Recruiting
      • The Ohio State University Comprehensive Cancer Center
      • Contact: Arya Roy, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology, Pllc
      • Contact: Erika P Hamilton, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Ecaterina Dumbrava, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has recurrent or metastatic solid tumors with HER2 expression and has disease progression after treatment, is intolerant to treatment, or is contraindicated with available anti-cancer therapies known to confer benefit, based on investigator's judgement. Note: Participants must have HER2 positivity per the results of their most recent tumor tissue testing, defined as IHC 3+ or IHC 2+ in combination with in situ hybridization (ISH)+. Participants with ERBB2-activating mutations or ERBB2 gene amplification in the absence of HER2 positivity are considered ineligible.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Participant must have measurable disease as defined by RECIST version 1.1.
• Participant has fresh tumor biopsy tissue available for submission to central laboratory. If obtaining fresh tumor tissue is medically contraindicated, archival tumor tissue can be submitted following written approval of the request by the study Medical Monitor. Samples must be obtained after the participant's most recent HER2-targeting therapy unless determined to be medically contraindicated after discussion with the medical monitor.

Exclusion Criteria:

• • Participant is receiving immunosuppressive doses of systemic medications, (doses >10 mg/day prednisone or equivalent) that cannot be discontinued for at least 2 weeks before the first dose and during study drug treatment administration. Note: physiologic hormone replacement therapy is an exception.
• Participant has received prior treatment targeting STING pathway.
• Diagnosis of additional malignancy that required active treatment (including surgery, systemic therapy, and radiation) within the last 2 years, expect for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the breast or the cervix. Participants with an additional malignancy that has a low risk for recurrence may be eligible after discussion with the study Medical Monitor.

• Participants have 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 prednisone daily (or equivalent).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XMT-2056; XMT-2056 alone (monotherapy)	Drug: XMT-2056; XMT-2056 will be administered through a vein in your arm or port catheter (intravenously)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (Dose Escalation and Dose Expansion)	Assess the safety and tolerability of XMT-2056 by determining the number of patients with adverse events from date of first dose to 30 days post last dose.	3 years
Frequency of dose-limiting toxicities (DLTs) associated with XMT-2056 during the first cycle of treatment (Dose Escalation)	Determine the maximum tolerated dose (MTD) of XMT-2056	15 months
Objective Response Rate (ORR) (Dose Expansion)	The percentage of patients with a best overall response of confirmed complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of maximum observed plasma concentration of XMT-2056 (Tmax) (Dose Escalation and Dose Expansion)	Assess the pharmacokinetics of XMT-2056	3 years
Maximum observed plasma concentration of XMT-2056 (Cmax) (Dose Escalation and Dose Expansion)	Assess the pharmacokinetics of XMT-2056	3 years
Area under the concentration-time curve of XMT-2056 (AUC) (Dose Escalation and Dose Expansion)	Assess the pharmacokinetics of XMT-2056	3 years
Systemic clearance of XMT-2056 (Dose Escalation and Dose Expansion)	Assess the pharmacokinetics of XmT-2056 by measuring the rate at which the drug is eliminated from the body	3 years
Apparent terminal elimination of half-life of XMT-2056 (Dose Escalation and Dose Expansion)	Assess the pharmacokinetics of XMT-2056	3 years
Volume of Distribution (Dose Escalation and Dose Expansion)	Assess the pharmacokinetics of XMT-2056	3 years
Trough concentration of XMT-2056 (Ctrough) (Dose Escalation and Dose Expansion)	Assess the pharmacokinetics of XMT-2056 by measuring the lowest concentration of drug before dosing	3 years
Objective Response Rate (ORR) (Dose Escalation)	The percentage of patients with a best overall response of confirmed complete or partial response as assessed by the investigator per Resist Evaluation Criteria in Solid Tumors (RECIST) version 1.1	3 years
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 confirmed complete or partial response.	3 years
Disease control rate (DCR) (Dose Escalation and Dose Expansion)	The percentage of patients who achieve a complete response, partial response or stable disease as the result of study treatment	3 years
Serum samples for analysis of XMT-2056 antidrug and neutralizing antibodies (ADA/nAb) (Dose Escalation and Dose Expansion)	Assess the development of antidrug antibodies (ADA) and neutralizing antibodies (nAB) to XMT-2056	3 years

Collaborators and Investigators

• Sponsor: Mersana Therapeutics
• Investigators: Study Director: Brad Sumrow, MD, Mersana Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 23, 2022
• First Posted (Actual): August 24, 2022

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: MER-XMT-2056-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No