Clinical trial NCT05514717: A Study of XMT-2056 in Advanced/Recurrent Solid Tumors That Express HER2
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: Mersana Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-08-24
Enrollment: 162
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-2056 in advanced/recurrent solid tumors that express HER2.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Frequency of dose-limiting toxicities (DLTs) associated with XMT-2056 during the first cycle of treatment (Dose Escalation)
timeFrame: 15 months
measure: Incidence of adverse events (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Objective Response Rate (ORR) (Dose Expansion)
timeFrame: 3 years
Secondary outcomes:
measure: Objective Response Rate (ORR) (Dose Escalation)
timeFrame: 3 years
measure: Duration of response (DOR) (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Disease control rate (DCR) (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Time of maximum observed plasma concentration of XMT-2056 (Tmax) (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Maximum observed plasma concentration of XMT-2056 (Cmax) (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Area under the concentration-time curve of XMT-2056 (AUC) (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Systemic clearance of XMT-2056 (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Apparent terminal elimination of half-life of XMT-2056 (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Volume of Distribution (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Trough concentration of XMT-2056 (Ctrough) (Dose Escalation and Dose Expansion)
timeFrame: 3 years
measure: Serum samples for analysis of XMT-2056 antidrug and neutralizing antibodies (ADA/nAb) (Dose Escalation and Dose Expansion)
timeFrame: 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of South California
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: New York University Medical Oncology Associates
state: New York
city: New York
country: United States
facility: Icahn 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: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Mersana Therapeutics
name: Brad Sumrow, MD
role: STUDY_DIRECTOR
References: