- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02952729
Study of Antibody Drug Conjugate in Patients With Advanced Breast Cancer Expressing HER2
A Phase 1b, First-in-Human, Dose Escalation and Expansion Study of XMT-1522 in Patients With Advanced Breast Cancer and Other Advanced Tumors Expressing HER2
Study Overview
Status
Intervention / Treatment
Detailed Description
The dose escalation segment of the study utilizes a 3+3 design. Initially, 3 patients will be dosed at each dose level. The first 3-week cycle of treatment constitutes the dose limiting toxicity (DLT) evaluation period. If none of the 3 patients experience a DLT during the evaluation period and the Safety Review Committee agrees this was a reasonably well tolerated dose, 3 patients will be enrolled at the next dose level. However, in the event of 1 DLT, 3 additional patients will be enrolled at the same dose level. Any dose level with 2 or more DLTs will be considered to have exceeded the maximum tolerated dose and subsequent patients will be enrolled at lower dose levels. After the first cycle, patients may continue to receive XMT-1522 until disease progression as long as the drug is well-tolerated and patients continue to derive clinical benefit in the opinion of the Investigator.
After completion of the dose escalation, the expansion segment will enroll the patients with the following kinds of cancer:
- Cohort 1: Advanced breast cancer, HER2 IHC 1+, or HER2 IHC 2+ without HER2 gene amplification
- Cohort 2: Advanced breast cancer, HER2-positive, who have received prior ado-trastuzumab emtansine
- Cohort 3: Advanced gastric cancer, HER2-positive, who have received prior trastuzumab
- Cohort 4: Advanced non-small cell lung cancer, HER2 IHC 2+ or 3+, any HER2 gene amplification or mutation status
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Florida
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Tampa, Florida, United States, 33607
- Moffitt Cancer Center
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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Tennessee
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Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Institute
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Texas
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Dallas, Texas, United States, 75230
- Mary Crowley Cancer Research Center
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San Antonio, Texas, United States, 78229
- South Texas Accelerated Research Therapeutics (START)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Able and willing to give informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Measurable disease via RECIST
- Resolution of all toxic side effects from prior oncology treatments
- Adequate organ function as measured by various blood parameters
- Not pregnant or lactating, willing to prevent pregnancy while on study and for 6 months after the last dose of XMT-1522
- Histologically or cytologically confirmed adenocarcinoma of the breast with unresectable locally advanced disease, or metastatic disease and HER2 IHC 1+ or 2+ OR
- Histologically or cytologically confirmed adenocarcinoma of the breast with unresectable locally advanced disease, or metastatic disease and HER2 IHC 3+ or positive for HER2 gene amplification
- Progressed following all standard of care therapies for advanced breast cancer. OR
- Histologically or cytologically confirmed locally advanced or metastatic gastric cancer and HER2 IHC 3+ or positive for HER2 gene amplification OR
- Histologically or cytologically confirmed Stage IIIb or IV non-small cell lung cancer HER2 IHC 2+ or 3+ by local laboratory assessment.
Exclusion Criteria:
- Major surgery, radiation therapy, or systemic anti-cancer therapy within 28 days of starting study treatment.
- Some types of brain metastases
- Peripheral neuropathy of Grade 2 within 3 weeks prior to the first study therapy
- History of exposure to cumulative doxorubicin dose ≥ 360 mg/meter squared. If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/meter squared of doxorubicin
- History of clinically significant cardiac dysfunction
- Current known active infection with HIV, hepatitis B virus, or hepatitis C virus
- Current severe, uncontrolled systemic disease
- Severe dyspnea at rest, due to complications of advanced malignancy, or requiring supplementary oxygen therapy.
- History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome
Patients who participate in the dose escalation segment of the study cannot participate in the expansion segment of the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dose Escalation and Confirmation
XMT-1522 treatment will administered in groups of patients who will receive doses that increase over time.
Once the maximum tolerated dose or recommended Phase 2 dose is achieved, new groups of patients will receive XMT-1522 at this fixed dose.
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one intravenous dose administered in-clinic every 21 days
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose or recommended Phase 2 dose
Time Frame: Up to 14 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met.
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Evaluate adverse events and use of concomitant medication use after XMT-1522 doses
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Up to 14 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time of maximum observed concentration of XMT-1522
Time Frame: Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses
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Determine the pharmacokinetics of XMT-1522
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Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses
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Maximum concentration of XMT-1522
Time Frame: Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses
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Determine the pharmacokinetics of XMT-1522
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Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses
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Area under the concentration curve of the last measurable concentration of XMT-1522
Time Frame: Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses
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Determine the pharmacokinetics of XMT-1522
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Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses
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Antineoplastic effects of XMT-1522
Time Frame: Every 6 weeks up to 12 months
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Monitor tumor size
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Every 6 weeks up to 12 months
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Anti-drug antibody
Time Frame: Before first dose, 21 and 42 days after first dose, and every 42 days until end of study which is estimated to be 100 days (14 weeks) after first dose
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Analyze blood for antibodies to XMT-1522 and neutralizing antibodies
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Before first dose, 21 and 42 days after first dose, and every 42 days until end of study which is estimated to be 100 days (14 weeks) after first dose
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Eric P. Hailman, MD, PhD, Mersana Therapeutics, Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- XMT-1522-1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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