Advanced Breast CancerPhase 1NCT02952729
Study of Antibody Drug Conjugate in Patients With Advanced Breast Cancer Expressing HER2
A Phase 1 study testing XMT-1522 in people with Advanced Breast Cancer and Advanced Nonsmall Cell Lung Cancer, run by Mersana Therapeutics at 5 sites in United States.
Trial summary
This Phase 1b trial is an open label, multi-center study of XMT-1522 administered as an intravenous infusion once every three weeks. The dose escalation part of the study will establish the maximum tolerated dose or recommended Phase 2 dose for in patients with advanced breast cancer and either a HER2… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Breast Cancer, Advanced Nonsmall Cell Lung Cancer, Advanced Gastric Cancer
- What is being tested?
- XMT-1522
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 5 sitesUnited States
- Study dates
- 21 Nov 2016to 28 Jan 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Mary Crowley Cancer Research Center
Dallas, Texas, 75230
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, 78229
Moffitt Cancer Center
Tampa, Florida, 33607
About this study
Official title: 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
This Phase 1b trial is an open label, multi-center study of XMT-1522 administered as an intravenous infusion once every three weeks. The dose escalation part of the study will establish the maximum tolerated dose or recommended Phase 2 dose for in patients with advanced breast cancer and either a HER2 immunohistochemistry (IHC) score of at least 1+ using a validated IHC assay or with evidence of HER2 amplification. Patients with HER2 positive (by IHC or amplification) gastric cancer or nonsmall cell lung cancer may also be eligible for participation in dose escalation. Upon completion of dose escalation, the cohort expansion segment of the study will consist of four parallel cohorts of different patients groups to confirm the maximum tolerated dose or the recommended Phase 2 dose and estimate the objective response in each of the patient populations.
Read the 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
- Being tested
- XMT-1522
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XMT-1522Drug
one intravenous dose administered in-clinic every 21 days
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation and Confirmation | Experimental | 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. Receives: Drug: XMT-1522 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose or recommended Phase 2 dose
Evaluate adverse events and use of concomitant medication use after XMT-1522 doses
Measured: Up to 14 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met.
Secondary outcomes (5)
Time of maximum observed concentration of XMT-1522
Determine the pharmacokinetics of XMT-1522
Measured: 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
Maximum concentration of XMT-1522
Determine the pharmacokinetics of XMT-1522
Measured: 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
Area under the concentration curve of the last measurable concentration of XMT-1522
Determine the pharmacokinetics of XMT-1522
Measured: 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
Antineoplastic effects of XMT-1522
Monitor tumor size
Measured: Every 6 weeks up to 12 months
Anti-drug antibody
Analyze blood for antibodies to XMT-1522 and neutralizing antibodies
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2016 (estimated)
- Study start21 Nov 2016
- Primary completion28 Jan 2019
- Study completion28 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mersana Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eric P. Hailman, MD, PhD, Study director, Mersana Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02952729
- Sponsor's protocol ID
- XMT-1522-1
- Status last verified
- Feb 2021
- First submitted
- 27 Oct 2016
- Last updated
- 24 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02952729
- Acronym / sponsor ID
- XMT-1522-1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Mersana TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 21 Nov 2016 (actual)
- Primary completion
- 28 Jan 2019 (actual)
- Study completion
- 28 Jan 2019 (actual)
- First posted
- 2 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 1b trial is an open label, multi-center study of XMT-1522 administered as an intravenous infusion once every three weeks. The dose escalation part of the study will establish the maximum tolerated dose or recommended Phase 2 dose for in patients with advanced breast cancer and either a HER2 immunohistochemistry (IHC) score of at least 1+ using a validated IHC assay or with evidence of HER2 amplification. Patients with HER2 positive (by IHC or amplification) gastric cancer or nonsmall cell lung cancer may also be eligible for participation in dose escalation. Upon completion of dose escalation, the cohort expansion segment of the study will consist of four parallel cohorts of different patients groups to confirm the maximum tolerated dose or the recommended Phase 2 dose and estimate the objective response in each of the patient populations.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation and Confirmation | Experimental | Drug: XMT-1522XMT-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XMT-1522one intravenous dose administered in-clinic every 21 days | Drug | Dose Escalation and Confirmation |
Primary outcome
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.
Evaluate adverse events and use of concomitant medication use after XMT-1522 doses
5 secondary outcomes
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
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
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
Antineoplastic effects of XMT-1522
Time frame: Every 6 weeks up to 12 months
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric P. Hailman, MD, PhD study director
Mersana Therapeutics, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing XMT-1522 in people with Advanced Breast Cancer and Advanced Nonsmall Cell Lung Cancer, run by Mersana Therapeutics at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2021.