Clinical Trials /

Study of Antibody Drug Conjugate in Patients With Advanced Breast Cancer Expressing HER2

NCT02952729

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Gastric Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Antibody Drug Conjugate in Patients With Advanced Breast Cancer Expressing HER2
  • 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

Clinical Trial IDs

  • ORG STUDY ID: XMT-1522-1
  • NCT ID: NCT02952729

Conditions

  • Advanced Breast Cancer
  • Advanced Nonsmall Cell Lung Cancer
  • Advanced Gastric Cancer

Interventions

DrugSynonymsArms
XMT-1522Dose Escalation and Confirmation

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation and ConfirmationExperimentalXMT-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.
  • XMT-1522

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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.
Safety Issue:
Description:Evaluate adverse events and use of concomitant medication use after XMT-1522 doses

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1522
Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1522
Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1522
Measure:Antineoplastic effects of XMT-1522
Time Frame:Every 6 weeks up to 12 months
Safety Issue:
Description:Monitor tumor size
Measure: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
Safety Issue:
Description:Analyze blood for antibodies to XMT-1522 and neutralizing antibodies

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mersana Therapeutics

Last Updated

May 5, 2017