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

Advanced Breast Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02952729
• Other study ID #: XMT-1522-1
• Status: Completed
• Phase: Phase 1
• Start date: November 21, 2016
• Est. completion date: January 28, 2019

Study information

• Verified date: February 2021
• Source: Mersana Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: January 28, 2019
• Est. primary completion date: January 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Advanced Gastric Cancer
• Advanced Nonsmall Cell Lung Cancer
• Breast Neoplasms
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• XMT-1522
one intravenous dose administered in-clinic every 21 days

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Mersana Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose or recommended Phase 2 dose	Evaluate adverse events and use of concomitant medication use after XMT-1522 doses	Up to 14 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met.
Secondary	Time of maximum observed concentration of XMT-1522	Determine the pharmacokinetics of XMT-1522	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
Secondary	Maximum concentration of XMT-1522	Determine the pharmacokinetics of XMT-1522	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
Secondary	Area under the concentration curve of the last measurable concentration of XMT-1522	Determine the pharmacokinetics of XMT-1522	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
Secondary	Antineoplastic effects of XMT-1522	Monitor tumor size	Every 6 weeks up to 12 months
Secondary	Anti-drug antibody	Analyze blood for antibodies to XMT-1522 and neutralizing antibodies	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