Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Myotonic Dystrophy Type 1

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Trastuzumab

Ado-Trastuzumab Emtansine

Adenosine

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

Tubulin Modulators

Antimitotic Agents

trastuzumab-MCC-DM1

Scott Holden, M.D.

This is a phase I, multicenter, open-label, dose-escalation study of single-agent trastuzumab-MCC-DM1 administered by intravenous (IV) infusion in patients with HER2-positive metastatic breast cancer (MBC) who have previously received trastuzumab. The study will assess the safety, tolerability, and pharmacokinetics of trastuzumab-MCC-DM1 and determine the dose and schedule to be used in Phase II.

A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen

A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Trastuzumab-MCC-DM1 (PRO132365) Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen

The time frame for AEs is study treatment initiation until 30 days after last administration of study treatment or at the time of initiation of another anti-cancer therapy, which ever occurs first.

The time frame for SAEs is study treatment initiation until 90 days after last administration of study treatment or at the time of initiation of another anti-cancer therapy, which ever occurs first.

DLT is defined as one of the following as per investigator related to study drug:

* Grade ≥ 3 non-hematologic, non-hepatic major organ toxicity
* Grade ≥ 3 cardiac toxicity, including cardiac troponin I elevation or any new segmental wall abnormality as determined by non-invasive cardiac imaging
* Grade ≥ 4 thrombocytopenia
* Grade ≥ 4 neutropenia (absolute neutrophil count \< 500/μ L) lasting \> 4 days or accompanied by fever
* Grade ≥ 4 anemia
* Grade ≥ 3 serum bilirubin, hepatic transaminase (alanine aminotransferase or aspartate aminotransferase), or alkaline phosphatase For patients with Grade 2 hepatic transaminase or alkaline phosphatase levels at baseline as a result of liver metastases or bone metastases, a hepatic transaminase or alkaline phosphatase level ≥ 10 times the upper limit of normal will be considered a DLT.
* Weekly cohorts only: Toxicity preventing retreatment on Cycle 1, Day 8 or toxicity preventing re-treatment on Cycle 1, Days 15 and Day 22

The highest dose level resulting in a DLT in ≤ 1 of 6 patients was declared the MTD.

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

The occurrence of an objective response was determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). An objective response was defined as a complete response or a partial response as determined on 2 consecutive occasions ≥ 4 weeks apart. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions.

Duration of objective response was defined as the time from the initial response to disease progression or death from any cause within 30 days of the last dose of trastuzumab emtansine.

Progression-free survival was defined as the time from first dose of trastuzumab emtansine to documented disease progression or death from any cause within 30 days of the last dose of trastuzumab emtansine, whichever occurred earlier. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter of target lesions recorded since treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

After the start of trastuzumab emtansine treatment, serum samples were collected every 3 weeks prior to trastuzumab emtansine dosing for detection of anti-therapeutic antibodies using a validated assay. A bridging antibody electrochemiluminescence assay (ECLA) was used to detect antibodies to trastuzumab emtansine. The assay utilized trastuzumab emtansine conjugated to biotin and a ruthenium label to form a complex with anti-trastuzumab emtansine antibodies. The antibody complex was captured by streptavidin-coated paramagnetic beads.

Genentech, Inc.

Trastuzumab-MCC-DM 0.3 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM 0.3 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM 0.6 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM 0.6 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM 1.2 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM 1.2 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM 2.4 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM 2.4 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM 3.6 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM 3.6 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM 4.8 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM 4.8 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM 1.2 mg/kg administered intravenously (IV) once a week

Trastuzumab-MCC-DM 1.2 mg/kg Weekly

Trastuzumab-MCC-DM 1.6 mg/kg administered intravenously (IV) once a week

Trastuzumab-MCC-DM 1.6 mg/kg Weekly

Trastuzumab-MCC-DM 2.0 mg/kg administered intravenously (IV) once a week

Trastuzumab-MCC-DM 2.0 mg/kg Weekly

Trastuzumab-MCC-DM 2.4 mg/kg administered intravenously (IV) once a week

Trastuzumab-MCC-DM 2.4 mg/kg Weekly

2.9 mg/kg administered intravenously (IV) once a week

Trastuzumab-MCC-DM 2.9 mg/kg Weekly

Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks

Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week

Trastuzumab-MCC-DM1 1.2 mg/kg Weekly

Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week

Trastuzumab-MCC-DM1 1.6 mg/kg Weekly

Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week

Trastuzumab-MCC-DM1 2.0 mg/kg Weekly

Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week

Trastuzumab-MCC-DM1 2.4 mg/kg Weekly

Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week

Trastuzumab-MCC-DM1 2.9 mg/kg Weekly

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

All summaries were based on data from the safety population (patients who received at least one dose of Trastuzumab-MCC-DM1). All summaries were presented for all patients and by dose level and schedule.

Medical Communications

At least 1 AE

AEs with Grade >=3

At least 1 SAE

AEs related to treatment

Safety-evaluable population: All participants who received at least 1 dose of trastuzumab-MCC-DM1

Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment

Efficacy population: All enrolled participants who received treatment.

Percentage of Participants With an Objective Response

Duration of Objective Response

Progression-free Survival

Pre-dose (Cycle 1, Day 1)

Any Visit after Dosing

Trastuzumab-MCC-DM1 0.3 to 4.8 mg/kg administered intravenously (IV) once every 3 weeks

Trastuzumab-MCC-DM1 Every 3 Weeks

Trastuzumab-MCC-DM1 1.2 to 2.9 mg/kg administered intravenously (IV) once every week

Trastuzumab-MCC-DM1 Every Weeks

Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine

Safety Population included all treated patients

Number of Patients With Dose Limiting Toxicities (DLTs)

Safety evaluable population: All participants who received at least 1 dose of trastuzumab-MCC-DM1

Maximum Tolerated Dose (MTD)

Pharmacokinetic-evaluable patients were defined as patients who received at least one dose of T-DM1 with at least one post-dose concentration data point.

Spots Global Cancer Trial Database for A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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Contact Details

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