A Phase 2, Multicenter, Single-Arm Study of Trastuzumab Emtansine in Patients With HER2 IHC-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Received At Least One Prior Chemotherapy Regimen

Hoffmann-La Roche23 sites in 7 countries49 target enrollmentDecember 15, 2014

ConditionsNon-Small Cell Lung Cancer

InterventionsTrastuzumab Emtansine

DrugsTrastuzumab Emtansine

Overview

Phase: Phase 2
Intervention: Trastuzumab Emtansine
Conditions: Non-Small Cell Lung Cancer
Sponsor: Hoffmann-La Roche
Enrollment: 49
Locations: 23
Primary Endpoint: Percentage of Participants With Objective Response as Per Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v. 1.1)
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 2, multicenter study designed to evaluate the efficacy and safety of trastuzumab emtansine administered as a single-agent in participants with HER2-positive (HER2 IHC 2+ or HER2 IHC 3+) advanced or metastatic NSCLC. Participants will be treated with trastuzumab emtansine administered intravenously at a dose of 3.6 milligrams per kilogram (mg/kg) on Day 1 of 21-day cycles until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the Sponsor, whichever occurs first.

Registry

clinicaltrials.gov

Start Date

December 15, 2014

End Date

August 20, 2018

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically documented diagnosis of Stage IIIB not amenable to radical treatment or Stage IV NSCLC (pathological characterization must determine the non-squamous or squamous histological subtype as well as adenocarcinoma subtype classification)
•HER2 status of IHC 2+ or 3+ as determined by a Sponsor-designated central laboratory
•Prior treatment with at least one regimen of platinum-based (cisplatin or carboplatin) chemotherapy in the locally advanced or metastatic setting/recurrent NSCLC with documented disease progression by investigator assessment
•Participants with a known anaplastic lymphoma kinase (ALK) fusion oncogene (must be documented in the participant's chart) must have also experienced disease progression or intolerance with a first-line ALK Tyrosine Kinase Inhibitor (TKI) approved for the treatment of ALK fusion oncogene NSCLC (for example, crizotinib). Disease progression or intolerance must be documented
•Participants with a known mutation in the epidermal growth factor receptor (EGFR) gene (must be documented in the participant's chart) must have also experienced disease progression or intolerance with an EGFR TKI approved for the treatment of EGFR-mutant NSCLC (for example, gefitinib, erlotinib, afatinib). Disease progression or intolerance must be documented
•Measurable disease determined as per the RECIST v1.1
•Life expectancy of at least (\>/=) 12 weeks
•Adequate organ function
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
•Left ventricular ejection fraction (LVEF) \>/= 50 percent (%) by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan

Exclusion Criteria

•Cancer-Related Criteria:
•Any approved anti-cancer therapy less than or equal to (\</=) 21 days (including chemotherapy or hormonal therapy) before the first study treatment; the following exceptions are allowed: (1) TKIs approved for the treatment of NSCLC must be discontinued greater than (\>) 7 days prior to the first study treatment on D1C1 (The baseline computed tomography \[CT\] scan must be completed after discontinuation of TKIs); (2) Hormone-replacement therapy or oral contraceptives; (3) Anti-emetics, Granulocyte-colony stimulating factor (GCS-F), and prophylactic antibiotics according to local standards
•Investigational therapy participation in another clinical study with therapeutic intent \</= 21 days before first study treatment
•Previous irradiation is permitted if \>/=14 days since the last fraction of radiotherapy have elapsed before the first study treatment on Day 1 as long as a sufficient number of target lesions remain to allow for measurable disease as per RECIST v1.1
•Participants who have untreated brain metastases or are symptomatic; participants with treated brain metastases must have discontinued corticosteroid therapy and not have any neurological symptoms
•History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any excipient of the product
•History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin \> 500 milligram per meter-square (mg/m\^2); Epirubicin \> 900 mg/m\^2; Mitoxantrone \> 120 mg/m\^
•If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m\^2 doxorubicin
•Peripheral neuropathy of Grade \>/= 3 per the National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 (NCI CTCAE v. 4.0)
•History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those mentioned above

Arms & Interventions

Cohort IHC2+

Participants with HER2 IHC2-positive (IHC 2+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.

Intervention: Trastuzumab Emtansine

Cohort IHC3+

Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.

Intervention: Trastuzumab Emtansine

Outcomes

Primary Outcomes

Percentage of Participants With Objective Response as Per Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v. 1.1)

Time Frame: From Day 1 to disease progression (PD) or death from any cause, up to the clinical cutoff date (approximately 22 months)

Objective response is defined as a complete response (CR) or partial response (PR) determined on two consecutive assessments ≥ 4 weeks apart, based on investigator assessment according to RECIST, Version 1.1. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 millimeters (mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Secondary Outcomes

Overall Survival (OS)(From Day 1 to death from any cause, up to the study completion date (approximately 43 months))
Progression-Free Survival (PFS) as Per Investigator Assessment According to RECIST v. 1.1(From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months))
Volume of Distribution (Vss) for Trastuzumab Emtansine and Total Trastuzumab(Pre-dose & 30 minutes (min) post-infusion (inf.) on D1 of C1 & 3; post- inf. on D2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D1 of C 4 (C=21 days); at treatment discontin/early termination, up to primary analysis, approx. 22 months)
Percentage of Participants With Clinical Benefit as Per Investigator Assessment According to RECIST, v1.1(From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months))
Duration of Objective Response (DOR) Assessed According to RECIST v1.1(From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months))
Elimination Half-Life (t1/2) for Trastuzumab Emtansine and Total Trastuzumab(Pre-dose & 30 minutes (min) post-infusion (inf.) on D 1 of C 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D 1 of C 4 (C=21 days); at treatment discontin./early termination, up to primary analysis, approx. 22 months)
Percentage of Participants Who Died(From Day 1 to death from any cause, up to the study completion date (approximately 43 months))
Percentage of Participants With DOR Event of Disease Progression, Assessed According to RECIST v1.1(From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months))
Percentage of Participants With PFS Event of Disease Progression, as Per Investigator Assessment According to RECIST v. 1.1, or Death(From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months))
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)(From Day 1 to 30 days after last dose of study drug, up to the study completion date (approximately 43 months))
Maximum Observed Concentration (Cmax) for Trastuzumab Emtansine and Total Trastuzumab(Pre-dose (within 2 days) and 30 minutes (min) after end of infusion (infusion length= 100 min or less) on Day 1 of Cycles 1 and 3 (one cycle=21 days); at treatment discontinuation/early termination, up to primary analysis, approx. 22 months)
AUCinf for Trastuzumab Emtansine and Total Trastuzumab(Pre-dose & 30 minutes (min) post-infusion (inf.) on Day (D) 1 of Cycles (C) 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D1 of C2 & D1 of C 4 (C=21 D); at discontin./termination, up to primary analysis, approx. 22 months)
Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)(Pre-dose (within 2 days) on Day 1 of Cycles 1 and 3; at treatment discontinuation/early termination,up to primary analysis, approx. 22 months)
Clearance (CL) for Trastuzumab Emtansine and Total Trastuzumab(Pre-dose & 30 minutes (min) post-infusion (inf.) on D 1 of C 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D 1 of C 4 (C=21 days); at treatment discontin/early termination, up to primary analysis, approx. 22 months)
Maximum Observed Concentration (Cmax) for N2'- Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1)(Pre-dose (within 2 days) and 30 minutes (min) after end of infusion (infusion length= 100 min or less) on Day 1 of Cycle 1 (one cycle=21 days); at treatment discontinuation/early termination,up to primary analysis, approx. 22 months)