HER2 IHC-Positive (IHC 2 + or IHC 3 +), Locally Advanced or Metastatic Non-Small Cell Lung Cancer MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age >= 18 years - 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 - Patients with a known ALK fusion oncogene (must be documented in the patient'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 (e.g., crizotinib). Disease progression or intolerance must be documented - Patients with a known mutation in the EGFR gene (must be documented in the patient's chart) must have also experienced disease progression or intolerance with an EGFR TKI approved for the treatment of EGFR-mutant NSCLC (e.g., gefitinib, erlotinib, afatinib). Disease progression or intolerance must be documented. - Measurable disease determined as per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1 - Life expectancy >= 12 weeks - Adequate organ function - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - LVEF >= 50% by either echocardiogram (ECHO) or or multiple-gated acquisition (MUGA) - Use of highly effective contraception Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: Cancer-Related Criteria - Any approved anti-cancer therapy 7 days prior to the first study treatment on Cycle 1, Day 1 (The baseline computed tomography scan must be completed after discontinuation of TKIs); (2) Hormone-replacement therapy or oral contraceptives; (3) Anti-emetics, GCS-F, prophylactic antibiotics are allowed according to local standards - Investigational therapy participation in another clinical study with therapeutic intent = 14 days since the last fraction of radiotherapy have elapsed before the first study treatment on Day 1 of Cycle 1 as long as a sufficient number of target lesions remain to allow for measurable disease as per RECIST v1.1. - Patients who have untreated brain metastases or are symptomatic; patients 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 milligrams per meter square (mg/m2); Epirubicin > 900 mg/m2; Mitoxantrone > 120 mg/m2. If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin. - Current peripheral neuropathy of Grade >= 3 per the National Cancer Institute Common Toxicity Criteria for Adverse Events 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. Cardiopulmonary Function Criteria - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures - Severe dyspnea at rest due to complications of advanced malignancy or requiring current continuous oxygen therapy - Clinical history of active hemoptysis - Evidence of pneumonitis during screening - Current unstable ventricular arrhythmia requiring treatment - History of symptomatic congestive heart failure (CHF; New York Heart Association [NYHA] Classes II-IV) - History of myocardial infarction or unstable angina within 6 months of enrollment - History of a decrease in LVEF to <50% General Criteria - Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) - Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during the course of study treatment - Current pregnancy or lactation - Current known active infection with HIV, hepatitis B, or hepatitis C virus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of single-agent trastuzumab emtansine in patients with centrally confirmed HER2-immunohistochemistry (IHC) positive (IHC 2 + or IHC 3 +) locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior chemotherapy regimen, as measured by confirmed ORR based on investigator assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (see Appendix 3).;Secondary Objective: The secondary efficacy objectives for this study are as follows: • To evaluate progression-free survival (PFS), duration of response (DoR), and clinical benefit rate (CBR) according to RECIST v1.1 (see Appendix 3), based on investigator assessment • To evaluate overall survival (OS). The safety objective for this study is to evaluate the safety and tolerability of trastuzumab emtansine administered every 3 weeks (Q3W) as a single agent to patients with HER2 IHC positive (IHC 2 + or IHC 3 +) NSCLC. The pharmacokinetic (PK) objective for this study is to characterize the pharmacokinetics of trastuzumab emtansine and assess the anti-therapeutic antibody (ATA) responses to trastuzumab emtansine in patients with HER2 IHC-positive locally advanced or metastatic NSCLC.;Primary end point(s): Objective response rate, defined as a complete response (CR) or partial response (PR) determined on two consecutive assessments >= 4 weeks apart and based on investigator assessment according to RECIST v. 1.1 ;Timepoint(s) of evaluation of this end point: After three post-baseline tumor assessments (approximately 4.5 months) after last patient is enrolled | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free survival (PFS), defined as the time from first study treatment to first documented disease progression, by investigator assessment using RECIST v1.1 2. Duration of response (DOR), defined as the time from the initial documentation of objective response (CR or PR) to documented disease progression, using RECIST v1.1, or death from any cause 3. Serum concentrations of trastuzumab emtansine and total trastuzumab 4. Plasma concentration of N2-deacetyl-N2-(3-mercapto-1-oxopropyl)-maytansine (DM1) 5. Incidence of adverse events (AEs) 6. Overall survival (OS) 7. CBR, defined as the proportion of patients with a CR or PR or stable disease (using RECIST v1.1) at 6 months 8. ATA response to trastuzumab emtansine 9. Serum concentration of HER2 extracellular domain (ECD) 10. PK parameters (such as area under the concentration-time curve, maximum concentration, clearance, volume of distribution at steady-state, and half-life) from the patients with intense PK sampling (optional).;Timepoint(s) of evaluation of this end point: 1. From first study treatment to disease progression or death from any cause or study termination, up to approximately 18 months 2. From first documented objective response to disease progression or death from any cause or study termination, up to approximately 18 months 3. and 8. Cycle 1 Day 1 and Cycle 3 Day 1; study treatment discontinuation or early termination visit, up to approximately 18 months 4. Cycle 1 Day 1 and Cycle 3 Day 1 5. and 6. From first study treatment to death from any cause or study termination, up to approximately 18 months 7. 6 months 9. cycle 1 Day 1 10. Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 4 or 5, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 4 Day 1. | — |
Countries
European Union, Germany, Italy, Korea, Republic of, Poland, Spain, Switzerland, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed