HER2-mutated metastatic Non-Small Cell Lung Cancer (NSCLC) MedDRA version: 20.0 Level: LLT Classification code 10025044 Term: Lung cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Trastuzumab deruxtecan for injection 100 mg
Product Code: DS-8201a
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Trastuzumab deruxtecan
CAS N
Sponsors
Daiichi Sankyo, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must have provided informed consent for study participation (see Section 10.1.2) before performance of any study-specific procedure or test. 2. Men or women =18 years old. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 years old). 3. Pathologically documented metastatic NSCLC with a known activating HER2 mutation (please refer to the list of HER2 mutations, Table 10.2). The HER2 mutation must be documented from an archival or fresh tumor tissue sample analyzed by Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or equivalent laboratory performing testing to Good Laboratory Practice (GLP) standard. Note: HER2 mutation documented only from a liquid biopsy sample cannot be used for enrollment. 4. Subjects who had previous treatment (2L+) including platinum therapy in the metastatic/locally advanced setting and not amenable to curative surgery or radiation. The subject must have progressed during or after the last treatment regimen or discontinued because of unacceptable toxicity. 5. Presence of at least 1 measurable lesion confirmed by BICR based on RECIST version 1.1. 6. Is willing and able to provide an adequate archival tumor tissue sample. A fresh biopsy is required if an archival tumor tissue sample cannot be supplied. Resection and core needle biopsy are acceptable. Other tissue samples, eg, fine needle aspirates or cell blocks are not acceptable. For detailed instruction on tissue submission, please refer to the laboratory manual. 7. Has ECOG PS of 0 to 1. 8. Has LVEF = 50% within 28 days before randomization. 9. Has adequate organ function within 14 days before randomization, as defined in the protocol. 10. Has adequate treatment washout period before randomization, as defined in the protocol. 11. Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for females and for 4 months for males after the last dose of study drug. Please refer protocol for more details. 12. Male subjects must not freeze or donate sperm starting at randomization and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to randomization in this study. 13. Female subjects must not donate, or retrieve for their own use, ova from the time of randomization and throughout the study treatment period, and for at least 7 months after the final study drug administration. Female subjects must refrain from breastfeeding hroughout this time. Preservation of ova may be considered prior to randomization in this study. 14. Life expectancy of 3 months or more. Please refer to protocol for complete list of inclusion criteria. 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 135 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Has a known driver mutation in the EGFR, BRAF, or MET exon 14 gene or a known ALK, ROS1, RET, or NTRK fusion. 2. Medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any MI related symptoms should have a cardiologic consultation before randomization to rule out MI. 3. Has a corrected QT interval (QTcF) prolongation > 470 msec (females) or >450 msec (males) based on average of the triplicate12-lead ECG at screening. 4. Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. 5. Has spinal cord compression or clinically active CNS metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study randomization. 6. Has multiple primary malignancies within 3 years, except adequately resected non melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated. 7. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product. 8. Has a history of severe hypersensitivity reactions to other monoclonal antibodies. 9. Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. 10. Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject’s participation in the clinical study or evaluation of the clinical study results. 11. Known human immunodeficiency virus (HIV) infection. Subjects should be tested for HIV prior to randomization if required by local regulations or institutional review board (IRB)/independent ethics committee (IEC). 12. Known active clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C), such as those with serologic evidence of viral infection within 28 days of Cycle 1, Day 1. Subjects with past or resolved hepatitis B virus (HBV) infection are eligible, if negative for hepatitis B surface antigen (HBsAg[-]) and positive for hepatitis B core antibody (anti-HBc[+]). Subjects positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV RNA. 13. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia)not yet resolved to Grade = 1 or baseline. Note: Subjects may be enrolled with chronic Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to randomization and managed with standard of care treatment) which the investigator deems related to previous nticancer therapy, such as: a. Chemotherapy-induced neuropathy b. Fatigue c. Residual toxicities from prior IO treatment: Grade 1 or Grade 2 endocrinopathies which may includ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate confirmed ORR of trastuzumab deruxtecan in human epidermal growth factor receptor 2- (HER2-) mutated NSCLC subjects treated at 5.4 and 6.4 mg/kg doses.;Secondary Objective: • To evaluate the clinical efficacy of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses by confirmed ORR by investigator assessment. • To evaluate the clinical efficacy of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses by Duration of Response (DoR). • To evaluate further the clinical efficacy of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses by Disease control rate (DCR), Progression-free survival (PFS) and Overall survival (OS). • To evaluate safety of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses. • To evaluate pharmacokinetics (PK) and immunogenicity of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses. • To assess symptoms, functioning and Health-related Quality of life (HRQoL) in subjects treated with trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses. ;Primary end point(s): Primary efficacy endpoint is confirmed Objective Response Rate (ORR), defined as the proportion of subjects with Complete Response (CR) or Partial Response (PR), assessed by blinded independent central review (BICR) based on RECIST version 1.1;Timepoint(s) of evaluation of this end point: At least 9 months after the last subject is randomized | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Objective Response Rate - Duration of Response (DoR) - Disease Control Rate (DCR) - Progression-free Survival (PFS) - Overall Survival (OS) - Safety parameters (AEs, ECOG PS, vital signs, clinical laboratory parameters, ECG etc.) - PK endpoints: Serum concentrations of trastuzumab deruxtecan, total anti-HER2 antibody, and MAAA 1181a - Immunogenicity endpoint: Incidence of ADA. - Change from baseline in European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30) and EORTC quality of life questionnaire for lung cancer trials (QLQ-LC13) scale scores - Time to deterioration in EORTC QLQ-C30 scores;Timepoint(s) of evaluation of this end point: ORR, DOR, PFS, OS, Safety parameters, PK, Immunogenicity, Health-related Quality of life (HRQoL): At least 9 months after the last subject is randomized | — |
Countries
Australia, Canada, France, Italy, Japan, Korea, Republic of, Netherlands, Spain, Taiwan, United States
Contacts
Public ContactDavid Rusnak
Daiichi Sankyo Inc.
Outcome results
None listed