HER-2 Mutated Metastatic Non-Small Cell Lung Cancer Lung Cancer
Conditions
Interventions
Subjects will be Randomly assigned to one of the following treatment groups:
- Group 1, approximately 100 subjects will receive 5.4 mg/kg of the study drug
- Group 2, approximately 50 subjects will r
Sponsors
Daiichi Sankyo Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Must have provided informed consent for study participation (see Section 10.1.2 of the protocol) 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, see Table 10.2 of the protocol). 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 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 block 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 left ventricular ejection fraction (LVEF) >= 50% within 28 days before randomization. 9. Has adequate organ function within 14 days before randomization (please refer to additional information in the protocol, paragraph 5.1). 10. Has adequate treatment washout period before randomization (please refer to additional information in the protocol, paragraph 5.1) 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 4 months for males, after the last dose of study drug. Methods considered as highly effective methods of contraception are described in Section 5.1 of the protocol. 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 throughout 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.
Exclusion criteria
Exclusion criteria: Has a known driver mutation in the epidermal growth factor receptor (EGFR), BRAF or MET exon 14 gene or a known anaplastic lymphoma kinase (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 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 central nervous system 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 intravenous (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 Grade
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy endpoint is confirmed ORR, defined as the proportion of subjects with CR or PR, assessed by the blinded independent central review (BICR) based on RECIST version 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| - Confirmed ORR as indicated above assessed by investigator assessment based on RECIST v.1.1. - DoR, defined as time from the initial response (CR or PR) by BICR and investigator assessment until documented tumor progression or death from any cause. - DCR, defined as the proportion of subjects who achieve CR, PR, or stable disease (SD) during study treatment. DCR based on BICR and DCR based on investigator assessments will both be determined. - PFS, defined as the time from date of randomization until first objective radiographic tumor progression or death from any cause, based on BICR and investigator assessment - OS, defined as the time from date of randomization until death from any cause. - Adverse Events (AEs) including TEAEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) that will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 - Physical examination findings that may include Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), vital sign measurements, ophthalmologic findings, standard clinical laboratory parameters, electrocardiogram (ECG) parameters, echocardiogram (ECHO)/multi-gated acquisition (MUGA) findings, and radiologic findings. - The PK endpoints include serum concentrations of Trastuzumab deruxtecan, total anti-HER2 antibody, and MAAA 1181a. - The immunogenicity endpoint includes incidence of ADA. The (patient-reported outcomes) PROs include: - Change from baseline in European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQC30) and EORTC quality of life questionnaire for lung cancer trials (QLQLC13) scale scores - Time to definitive deterioration in EORTC QLQ-C30 scores | — |
Countries
Netherlands
Outcome results
None listed