Non-squamous nonsmall cell lung cancer Lung cancer Non-small cell lung cancer
Conditions
Interventions
None listed
Sponsors
Daiichi Sankyo, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Sign and date the main ICF, prior to the start of any study-specific qualification procedures. Consent for the optional samples for EOT tumor biopsy and/or pharmacogenetic analysis will be covered in the main ICF. A separate tissue screening consent will be obtained from all subjects to meet the baseline biopsy requirement. 2. Is a male or female subject aged >=18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old). 3. Has histologically or cytologically documented metastatic or locally advanced nonsquamous NSCLC not amenable to curative surgery or radiation. 4. Has documentation of an EGFR-activating mutation detected from tumor tissue or from blood sample: exon 19 deletion or L858R at diagnosis or thereafter. 5. Received 1 or 2 prior line(s) of an approved EGFR TKI treatment in the metastatic or locally advanced setting, which must include a thirdgeneration EGFR TKI (ie, approved therapies designed with higher preferential activity for mutant vs. EGFRwt and that address acquired resistance to first- and second-generation EGFR TKI [eg, osimertinib, lazertinib, aumolertinib, alflutinib, and others in consultation with Medical Monitor]). If a subject has received 2 prior lines of EGFR TKI therapy, administration of the third-generation EGFR TKI must have been in the most recent line. Subject must have documentation of T790M mutation if subjects had treatment with a first- or second-generation EGFR TKI prior to treatment with a third-generation EGFR TKI. Enrollment of subjects receiving third-generation EGFR TKIs other than osimertinib will be a maximum of approximately 20% of the enrolled population in each treatment arm. 6. May have received either neoadjuvant and/or adjuvant treatment if progression to metastatic or locally advanced disease occurred at least 12 months after the last dose of such therapy and subsequently experienced disease progression on or after third-generation EGFR TKI treatment administered in the metastatic or locally advanced setting. a. To provide an example, a patient who received osimertinib as adjuvant therapy after tumor resection, then progressed to having metastatic disease over a year following completion of adjuvant therapy must have also received a third-generation EGFR TKI as treatment for metastatic disease to be considered eligible for this study. 7. Has not received any other prior systemic therapies in the metastatic or locally advanced setting (including chemotherapy, immunotherapy etc) (even if administered in combination with EGFR TKI). 8. Has documentation of radiographic disease progression while receiving or after a third-generation EGFR TKI for metastatic or locally advanced disease. 9. Has at least 1 measurable lesion as per RECIST v1.1 by Investigator assessment. 10. Is willing to provide sufficient quantity and quality of tumor tissue content. 11. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening. 12. Has adequate bone marrow reserve and organ function based on local laboratory data within 14 days prior to randomization as described in the protocol. 13. If the subject is a female of childbearing potential, must have a negative serum pregnancy test at Screening and must be willing to use highly eff
Exclusion criteria
Exclusion criteria: 1. Has any previous histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy, or squamous NSCLC histology. 2. Has any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during Screening. 3. Has clinically severe respiratory compromise (based on the Investigator's assessment) resulting from intercurrent pulmonary illnesses as described in the protocol. 4. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to randomization. Subjects who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study. 5. Has any history of or evidence of current leptomeningeal disease. 6. Has evidence of clinically active spinal cord compression or brain metastases, defined as being symptomatic and untreated, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive or treated brain metastases who are asymptomatic (i.e., without neurologic signs or symptoms and not requiring treatment with corticosteroids or anticonvulsants) may be included in the study but must have a stable neurologic status for at least 2 weeks prior to randomization. Subjects with asymptomatic brain metastases and treated with anticonvulsants as prophylaxis are able to enrol. 7. Has had inadequate washout period prior to randomization defined as follows: a. Whole brain radiation therapy 30% of the bone marrow or with a wide field of radiation 2 for at least 3 months prior to randomization and managed with SoC treatment]) that the Investigator deems related to previous anticancer therapy may be randomized. 10. Has history of other active malignancy within 3 years prior to randomization, except the following: a. Adequately resected nonmelanoma skin cancer. b. Adequately treated intraepithelial carcinoma of the cervix. c. Any other curatively treated in situ disease. 11. Has uncontrolled or significant cardiovascular disease prior to randomization as described in the protocol. 12. Has active hepatitis B and/or hepatitis C infection, such as those with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS as assessed by BICR based on RECIST v1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| -Overall survival -PFS as assessed by the Investigator per RECIST v1.1 -PFS2 as assessed by local standard clinical practice -ORR as assessed by BICR and as assessed by the Investigator per RECIST v1.1 -DoR as assessed by BICR and as assessed by the Investigator per RECIST v1.1 -CBR as assessed by BICR and as assessed by the Investigator per RECIST v1.1 -DCR as assessed by BICR and as assessed by the Investigator per RECIST v1.1 -TTR as assessed by BICR and as assessed by the Investigator per RECIST v1.1 -Change from baseline for 5 symptoms assessed by NSCLC-SAQ, and 5 functioning scales and global health status and overall quality of life assessed by EORTC QLQC30 -Descriptive statistics of safety endpoints -Descriptive summary of baseline tumor tissue HER3 status and a correlative analysis between HER3 protein expression level and efficacy -ADA prevalence and incidence. ADA is measured in the serum via a validated assay. -Intracranial PFS as assessed by BICR per CNS-RECIST | — |
Countries
Netherlands
Outcome results
None listed