Lung Caner Metastatic or Locally Advanced Non-Small Cell Lung Cancer
Conditions
Interventions
Subjects will be randomly assigned to one of the following treatment groups:
- Group 1: will receive a fixed dose of the study drug (dose of 5.6 mg per kg
body weight) every three weeks
- Group 2: w
Sponsors
Daiichi Sankyo Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Sign and date the tissue ICF and the main ICF, prior to the start of any study-specific qualification procedures. 2. Male or female subjects aged >=18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old). 3. Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiation. 4. Documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease. Subjects must have received both of the following: a. Prior treatment with osimertinib. Subjects receiving an EGFR TKI at the time of signing informed consent should continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1. b. Systemic therapy with at least 1 platinum-based chemotherapy regimen. 5. Documentation of an EGFR-activating mutation detected from tumor tissue or blood sample: exon 19 deletion or L858R. 6. At least 1 measurable lesion confirmed by BICR as per RECIST v1.1 (please refer to section 10.4 of the protocol) 7. Consented and willing to provide required tumor tissue of sufficient quantity (as defined in the Laboratory Manual) and of adequate tumor tissue content (as confirmed by hematoxylin and eosin [H&E] staining at the central laboratory).Required tumor tissue can be provided as either: a. Pretreatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy OR b. Archival tumor tissue collected from a biopsy performed within 3 months prior to signing of the tissue consent and since progression while on or after treatment with the most recent cancer therapy regimen. AND consent to provide a required on-study tumor biopsy. After approximately 15 on-study tumor biopsies in each arm have been collected, the Sponsor will notify the Investigator of a change to the requirement. 8. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening (see Section 10.3.3 of the protocol) 9. Has adequate bone marrow reserve and organ function based on local laboratory data within 14 days prior to Cycle 1 Day 1 (please refer to schedule in protocol, paragraph 5.1). 10. If the subject is a female of childbearing potential, she must have a negative serum pregnancy test at Screening and must be willing to use highly effective birth control, as detailed in Section 10.3.4 of the protocol, upon enrollment, during the Treatment Period, and for 7 months following the last dose of study drug. A female is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy) with surgery at least 1 month before the first dose or confirmed by follicle stimulating hormone (FSH) test. Please refer to section 8.4.2 of the protocol. Pregnancy Test for further details regarding confirmation of post-menopausal status. 11. Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration. 12. If male, the subject must be surgically sterile or
Exclusion criteria
Exclusion criteria: 1. Any previous or current histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy. 2. Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening. 3. Clinically severe respiratory compromise (based on Investigator*s assessment) resulting from intercurrent pulmonary illnesses including, but not limited to: a. Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months prior to of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease [COPD]), restrictive lung disease, pleural effusion); b. Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis); OR prior complete pneumonectomy. 4. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory or any form of immunosuppressive therapy prior to enrollment. Subjects who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study. 5. Evidence of any leptomeningeal disease. 6. Evidence of clinically active spinal cord compression or brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive or treated brain metastases who are asymptomatic (ie, without neurologic signs or symptoms and not requiring treatment with corticosteroids or anticonvulsants) may be included in the study. Subjects must have a stable neurologic status for at least 2 weeks prior to Cycle 1 Day 1. 7. Inadequate washout period prior to Cycle 1 Day 1, defined as: a. Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days; b. Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than EGFR TKI), <14 days or 5 half-lives, whichever is longer; c. Immune checkpoint inhibitor therapy <21 days; d. Major surgery (excluding placement of vascular access) <28 days; e. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days; or f. Chloroquine or hydroxychloroquine <14 days. 8. Prior treatment with an anti-human epidermal growth factor receptor 3 (HER3) antibody or single-agent topoisomerase I inhibitor. 9. Prior treatment with an antibody drug conjugate (ADC) that consists of any topoisomerase I inhibitor 10. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, Grade <=1 or baseline. Subjects with chronic Grade 2 toxicities may be eligible at the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee. 11. Has history of other active malignancy within 3 years prior to enrollment, except: a. Adequately treated non-melanoma skin cancer; b. Superficial bladder tumors (T
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. ORR (objective response rate) Description: ORR as assessed by blinded independent central review per response Evaluation Criteria in Solid Tumors v1.1. Time frame: Data are collected at baseline, then from the start of study treatment until documented disease progression or other protocol defined reason. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. DoR (Duration of Response) Description: DoR as assessed by blinded independent central review (BICR) and Investigator per response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Time frame: Data are collected at baseline, then from the start of study treatment until documented disease progression, death, lost to follow-up, or withdrawal by subject. 2. PFS (Progression-free survival) Description: PFS as assessed by BICR and Investigator per RECIST v1.1 Time frame: Data are collected at baseline, then from the start of study treatment until documented disease progression or other protocol defined reason. Death date is collected until the subject discontinues the study. 3. ORR (Objective Response Rate) Description: ORR as assessed by Investigator per RECIST v1.11. Time frame: Data are collected at baseline, then from the start of study treatment until documented disease progression or other protocol defined reason. 4. DCR (Disease control rates) Description: DCR as assessed by BICR and Investigator per RECIST v1.1 Time frame: Data are collected at baseline, then from the start of study treatment until documented disease progression or other protocol defined reason. 5. TTR (Time to Response) Description: as assessed by BICR and Investigator per RECIST v1.1 Time frame: Data are collected at baseline, then from the start of study treatment until documented disease progression or other protocol defined reason. Time frame: Data are collected at baseline, then from the start of study treatment until documented disease progression or other protocol defined reason. 6. Best percentage change in the sum of diameters (SoD) of measurable tumors Description: SoD as assessed by BICR and by Investigator per RECIST V1.1. Time frame: Data are collected at baseline, then from the start of study treatment until documented disease progression or other protocol defined reason. 7. OS (Overall Survival) Description: OS Time frame: Death date is collecte | — |
Countries
Netherlands
Outcome results
None listed