Adult patients with metastatic and/or unresectable Non-Small Cell Lung Cancer (NSCLC) who progressed on at least one line and not more than three lines of prior therapy for metastatic/unresectable NSCLC MedDRA version: 21.1 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
Interventions
Product Code: DS-1062a
Pharmaceutical Form: Powder for concentrate for solution for injection/infusion
INN or Proposed INN: Datopotamab deruxtecan
Other descriptive name: DS-1062a
Concentration unit:
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years. 2. Patients with histologically confirmed diagnosis of advanced and/or unresectable NSCLC. 3. At least one line and not more than three lines of therapy and considered by the investigator as refractory to or progressed on standard treatment or for which no standard treatment is available: a. For patients who have no known mutation or mutation without an approved targeted therapy, must have received an anti PD-1/PD-L1 containing therapy and a platinum-doublet regimen. b. For patients who have known EGFR, BRAF, and MET mutation or ALK, ROS1, RET, NTRK fusion (if available): they must have progressed after one line of an approved targeted agent and one platinum-doublet regimen. 4. Patients must have metastatic site easily accessible to biopsy (with exception of bone metastasis) and must have accepted to perform pre-treatment, on-treatment and end-of-treatment biopsies. 5. Presence of at least one measurable lesion (different from the biopsy site) according to RECIST v1.1. 6. Patients must have an ECOG performance status =1 at the time of screening. 7. Patients must have a life expectancy of = three months. 8. Has adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1 defined as in the table in the protocol. 9. Patients with asymptomatic and clinically stable treated brain metastasis, who require no treatment with corticosteroids and/or anticonvulsants, and if they have recovered from the acute toxic effect of radiotherapy. 10. Females of reproductive/childbearing potential must have a negative serum pregnancy test at screening and 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 after the last dose of study drug. Methods considered as highly effective methods of contraception include: a. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: • Oral • Intravaginal • Transdermal b. Progestogen-only hormonal contraception associated with inhibition of ovulation: • Oral • Injectable • Implantable c. Intrauterine device (IUD) d. Intrauterine hormone-releasing system (IUS) e. Bilateral tubal occlusion f. Vasectomized partner g. Complete sexual abstinence defined as refraining from heterosexual intercourse during and upon completion of the study and for at least 7 months for females after the last dose of study drug. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception. Female patients 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. Male patients must be surgically sterile or must withhold heterosexual intercourse or must be willing to use a highly effective birth control upon enrollment, during the treatment period, and for at least 4 months following the last dose of study drug. Male patients must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration. 11. Patients must understand, sign and date the written informed consent from prior to any protocol-specific procedures performed. Patients should be able and willing to comply with study visits and procedures as per protocol. 12. Patients must be affiliate
Exclusion criteria
Exclusion criteria: 1.Patient unwilling to participate to the biological investigations (...) as required in the protocol. 2.Patient with only bone metastasis will be excluded, except if they have an accessible primary tumor which could be biopsied at baseline, on-treatment and end-of-treatment. 3.Patient with any history of ILD (...), has current ILD, or is suspected to have such disease by imaging during screening. 4.Patient with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to: any underlying pulmonary disorder (...)/any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (...)/OR prior pneumonectomy; 5.Patient receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Patients who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study. 6.Patient with evidence of any leptomeningeal disease. 7.Patient with evidence of clinically active spinal cord compression or brain metastases, (...), or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. (...). Patients must have a stable neurologic status for at least two weeks prior to Cycle 1 Day 1. 8.History of severe hypersensitivity reactions to either the drug substances or inactive ingredients (...) of DS-1062a. 9.History of severe hypersensitivity reactions to other monoclonal antibodies. 10.Inadequate washout period prior to Cycle 1 Day 1, defined as: Whole brain radiation therapy 470 ms for females and >450 ms for males (...) and assessed based on triplicate ECGs, approximately 1 minute apart. b.LVEF <50% by either ECHO or MUGA. c.Uncontrolled hypertension d.Myocardial infarction within 6 months. e.NYHA Classes 2 to 4 within 28 days. f.Uncontrolled angina pectoris within six months. g.Cardiac arrhythmia requiring antiarrhythmic treatment. 18. Active Hepatitis B and/or Hepatitis C infection, such a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective is to evaluate the overall anti-tumor activity of DS-1062a, as measured by objective response rate (ORR) based on investigator assessment, in patients with metastatic /unresectable NSCLC who have progressed on previous standard therapies for NSCLC.;Secondary Objective: a.To evaluate the efficacy of DS-1062a in terms of: •Duration of response (DoR) based on investigator assessment. •Progression Free Survival (PFS) based on investigator assessment. •Clinical benefit rate (CBR). •Overall survival (OS). b. To evaluate the safety and tolerability of DS-1062a, in terms of: •Frequency and severity of all adverse events (AEs), treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), defined by the NCI-CTCAE v5.0. •Treatment discontinuation, interruptions, and dose reductions due to any AEs. •Frequency and severity of laboratory abnormalities defined by NCI-CTCAE v5.0. •ECG abnormalities (including QT/QTc interval data) and Left Ventricular Ejection Fraction (LVEF) decrease (measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan defined by New York Heart Association (NYHA) functional classification. •ECOG performance status changes. ;Primary end point(s): The primary endpoint is to determine the ORR of DS-1062a in patients with advanced NSCLC. ORR is defined as the proportion of patients who achieved a confirmed complete response (CR) or partial response (PR) observed on treatment and assessed by investigators. Confirmation of response must be demonstrated with an assessment four weeks or later from the initial response. Treatment objective response will be radiologically assessed at three weeks after the first cycle and thereafter every six weeks using RECIST v1.1.;Timepoint(s) of evaluation of this end point: See above | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a. The efficacy endpoints will be evaluated using RECIST v1.1 with the following parameters: • DoR is applicable to patients with either CR or PR and is defined as the time from the first documented CR or PR until the date of disease progression, or until the date of death. • PFS is defined as the time from date of the first dose of DS-1062a until to the earlier of the dates of the first objective documentation of progression or death from any cause, whichever occurs first. At the time of analysis, the patient alive and without progression will be censored at the date of the last tumor assessment. • CBR is defined as the presence of at least a PR or CR, or a stable disease (SD) > six months under treatment. Reviewed RECIST v1.1 evaluation will be used. • OS is defined as the time from date of the first DS-1062a dose until death. Patients alive at last follow-up will be censored at this date. b. Safety and tolerability of DS-1062a will be evaluated continuously through frequency and severity of any AEs, TEAEs, SAEs, AESIs graded by NCI-CTCAE v5.0; proportion of treatment discontinuation, interruptions and dose reductions due to any AEs; frequency and severity of laboratory abnormalities defined by NCI-CTCAE v5.0; frequency and severity of QTcF prolongation; LVEF decrease or cardiac disfunction graded according to NYHA functional classification. ;Timepoint(s) of evaluation of this end point: See above | — |
Countries
France
Contacts
Public ContactSponsor Project Manager
Gustave Roussy
Outcome results
None listed