E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Small Cell Lung Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Non-Small Cell Lung Cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the OS of SG versus docetaxel. |
|
E.2.2 | Secondary objectives of the trial |
To compare the effect of SG versus docetaxel on the following: -PFS as assessed by the investigator per Response Evaluation Criteria in Solid Tumors -ORR as assessed by the investigator -DOR as assessed by the investigator -Disease control rate (DCR) as assessed by the investigator -Safety and tolerability -QOL using NSCLC Symptom Assessment Questionnaire |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria at screening/Day −1 to be eligible for participation in this study (no waivers for patient eligibility will be offered or permitted):
1) Female or male patients, 18 years of age or older, able to understand and give written informed consent 2) Life expectancy of 3 months or more 3) Pathologically documented NSCLC with documented evidence of Stage 4 NSCLC disease at the time of enrollment 4) EGFR, ALK, and PD-L1 results are required prior to enrollment (see Section 6.3.10). Resulting for other actionable genomic alterations is recommended and to be performed as per local standard of care and availability of targeted treatment. For patients with squamous cell carcinoma, EGFR and ALK testing is optional. 5) Must have progressed after platinum-based chemotherapy in combination with anti-PD-1/PD-L1 antibody OR platinum-based chemotherapy and anti-PD-1/PD-L1 antibody (in either order) sequentially. 6) Measurable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by the investigator in accordance with per RECIST Version 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Historical images within 28 days of the screening visit may be accepted as a screening image if deemed acceptable in the opinion of the investigator. 7) Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 (Appendix 5) before randomisation. 8) Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count ≥ 1500/mm3, and platelets ≥ 100,000/μL). 9) Adequate hepatic function (bilirubin ≤ 1.5 upper limit of normal [ULN], aspartate aminotransferase and alanine aminotransferase ≤ 2.5 ULN or ≤ 5 ULN if known liver metastases, and serum albumin > 3 g/dL). 10) Creatinine clearance of at least 30 mL/min as assessed by the Cockcroft-Gault equation 11) Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception |
|
E.4 | Principal exclusion criteria |
Patients who meet any of the following exclusion criteria at screening/Day −1 are not eligible to be enrolled in this study (no waivers for patient eligibility will be offered or permitted):
1) Mixed small-cell lung cancer and NSCLC histology 2) Positive serum pregnancy test or women who are lactating. 3) Known hypersensitivity to the study drugs, their metabolites, or formulation excipients 4) Requirement for ongoing therapy with or prior use of any prohibited medications for SG and docetaxel 5) Received a prior anticancer biologic agent within 4 weeks prior to enrollment or have received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment and have not recovered (ie, > Grade 2 is considered not recovered) from AEs at the time of study entry. Patients participating in observational studies are eligible 6) Have not recovered (ie, > Grade 2 is considered not recovered) from AEs due to a previously administered agent 7) Previously received treatment with any of the following: a) Topoisomerase 1 inhibitors. Any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase 1 b) Trop-2-targeted therapy c) Docetaxel as monotherapy or in combination with other agents 8) Active second malignancy 9) NSCLC that is eligible for definitive local therapy alone 10) Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc); any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren syndrome, sarcoidosis, etc); or prior pneumonectomy 11) Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to enrollment and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking 10 mg/day or less of prednisone or its equivalent. All patients with carcinomatous meningitis are excluded regardless of clinical stability 12) Met any of the following criteria for cardiac disease: a) Myocardial infarction or unstable angina pectoris within 6 months of enrollment b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation c) New York Heart Association Class III or greater congestive heart failure or left ventricular ejection fraction of less than 40% 13) Active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or gastrointestinal perforation within 6 months of enrollment 14) Active serious infection requiring antibiotics 15) Positive HIV-1 or HIV-2 antibody with detectable viral load OR taking medications that may interfere with SN-38 metabolism 16) Positive for hepatitis B surface antigen. Patients who test positive for hepatitis B core antibody will require hepatitis B virus DNA by quantitative polymerase chain reaction for confirmation of active disease 17) Positive hepatitis C antibody and detectable hepatitis C viral load 18) Other concurrent medical or psychiatric conditions that, in the investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations |
|
E.5 End points |
E.5.1 | Primary end point(s) |
OS is defined as the time from the date of randomization until death due to any cause in the Intent-to-Treat (ITT) Analysis Set. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monitored throughout the study |
|
E.5.2 | Secondary end point(s) |
- PFS is defined as the time from the date of randomization until the date of objective disease progression or death (whichever comes first) as assessed by the investigator per RECIST Version 1.1. - ORR is defined as the proportion of patients who achieve a complete response (CR) or PR that is confirmed at least 4 weeks later as assessed by the investigator per RECIST Version 1.1. - DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of PD or death from any cause (whichever comes first) as assessed by the investigator per RECIST Version 1.1. - DCR is defined as the proportion of patients who achieve a CR, PR, or stable disease (SD) as assessed by the investigator per RECIST Version 1.1. - Incidence of treatment-emergent adverse events (TEAEs) and clinical laboratory abnormalities. - Time to first deterioration in shortness of breath domain as measured by NSCLCSAQ. - Time to first deterioration in NSCLC-SAQ total score. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Monitored throughout the study |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 171 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Canada |
Mexico |
Austria |
France |
Poland |
Netherlands |
Spain |
Germany |
Greece |
Italy |
Belgium |
Hungary |
Portugal |
Turkey |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Individual Patients: Patients are considered to have reached the end of the study when they are no longer followed for long-term or survival follow-up due to the following reasons: death, patient withdrew consent, lost to follow-up, the sponsor terminated study, or completion of survival follow-up, whichever comes first. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 20 |