E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 10041067 |
E.1.2 | Term | Small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess treatment with rovalpituzumab tesirine imrpoves overall survival rate (OS) compared to topotecan in subjects with DLL3high SCLC who have first disease progression during or following front-line platinum based chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
- Assess if treatment with rovalpituzumab tesirine improves progression free survivial (PFS) compared to topotecan in subjects with advanced or metastatic DLL3high SCLC who have first disease progression during or following front-line platinum based chemotherapy, - To assess the pharmacokinetics (PK) and immunogenicity of rovalpituzumab tesirine, - Assess the effect on patient reported outcomes (i.e. health-related quality of life and symptom assessment) due to treatment with rovalpituzumab tesirine compared to topotecan in subects with DLL3high SCLC who have first disease progression during or following front-line platinum based chemotherapy. - To assess if the treatment with rovalpituzumab tesirine improves objective response rate and clinical benefit rate compared to topotecan in subjects with DLL3high SCLC who have first disease progression during or following front-line platinum based chemotherapy - To compare the duration of objective response between two arms |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional Tumor Tissue at Time of Progression for Exploratory Research |
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E.3 | Principal inclusion criteria |
1) Subjects must be an age of 18 years or older, providing written informed consent 2) Histologically or cytologically confirmed advanced or metastatic SCLC with documented first disease progression after or during front-line platinum-based systemic regimen. 3) Tumor must have high DLL3 expression (DLL3high) defined as having > 75% tumor cells staining positive according to the VENTANA DLL3 (SP347) IHC Assay. Archived or fresh tumor material can be used for the DLL3 testing. 4) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5) Females of childbearing potential must have a negative serum pregnancy test result at Screening, and a negative urine pregnancy test at randomization. Females of non-childbearing potential (either postmenopausal or permanently surgically sterile) at Screening do not require pregnancy testing. |
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E.4 | Principal exclusion criteria |
1) Any significant medical condition that, in the opinion of the investigator or Sponsor, may place the subject at undue risk from the study, including but not necessarily limited to uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease or neurological disorder (e.g., seizure disorder active within 6 months) 2) Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III – IV within 6 months prior to their first dose of study drug. 3) Subject has known leptomeningeal metastases 4) Subject has Isolated CNS disease progression with no evidence of progression outside of CNS 5) Subject has more than one prior systemic therapy regimen for SCLC (prior systemic maintenance therapy following front-line platinum based regimen, administered as part of clinical trial is allowed) |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Overall Survival is defined as the time from the date of randomization to the date of death form any cause (i.e., date of subject's death - date of randomization +1). |
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E.5.2 | Secondary end point(s) |
- Progression-free survival (PFS) based on the CRAC per RECIST v1.1, - Duration of objective response (DOR) based on the CRAC per RECIST v1.1, - Patient reported outcomes (PROs). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- PFS is based on independent review of tumor assessment, defined as the time from randomization to documented CRAC-assessed disease progression or death from any cause (whichever occurs earlier). - DOR is defined as the time between the date of first response (CR or PR, whichever is recorded first) to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause, whichever comes first. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Performance status Quality of Life |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
Australia |
Brazil |
Canada |
China |
Japan |
Korea, Republic of |
Mexico |
Singapore |
Taiwan |
Turkey |
United States |
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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
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The end-of-study is defined as the date of the last subject's last visit, or the date of the last subject's last survival follow-up contact, whichever is later. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |