E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Extensive Stage Small Cell Lung Cancer (ED SCLC) |
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E.1.1.1 | Medical condition in easily understood language |
Extensive Stage Small Cell Lung Cancer (ED SCLC) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
To evaluate if rovalpituzumab tesirine improves progression-free survival, assessed by a Central Radiographic Assessment Committee (CRAC) according to RECIST v1.1, and overall survival in subjects with extensive-stage small cell lung cancer (ED SCLC) tumors with a high level of DLL3 expression (DLL3high) who have ongoing clinical benefit (SD, PR, or CR) following first-line platinum-based chemotherapy (cisplatin or carboplatin plus irinotecan or etoposide) compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
To evaluate if rovalpituzumab tesirine improves progression-free survival by CRAC and overall survival in all randomized subjects compared to placebo. To assess change in patient reported outcomes (PRO) with physical functioning as measured by the EORTC QLC-C30 questionnaire in all randomized subjects compared to placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically or cytologically confirmed ED SCLC (extensive stage disease at initial diagnosis) with ongoing clinical benefit (SD, PR, or CR per RECIST v1.1) following completion of 4 cycles of first-line platinum-based therapy (cisplatin or carboplatin in combination with etoposide or irinocetan). • Subject is eligible to be randomized at least 3 but no more than 9 weeks from Day 1 of the fourth cycle of first-line platinum-based chemotherapy. • Participants with a history of central nervous system (CNS) metastases prior to the initiation of first-line platinum-based chemotherapy must have received definitive local treatment and have documentation of stable or improved CNS disease status • Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 • Participants must have adequate bone marrow, renal and hepatic function |
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E.4 | Principal exclusion criteria |
• Any prior systemic chemotherapy, small molecule inhibitors, immune checkpoint inhibitors, other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, T-cell or other cell-based or biologic therapies, or any other anti-cancer therapy than that described in inclusion criteria 3-5 for SCLC • Any disease-directed radiotherapy (except, PCI, palliative radiotherapy to a radiographically documented non-progressing lesion for symptom control, or pre-planned radiotherapy for CNS metastases present prior to start of first-line therapy and non-progressing) after last dose of first-line chemotherapy. • Prior exposure to a pyrrolobenzodiazepine (PBD)- or indolinobenzodiazepine-based drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity or other contraindications to rovalpituzumab tesirine or excipient contained in the drug formulation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) and overall survival (OS) in subjects with DLL3 high ED SCLC are the two primary efficacy endpoints. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS - From randomization to disease progression, or death of any cause, whichever occurs first. OS - From randomization to death of any cause |
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E.5.2 | Secondary end point(s) |
- OS - PFS per the CRAC based on RECIST v1.1 - EORTC QLQ-C30 physical functioning domain - Objective response rate (ORR) per the CRAC and investigator assessment, respectively - Clinical benefit rate (CBR) per the CRAC and investigator assessment, respectively - Duration of response (DOR) per the CRAC and investigator assessment, respectively Response assessment will be based on RECIST v1.1. - Change from baseline in all PRO domains (except physical functioning) measured by EORTC QLQ-C30/LC13 and EQ-5D-5L - Safety endpoints will be summarized using data from the Safety set. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Disease progression will be defined as radiographic progression of disease by RECIST version 1.1. PFS, ORR, CBR, DOR - From randomization to disease progression, or death of any cause, whichever occurs first. Changes in PROs - From baseline (the assessment prior to first dose) to disease progression, or death of any cause, whichever occurs first. Safety endpoints - From baseline to specified time points throughout the study. |
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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 |
Quality of life Performance Status (ECOG) Healthcare Resource Utilization |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 115 |
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 |
Belarus |
Brazil |
Canada |
China |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Serbia |
South Africa |
Switzerland |
Taiwan |
Turkey |
Ukraine |
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 last subject's last visit. The sponsor may also end the study upon confirmation that the primary endpoint was statistically met. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |