E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
A particular form of Lung Cancer in cases were no cure was achieved with at least 2 previous treatments |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041070 |
E.1.2 | Term | Small cell lung cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070308 |
E.1.2 | Term | Refractory 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 |
To investigate the efficacy of rovalpituzumab tesirine as third-line and later treatment for subjects with relapsed or refractory delta-like protein 3 (DLL3)-expressing small cell lung cancer (SCLC) |
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E.2.2 | Secondary objectives of the trial |
- To assess duration of response, clinical benefit rate and progression-free survival in subjects with relapsed or refractory DLL3-expressing SCLC treated with rovalpituzumab tesirine
- To assess the safety and tolerability of rovalpituzumab tesirine
- To characterize the pharmacokinetics of rovalpituzumab tesirine and incidence of anti-therapeutic antibodies (ATA) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult aged 18 years or older
2. Histologically confirmed small-cell lung cancer (SCLC) with documented disease progression after at least 2 prior systemic regimens, including at least one platinum-based regimen
3. DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment of banked or otherwise representative tumor tissue. Positive is defined as staining in ≥ 1% of tumor cells.
4. Measurable disease, defined as at least 1 tumor lesion ≥10 mm in the longest diameter or a lymph node ≥15 mm in short-axis measurement assessed by CT scan (RECIST v1.1)
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Minimum life expectancy of at least 12 weeks
7. Subjects with a history of central nervous system (CNS) metastases must have documentation of stable or improved status based on brain imaging for at least 2 weeks after completion of definitive treatment and within 2 weeks prior to first dose of Study Drug, off or on a stable dose of corticosteroids. Definitive treatment may include surgical resection, whole brain irradiation, and/or stereotactic radiation therapy
8. Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration
9. Satisfactory laboratory parameters:
a. Absolute neutrophil count (ANC) ≥ 1,500/μL
b. Platelet count ≥ 75,000/μL
c. Hemoglobin ≥ 8.0 g/dL
d. Serum total bilirubin ≤ 1.5X upper limit of normal (ULN) or ≤ 3X ULN for subjects with Gilbert’s disease
e. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5X ULN (≤ 5X ULN if evidence of hepatic involvement by malignant disease)
f. Serum creatinine ≤ 1.5X ULN or estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m^2 as calculated by the 4-variable Modification of Diet in Renal Disease (MDRD) study equation (GFR (mL/min/1.73 m^2) = 175 × (serum creatinine [mg/dL])–1.154 × (age [years])–0.203 × 0.742 (if female) × 1.212 (if African American)
10. Last dose of any prior therapy administered by the following time intervals before the first dose of study drug:
a. Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks
b. Immune-checkpoint inhibitors (i.e., anti-PD-1, anti-PD-L1, or anti-CTLA-4): 4 weeks
c. Other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies: 4 weeks (2 weeks with documented disease progression)
11. Females of childbearing potential must have a negative beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
a. Females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraception method during the study and for 1 year following the last dose of study drug. Effective birth control includes (a) combined, estrogen and progestogen containing, hormonal contraception (oral, intravaginal, transdermal); (b) progestogen-only hormonal contraception (oral, injectable, implantable); (c) intrauterine device; (d) intrauterine hormone-releasing system; (e) bilateral tubal occlusion; (f) vasectomised partner; and (g) sexual abstinence. |
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E.4 | Principal exclusion criteria |
1. Any significant medical condition, including any suggested by screening laboratory findings 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 (e.g., chronic obstructive pulmonary disease requiring hospitalization within 6 months) 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 (see Appendix 0) within 6 months prior to their first dose of study drug
3. Recent or ongoing serious infection, including:
a. Any active grade 3 or higher (per NCI CTCAE version 4.03) viral, bacterial, or fungal infection within 2 weeks of the first dose of the study drug. Routine antimicrobial prophylaxis is permitted.
b. Known seropositivity for or active infection by human immunodeficiency virus (HIV)
c. Active Hepatitis B (by surface antigen expression or polymerase chain reaction) or Hepatitis C (by polymerase chain reaction) infection or on hepatitis-related antiviral therapy within 6 months of first dose of study drug.
4. Women who are breastfeeding
5. Systemic therapy with corticosteroids at >20 mg/day prednisone or equivalent within 1 week prior to the first dose of study drug
6. History of another invasive malignancy that has not been in remission for at least 3 years. Exceptions to the 3 year limit include nonmelanoma skin cancer, curatively treated localized prostate cancer, and cervical cancer in situ on biopsy or squamous intraepithelial lesion on PAP smear
7. Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation, unless undergoing retreatment with rovalpituzumab tesirine in the context of this protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
- Objective response rate through the End of Treatment for DLL3 high and for DLL3 positive, per IHC assay specification subjects
- Overall survival for DLL3 high and for DLL3 positive, per IHC assay specification subjects |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
(42 ± 3 days after last dose) |
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E.5.2 | Secondary end point(s) |
1. Clinical Benefit Rate
2. Duration of response
3. Progression-free survival |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Duration of response for DLL3 high and for DLL3 positive subject, per IHC assay specification
2. Clinical Benefit Rate for DLL3 high and for DLL3 positive subjects, per IHC assay specification
3. Progression-free survival for DLL3 high and for DLL3 positive subjects, per IHC assay specification |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
France |
Germany |
Hungary |
Poland |
Spain |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |