Small Cell Lung Cancer
Conditions
Keywords
Extensive-Stage Small Cell Lung Cancer (ED SCLC), Cancer, Platinum-Based Chemotherapy, Rovalpituzumab tesirine, first-line chemotherapy, Small Cell Lung Cancer (SCLC), Delta-like protein 3 (DLL3)
Brief summary
This is a Phase 3, randomized, double-blind, placebo-controlled, multinational, and multicenter study to evaluate the efficacy of rovalpituzumab tesirine as maintenance therapy following first-line platinum-based chemotherapy.
Interventions
DRUGPlacebo for dexamethasone
Placebo for dexamethasone PO twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6 week cycle, omitting every third cycle.
DRUGPlacebo for rovalpituzumab tesirine
Placebo for rovalpituzumab tesirine administered intravenously Day 1 of each 6-week cycle, omitting every third cycle
Rovalpituzumab tesirine 0.3 mg/kg administered intravenously Day 1 of each 6-week cycle, omitting every third cycle
DRUGDexamethasone
Dexamethasone 8 mg administered orally (PO) twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6 week cycle, omitting every third cycle.
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed extensive-stage disease small cell lung cancer (ED SCLC) at initial diagnosis with ongoing clinical benefit (stable disease \[SD\], partial response \[PR\], or complete response \[CR\]) following completion of 4 cycles of first-line platinum-based therapy * Participant 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 * Availability of archived or representative tumor material for assessment of DLL3 expression
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 for SCLC. * Any disease-directed radiotherapy (except prophylactic cranial irradiation, 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-based) 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Participants With Extensive-Stage Small Cell Lung Cancer With Delta-Like Protein 3 High Expression in Tumor (DLL3high) | Survival follow-up continued until the endpoint of death, participant was lost to follow-up or withdrew consent, or termination of the study by AbbVie, whichever occurred first. Median time on study overall was 11.9 months. | OS is defined as the number of months from randomization to death of any cause. Calculated using the Kaplan-Meier methodology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS in All Randomized Participants | Survival follow-up continued until the endpoint of death, the subject was lost to follow-up or withdrew consent, or termination of the study by AbbVie, whichever occurred first. Median time on study overall was 11.9 months. | OS is defined as the number of months from randomization to death of any cause. Calculated using the Kaplan-Meier methodology. |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Baseline, Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, Final Visit (up to Week 78) | The EORTC QLQ-C30 is composed of global health status/QoL scale; five functional domains (physical, role, emotional, cognitive, and social); three symptom domains (fatigue, nausea and vomiting, and pain); and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The Physical Functioning domain includes 5 questions in which participants were asked to rate their overall health and overall quality of life as it relates to physical functioning during the past week on a scale from 1 (very poor) to 7 (excellent). The 5 scores were averaged and transformed to a scale from 0 to 100, where a high score represents a high QoL. A positive change from baseline indicates better quality of life. |
Countries
Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Mexico, Netherlands, Norway, Poland, Portugal, Russia, Serbia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo every 6 weeks (q6 wk); omitting every third cycle
Placebo for rovalpituzumab tesirine: Placebo for rovalpituzumab tesirine administered intravenously Day 1 of each 6-week cycle, omitting every third cycle
Placebo for dexamethasone: Placebo for dexamethasone administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6 week cycle, omitting every third cycle | 376 |
| Rovalpituzumab Tesirine/Dexamethasone Rovalpituzumab tesirine/dexamethasone q6 wk; omitting every third cycle
Rovalpituzumab tesirine: Rovalpituzumab tesirine 0.3 mg/kg administered intravenously Day 1 of each 6-week cycle, omitting every third cycle
Dexamethasone: Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6 week cycle, omitting every third cycle | 372 |
| Total | 748 |
Baseline characteristics
| Characteristic | Placebo | Rovalpituzumab Tesirine/Dexamethasone | Total |
|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 8.2 | 64.1 years STANDARD_DEVIATION 8.4 | 63.9 years STANDARD_DEVIATION 8.29 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 66 Participants | 55 Participants | 121 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 18 Participants | 15 Participants | 33 Participants |
| Race/Ethnicity, Customized Missing | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Multiple Races | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 356 Participants | 355 Participants | 711 Participants |
| Race/Ethnicity, Customized White | 301 Participants | 314 Participants | 615 Participants |
| Sex: Female, Male Female | 137 Participants | 114 Participants | 251 Participants |
| Sex: Female, Male Male | 239 Participants | 258 Participants | 497 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 201 / 376 | 226 / 372 |
| other Total, other adverse events | 248 / 373 | 315 / 368 |
| serious Total, serious adverse events | 87 / 373 | 157 / 368 |
Outcome results
Primary
Overall Survival (OS) in Participants With Extensive-Stage Small Cell Lung Cancer With Delta-Like Protein 3 High Expression in Tumor (DLL3high)
OS is defined as the number of months from randomization to death of any cause. Calculated using the Kaplan-Meier methodology.
Time frame: Survival follow-up continued until the endpoint of death, participant was lost to follow-up or withdrew consent, or termination of the study by AbbVie, whichever occurred first. Median time on study overall was 11.9 months.
Population: DLL3 High Set: all randomized participants with extensive-stage small cell lung cancer with delta-like protein 3 high expression in tumor (DLL3high), defined as ≥ 75% tumor cells staining positive according to the VENTANA DLL3 \[SP347\] immunohistochemistry \[IHC\] assay.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Overall Survival (OS) in Participants With Extensive-Stage Small Cell Lung Cancer With Delta-Like Protein 3 High Expression in Tumor (DLL3high) | 9.79 months |
| Rovalpituzumab Tesirine/Dexamethasone | Overall Survival (OS) in Participants With Extensive-Stage Small Cell Lung Cancer With Delta-Like Protein 3 High Expression in Tumor (DLL3high) | 8.48 months |
p-value: 0.53795% CI: [0.84, 1.36]Log Rank
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time
The EORTC QLQ-C30 is composed of global health status/QoL scale; five functional domains (physical, role, emotional, cognitive, and social); three symptom domains (fatigue, nausea and vomiting, and pain); and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The Physical Functioning domain includes 5 questions in which participants were asked to rate their overall health and overall quality of life as it relates to physical functioning during the past week on a scale from 1 (very poor) to 7 (excellent). The 5 scores were averaged and transformed to a scale from 0 to 100, where a high score represents a high QoL. A positive change from baseline indicates better quality of life.
Time frame: Baseline, Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, Final Visit (up to Week 78)
Population: Randomized Set: all randomized participants, grouped according to the treatment arm to which they were randomized regardless the actual treatment received. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 48 | -6.67 score on a scale | — |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 30 | 5.33 score on a scale | Standard Error 4.22 |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 54 | -6.67 score on a scale | — |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 60 | 0.00 score on a scale | — |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 12 | -1.70 score on a scale | Standard Error 1.67 |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 66 | 0.00 score on a scale | — |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 36 | -13.33 score on a scale | — |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 72 | 0.00 score on a scale | — |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 78 | 0.00 score on a scale | — |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 24 | -0.95 score on a scale | Standard Error 7.32 |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week Final Visit | -4.14 score on a scale | Standard Error 1.02 |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 6 | -3.97 score on a scale | Standard Error 1 |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 42 | -6.67 score on a scale | — |
| Placebo | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 18 | 8.15 score on a scale | Standard Error 4.02 |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week Final Visit | -13.31 score on a scale | Standard Error 1.12 |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 6 | -4.34 score on a scale | Standard Error 0.95 |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 12 | -12.13 score on a scale | Standard Error 1.27 |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 18 | -19.52 score on a scale | Standard Error 4.92 |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 24 | -19.39 score on a scale | Standard Error 6.61 |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 30 | -16.67 score on a scale | Standard Error 6.78 |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 36 | -13.33 score on a scale | — |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 42 | -3.33 score on a scale | — |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 48 | -63.33 score on a scale | — |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 60 | 0.00 score on a scale | — |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 66 | 0.00 score on a scale | — |
| Rovalpituzumab Tesirine/Dexamethasone | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | Change at Week 78 | 0.00 score on a scale | — |
Comparison: Change at Week 695% CI: [-3.08, 2.35]
Comparison: Change at Week 1295% CI: [-14.58, -6.29]
Comparison: Change at Week 1895% CI: [-46.19, -9.16]
Comparison: Change at Week 2495% CI: [-38.28, 1.39]
Comparison: Change at Week 3095% CI: [-42.63, -1.37]
Comparison: Change at Week 36
Comparison: Change at Week 42
Comparison: Change at Week 48
Comparison: Change at Week 60
Comparison: Change at Week 66
Comparison: Change at Week 78
Comparison: Change at Final Visit95% CI: [-12.16, -6.19]
Secondary
OS in All Randomized Participants
OS is defined as the number of months from randomization to death of any cause. Calculated using the Kaplan-Meier methodology.
Time frame: Survival follow-up continued until the endpoint of death, the subject was lost to follow-up or withdrew consent, or termination of the study by AbbVie, whichever occurred first. Median time on study overall was 11.9 months.
Population: Randomized Set: all randomized participants, grouped according to the treatment arm to which they were randomized regardless the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | OS in All Randomized Participants | 9.89 months |
| Rovalpituzumab Tesirine/Dexamethasone | OS in All Randomized Participants | 8.80 months |
p-value: 0.23795% CI: [0.92, 1.36]Log Rank