Small Cell Lung Cancer
Conditions
Keywords
SCLC, Small Cell Lung Cancer, DLL#, Relapsed, Refractory
Brief summary
The purpose of this study is to determine the efficacy of rovalpituzumab tesirine as a third-line and later treatment for participants with relapsed or refractory delta-like protein 3 (DLL3) expressing small cell lung cancer (SCLC).
Interventions
Rovalpituzumab tesirine is a DLL3 targeted antibody drug conjugate (ADC).
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult aged 18 years or older 2. Histologically confirmed 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 as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 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 8. Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration 9. Adequate hematologic and organ function as confirmed by laboratory values 10. Last dose of any prior therapy administered by the following time intervals before the first dose of study drug: * Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks * Immune-checkpoint inhibitors (i.e., anti-PD-1, anti-PD-L1, or anti-CTLA-4): 4 weeks * 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.
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 within 6 months prior to their first dose of study drug 3. Recent or ongoing serious infection, including: * Any active grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 4.03) viral, bacterial, or fungal infection within 2 weeks of the first dose of the study drug. Routine antimicrobial prophylaxis is permitted. * Known seropositivity for or active infection by human immunodeficiency virus (HIV) * Active Hepatitis B (by surface antigen expression or polymerase chain reaction) or 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks | Objective response is defined as a participant with the best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, prior to receiving any subsequent anticancer therapy and retreatment, and is confirmed by a consecutive response assessment at least 4 weeks (28 days) from the initial determination of CR/PR. Analyzed based on response assessments from both the Independent Review Committee (IRC) and investigators. CR: disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Overall Survival | up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks | Overall survival is defined as the time from the first dose date to death for any reason. Participants who were alive at the clinical data cut-off were censored at the last known alive date. Based on Kaplan-Meier estimates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks | Progression-free survival is defined as the time from the first dose date to the documented date of PD or death, whichever occurred first. Participants who neither progressed nor died were censored at the last evaluable disease assessment. Analyzed based on response assessments from both the IRC and investigators. Based on Kaplan-Meier estimates. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.) |
| Clinical Benefit Rate | up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks | Clinical benefit rate is defined as the percentage of participants with an overall response of CR or PR or stable disease (SD) with SD of a minimum duration of 42 days from the first dose date. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.) |
| Duration of Clinical Benefit | up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks | Duration of clinical benefit is defined as time from the date of first documented CR or PR or SD of ≥ 42 days from first dose date (-7 days to allow for scheduled visit window per the protocol) to the documented date PD or death, whichever occurs first. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Overall Response Rate | up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks | Overall response rate is defined as the percentage of participants with a response of CR or PR, regardless of confirmation, per RECIST v 1.1 prior to receiving any subsequent anticancer therapy and retreatment. Any participants not exhibiting a response (CR or PR) as defined above were considered non-responders. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Number of Anti-Therapeutic Antibody (ATA) Positive Participants | up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks | — |
| Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment | From first dose of study drug through the end of the initial treatment period (84 ± 6 days) | An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: is fatal or life-threatening; results in death or hospitalization; is disabling/incapacitating or a congenital anomaly/birth defect; is medically significant. AE severity was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03 terminology: grade 1=mild; grade 2=moderate; grade 3=severe; grade 4 life-threatening; grade 5=death. TEAEs were defined as AEs that were newly occurring or worsened following study treatment. |
| Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | From first dose of study drug through the end of the initial treatment period (84 ± 6 days) | TEAEs were defined as AEs that were newly occurring or worsened following study treatment. |
| Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 1, 30 minutes pre-infusion; Day 1, 30 minutes post-infusion; Day 3; Day 15; Day 29. Cycle 2: Day 1, 30 minutes pre-infusion; Day 1, 30 minutes post-infusion; Day 3; Day 15; Day 29; End of Treatment (up to Day 29). | — |
| Duration of Objective Response | up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks | Duration of objective response is defined as the time from the date of first documented CR or PR of participants with a confirmed response to the documented date of progressive disease (PD) or death, whichever occurred first. Participants who neither progressed nor died are censored at the last evaluable disease assessment. Analyzed based on response assessments from both the IRC and investigators. Based on Kaplan-Meier estimates. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.) |
Participant flow
Pre-assignment details
A total of 342 participants were enrolled; 3 participants were not dosed.
Participants by arm
| Arm | Count |
|---|---|
| Rovalpituzumab Tesirine 0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (Q6W) for 2 cycles. An additional 2 cycles of rovalpituzumab tesirine (retreatment) was permitted for eligible participants. | 339 |
| Total | 339 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 303 |
| Overall Study | Lost to Follow-up | 9 |
| Overall Study | Other, Not Specified | 20 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Rovalpituzumab Tesirine |
|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 9.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 272 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 57 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 56 Participants |
| Race (NIH/OMB) White | 265 Participants |
| Sex: Female, Male Female | 169 Participants |
| Sex: Female, Male Male | 170 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 303 / 339 |
| other Total, other adverse events | 322 / 339 |
| serious Total, serious adverse events | 178 / 339 |
Outcome results
Primary
Objective Response Rate
Objective response is defined as a participant with the best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, prior to receiving any subsequent anticancer therapy and retreatment, and is confirmed by a consecutive response assessment at least 4 weeks (28 days) from the initial determination of CR/PR. Analyzed based on response assessments from both the Independent Review Committee (IRC) and investigators. CR: disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Population: Modified Intent to Treat Population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Objective Response Rate | IRC | 15.5 percentage of participants |
| Rovalpituzumab Tesirine: DLL3 High | Objective Response Rate | Investigator | 19.3 percentage of participants |
| Rovalpituzumab Tesirine: DLL3 Positive | Objective Response Rate | IRC | 14.6 percentage of participants |
| Rovalpituzumab Tesirine: DLL3 Positive | Objective Response Rate | Investigator | 18.8 percentage of participants |
Primary
Overall Survival
Overall survival is defined as the time from the first dose date to death for any reason. Participants who were alive at the clinical data cut-off were censored at the last known alive date. Based on Kaplan-Meier estimates.
Time frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Population: Modified Intent to Treat Population: all participants who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Overall Survival | 5.3 months |
| Rovalpituzumab Tesirine: DLL3 Positive | Overall Survival | 5.3 months |
Secondary
Clinical Benefit Rate
Clinical benefit rate is defined as the percentage of participants with an overall response of CR or PR or stable disease (SD) with SD of a minimum duration of 42 days from the first dose date. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.)
Time frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Population: Modified Intent to Treat Population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Clinical Benefit Rate | IRC | 73.9 percentage of participants |
| Rovalpituzumab Tesirine: DLL3 High | Clinical Benefit Rate | Investigator | 71.0 percentage of participants |
| Rovalpituzumab Tesirine: DLL3 Positive | Clinical Benefit Rate | IRC | 72.1 percentage of participants |
| Rovalpituzumab Tesirine: DLL3 Positive | Clinical Benefit Rate | Investigator | 68.6 percentage of participants |
Secondary
Duration of Clinical Benefit
Duration of clinical benefit is defined as time from the date of first documented CR or PR or SD of ≥ 42 days from first dose date (-7 days to allow for scheduled visit window per the protocol) to the documented date PD or death, whichever occurs first. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Population: Modified Intent to Treat Population: all participants who received any amount of study drug with best overall response of CR or PR or SD.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Duration of Clinical Benefit | IRC | 2.9 months |
| Rovalpituzumab Tesirine: DLL3 High | Duration of Clinical Benefit | Investigator | 3.0 months |
| Rovalpituzumab Tesirine: DLL3 Positive | Duration of Clinical Benefit | IRC | 2.9 months |
| Rovalpituzumab Tesirine: DLL3 Positive | Duration of Clinical Benefit | Investigator | 3.0 months |
Secondary
Duration of Objective Response
Duration of objective response is defined as the time from the date of first documented CR or PR of participants with a confirmed response to the documented date of progressive disease (PD) or death, whichever occurred first. Participants who neither progressed nor died are censored at the last evaluable disease assessment. Analyzed based on response assessments from both the IRC and investigators. Based on Kaplan-Meier estimates. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.)
Time frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Population: Modified Intent to Treat Population: all participants who received any amount of study drug and had an objective response.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Duration of Objective Response | IRC | 4.0 months |
| Rovalpituzumab Tesirine: DLL3 High | Duration of Objective Response | Investigator | 4.0 months |
| Rovalpituzumab Tesirine: DLL3 Positive | Duration of Objective Response | IRC | 4.1 months |
| Rovalpituzumab Tesirine: DLL3 Positive | Duration of Objective Response | Investigator | 4.0 months |
Secondary
Number of Anti-Therapeutic Antibody (ATA) Positive Participants
Time frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Population: All participants who received rovalpituzumab tesirine and had at least one sample screened for ATA against rovalpituzumab tesirine antibody-drug conjugate concentration.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Number of Anti-Therapeutic Antibody (ATA) Positive Participants | Positive at Any Study Visit | 11 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Anti-Therapeutic Antibody (ATA) Positive Participants | Positive After First Dose of Study Drug | 3 Participants |
Secondary
Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment
TEAEs were defined as AEs that were newly occurring or worsened following study treatment.
Time frame: From first dose of study drug through the end of the initial treatment period (84 ± 6 days)
Population: Safety analysis population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Any TEAE | 335 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Thrombocytopenia | 83 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Constipation | 75 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Fatigue | 129 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Photosensitivity Reaction | 123 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Pleural effusion | 113 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Oedema peripheral | 105 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Decreased appetite | 102 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Nausea | 88 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Dyspnoea | 83 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Vomiting | 59 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Anaemia | 58 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Cough | 54 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Hypoalbuminaemia | 52 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Pericardial effusion | 50 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Abdominal pain | 50 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Asthenia | 50 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment | Diarrhoea | 47 Participants |
Secondary
Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment
An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: is fatal or life-threatening; results in death or hospitalization; is disabling/incapacitating or a congenital anomaly/birth defect; is medically significant. AE severity was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03 terminology: grade 1=mild; grade 2=moderate; grade 3=severe; grade 4 life-threatening; grade 5=death. TEAEs were defined as AEs that were newly occurring or worsened following study treatment.
Time frame: From first dose of study drug through the end of the initial treatment period (84 ± 6 days)
Population: Safety analysis population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment | Fatal AE | 34 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment | Any TEAE | 335 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment | Treatment Emergent SAE | 171 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment | TEAE Maximum Severity Grade 3/4 | 179 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment | TEAE Leading to Drug WIthdrawal | 25 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment | TEAE Leading to Dose Interruption | 33 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment | TEAE Leading to Dose Reduction | 32 Participants |
| Rovalpituzumab Tesirine: DLL3 High | Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment | TEAE Reasonably Possibly Related to Study Drug | 308 Participants |
Secondary
Overall Response Rate
Overall response rate is defined as the percentage of participants with a response of CR or PR, regardless of confirmation, per RECIST v 1.1 prior to receiving any subsequent anticancer therapy and retreatment. Any participants not exhibiting a response (CR or PR) as defined above were considered non-responders. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Population: Modified Intent to Treat Population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Overall Response Rate | IRC | 23.1 percentage of participants |
| Rovalpituzumab Tesirine: DLL3 High | Overall Response Rate | Investigator | 26.9 percentage of participants |
| Rovalpituzumab Tesirine: DLL3 Positive | Overall Response Rate | IRC | 22.0 percentage of participants |
| Rovalpituzumab Tesirine: DLL3 Positive | Overall Response Rate | Investigator | 25.8 percentage of participants |
Secondary
Progression-Free Survival
Progression-free survival is defined as the time from the first dose date to the documented date of PD or death, whichever occurred first. Participants who neither progressed nor died were censored at the last evaluable disease assessment. Analyzed based on response assessments from both the IRC and investigators. Based on Kaplan-Meier estimates. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.)
Time frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Population: Modified Intent to Treat Population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Progression-Free Survival | IRC | 3.8 months |
| Rovalpituzumab Tesirine: DLL3 High | Progression-Free Survival | Investigator | 3.9 months |
| Rovalpituzumab Tesirine: DLL3 Positive | Progression-Free Survival | IRC | 3.8 months |
| Rovalpituzumab Tesirine: DLL3 Positive | Progression-Free Survival | Investigator | 3.9 months |
Secondary
Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit
Time frame: Cycle 1: Day 1, 30 minutes pre-infusion; Day 1, 30 minutes post-infusion; Day 3; Day 15; Day 29. Cycle 2: Day 1, 30 minutes pre-infusion; Day 1, 30 minutes post-infusion; Day 3; Day 15; Day 29; End of Treatment (up to Day 29).
Population: Pharmacokinetic Analysis Population: all participants who receive at least 1 dose of study treatment and at least 1 post-baseline blood sample following a dose of study treatment and had an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 3 | 4791.1 ng/mL | Standard Deviation 1373.7 |
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 29 | 816.3 ng/mL | Standard Deviation 379.15 |
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 1, 30 minutes pre-infusion | 180.9 ng/mL | Standard Deviation 1215.03 |
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 1, 30 minutes post-infusion | 7535.6 ng/mL | Standard Deviation 1928.74 |
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 1, 30 minutes pre-infusion | 532.2 ng/mL | Standard Deviation 592.9 |
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 3 | 4535.2 ng/mL | Standard Deviation 1398.49 |
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 29 | 1029.3 ng/mL | Standard Deviation 362.28 |
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | End of Treatment | 558.5 ng/mL | Standard Deviation 296.09 |
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 15 | 1845.5 ng/mL | Standard Deviation 688.47 |
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 15 | 1472.8 ng/mL | Standard Deviation 573.9 |
| Rovalpituzumab Tesirine: DLL3 High | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 1, 30 minutes post-infusion | 7611.6 ng/mL | Standard Deviation 1980.49 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 1, 30 minutes pre-infusion | 518.6 ng/mL | Standard Deviation 226.45 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 1, 30 minutes pre-infusion | 236.6 ng/mL | Standard Deviation 923.44 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 1, 30 minutes post-infusion | 6365.5 ng/mL | Standard Deviation 1763.08 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 3 | 3740.5 ng/mL | Standard Deviation 1454.87 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 15 | 1323.3 ng/mL | Standard Deviation 504.33 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 29 | 793.8 ng/mL | Standard Deviation 322.9 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 1, 30 minutes post-infusion | 6602.7 ng/mL | Standard Deviation 1508.23 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 3 | 4670.8 ng/mL | Standard Deviation 1539.65 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 15 | 1857.7 ng/mL | Standard Deviation 599.65 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 29 | 1077.7 ng/mL | Standard Deviation 362.33 |
| Rovalpituzumab Tesirine: DLL3 Positive | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | End of Treatment | 686.9 ng/mL | Standard Deviation 354.68 |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 29 | 1300.0 ng/mL | — |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 3 | 3840.0 ng/mL | — |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 3 | 4630.0 ng/mL | Standard Deviation 1866.76 |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 1, 30 minutes pre-infusion | 148.2 ng/mL | Standard Deviation 81.81 |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 15 | 2030.0 ng/mL | — |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 1, 30 minutes post-infusion | 6690.0 ng/mL | Standard Deviation 2050.61 |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 1, 30 minutes pre-infusion | 601.0 ng/mL | — |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 29 | 956.5 ng/mL | Standard Deviation 61.52 |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | End of Treatment | 679.5 ng/mL | Standard Deviation 64.35 |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 2: Day 1, 30 minutes post-infusion | 7880.0 ng/mL | — |
| Rovalpituzumab Tesirine: Re-Treatment 2 | Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit | Cycle 1: Day 15 | 1390.0 ng/mL | Standard Deviation 381.84 |