The purpose of this study is to assess the safety and efficacy of rovalpituzumab tesirine administered in combination with nivolumab or nivolumab and ipilimumab in participants with extensive-stage small cell lung cancer (SCLC).
The study planned to enroll three cohorts with approximately 30 participants in each, including a dose-limiting toxicity (DLT) evaluation phase (the first 12 weeks of any treatment) and an expansion phase. Initially, up to 12 participants were to be enrolled into Cohort 1 in order to obtain 6 evaluable participants through the DLT evaluation period of 12 weeks. Safety data were reviewed by a Safety Monitoring Committee (SMC) for each cohort during the DLT evaluation phase before the next cohort opened. Once a new cohort was opened, the previously opened cohort was permitted to continue enrolling participants for the expansion phase for a total of 30 participants per cohort. Only two of the planned three cohorts enrolled participants in the study based on the SMC recommendation after DLTs were identified in Cohort 2.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Administered by intravenous infusion
Administered by intravenous infusion
Administered by intravenous infusion
Number of Participants With Dose-limiting Toxicities (DLT)
Dose-limiting toxicities were defined as any of the following in the 12-week DLT-evaluation period, graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03: * Grade 4 thrombocytopenia (or Grade 3 thrombocytopenia with bleeding) lasting more than 7 days and/or requiring platelet transfusion * Grade 4 neutropenia lasting more than 7 days, and/or requiring hematopoietic growth factor rescue, or any febrile neutropenia (Grade 3 or 4 neutropenia with concurrent fever ≥ 38.3°C) * Grade 4 anemia unrelated to underlying disease * Clinically significant Grade 3 or 4 non-hematologic laboratory abnormality that did not resolve to Grade 0/1 or baseline within 7 days * Grade 3 or 4 non-laboratory adverse event (AE), except fatigue, asthenia, nausea, or other manageable constitutional symptom
Time frame: Up to 12 weeks
Number of Participants With Adverse Events (AEs)
The investigator rated the severity of each AE according to the NCI CTCAE Version 4.03 and according to the following: Grade 1: The AE is transient and easily tolerated by the subject (mild). Grade 2: The AE causes the subject discomfort and interrupts the subject's usual activities (moderate). Grade 3/4: The AE causes considerable interference with the subject's usual activities and may be incapacitating or life-threatening (severe). Grade 5: The AE resulted in death of the subject (severe). The maximum severity AE for each participant is reported. A serious adverse event was defined as an AE meeting any of the following: * Death * Life-threatening * Resulted in hospitalization or prolongation of hospitalization * Resulted in congenital abnormality * Resulted in persistent or significant disability or incapacity * Was an important medical event requiring medical intervention to prevent a serious outcome. Relationship to study drug was assessed by the Investigator.
Time frame: From the first dose of study drug until 100 days after the last dose of study drug; median duration of treatment was 65 days and 53 days in each cohort respectively.
Objective Response Rate (ORR)
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Ucsd /Id# 161030
La Jolla, California, United States
Florida Hospital /ID# 161017
Orlando, Florida, United States
University Cancer & Blood Cent /ID# 161028
Athens, Georgia, United States
University of Chicago /ID# 161006
Chicago, Illinois, United States
The University of Kansas Clini /ID# 162915
Fairway, Kansas, United States
Washington University-School of Medicine /ID# 161011
St Louis, Missouri, United States
Rutgers Cancer Institute of NJ /ID# 161032
New Brunswick, New Jersey, United States
Memorial Sloan Kettering Cancer Center /ID# 161010
New York, New York, United States
Duke University Medical Center /ID# 161009
Durham, North Carolina, United States
Oregon Health and Science University /ID# 161029
Portland, Oregon, United States
...and 25 more locations
Treatment response was assessed by radiographic tumor evaluations conducted by a central radiology review. Objective response rate (ORR) is defined as the percentage of participants whose best overall response is either a confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria for Solid Tumors (RECIST) v1.1. Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. Partial response (PR): A ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR or PR must have been confirmed at least 4 weeks (28 days) from the initial determination per RECIST v 1.1.
Time frame: Cohort 1: at Week 6, Week 13, and every 8 weeks thereafter; Cohort 2: at Week 6, Week 12, Week 18, and every 8 weeks thereafter, to the end of follow-up; median duration on follow-up was 31.7 and 48.0 weeks in each cohort respectively.
Duration of Response (DOR)
Duration of overall response is defined as the time from the date of first documented CR or PR, assessed by central radiology review and based on RECIST v. 1.1, to the documented date of progressive disease (PD) or death, whichever occurred first. Participants who neither progressed nor died were censored at the last evaluable disease assessment. Duration of response was evaluated using Kaplan-Meier methodology. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, with an absolute increase of at least 0.5 cm, or the unequivocal progression of non-target lesions, or the appearance of one or more new lesions.
Time frame: Cohort 1: at Week 6, Week 13, and every 8 weeks thereafter; Cohort 2: at Week 6, Week 12, Week 18 and every 8 weeks thereafter, to the end of follow-up; median duration on follow-up was 31.7 and 48.0 weeks in each cohort respectively.
Progression-free Survival (PFS)
Progression-free survival is defined as the time from the first dose date to the documented date of PD or death, whichever occurred first, based on central radiology review according to RECIST v 1.1. Progression-free survival was evaluated using Kaplan-Meier methodology. Participants who neither progressed nor died were censored at the last evaluable disease assessment. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, with an absolute increase of at least 0.5 cm, or the unequivocal progression of non-target lesions, or the appearance of one or more new lesions.
Time frame: From first dose of study drug to the end of follow-up; median duration on follow-up was 31.7 and 48.0 weeks in each cohort respectively.
Overall Survival (OS)
Overall survival is defined as the time from the first dose date to death for any reason. Participants who were still alive were censored at the last known alive date. Overall survival was evaluated using Kaplan-Meier methodology.
Time frame: From first dose of study drug to the end of follow-up; median duration on follow-up was 31.7 and 48.0 weeks in each cohort respectively.