A Study of Rovalpituzumab Tesirine Administered in Combination With Nivolumab and With or Without Ipilimumab for Adults With Extensive-Stage Small Cell Lung Cancer

Browse trials for

• Lung Neoplasms 7,243
• Small Cell Lung Carcinoma 1,203

Keywords

• Cancer
• Extensive-Stage Small Cell Lung Cancer
• Nivolumab
• Ipilimumab
• Rovalpituzumab tesirine

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 42 is below the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.

Lead sponsor

AbbVie is the lead sponsor of 953 studies on the registry; 136 are open to participants now.

Of its 350 completed or terminated interventional studies of FDA-regulated products, 210 (60%) have results posted.

Study arms

• Experimental
  Rovalpituzumab Tesirine and Nivolumab

  Participants will receive 2 doses of 0.3 mg/kg rovalpituzumab tesirine by intravenous (IV) infusion 6 weeks apart (Day 1 of Cycles 1 and 3), and 2 doses of 360 mg nivolumab IV 3 weeks apart beginning on Cycle 2 (Day 1 of Cycles 2 and 3). Participants will then receive maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 4 until disease progression.

  Drug: Nivolumab · Drug: Rovalpituzumab tesirine

• Experimental
  Rovalpituzumab Tesirine and Nivolumab + Ipilimumab 1 mg/kg

  Participants will receive 2 doses of 0.3 mg/kg rovalpituzumab tesirine IV 6 weeks apart (Day 1 of Cycles 1 and 3), nivolumab 1 mg/kg every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5), and ipilimumab 1 mg/kg IV every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5). After a 6-week washout, participants will then receive maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 6 until disease progression.

  Drug: Ipilimumab · Drug: Nivolumab · Drug: Rovalpituzumab tesirine

• Experimental
  Rovalpituzumab Tesirine and Nivolumab + Ipilimumab 3 mg/kg

  Participants will receive 2 doses of 0.3 mg/kg rovalpituzumab tesirine IV 6 weeks apart (Day 1 of Cycles 1 and 3), nivolumab 1 mg/kg every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5), and ipilimumab 3 mg/kg IV every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5). After an 8-week washout, participants will then receive maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 6 until disease progression.

  Drug: Ipilimumab · Drug: Nivolumab · Drug: Rovalpituzumab tesirine

Interventions

• DrugIpilimumab

  Administered by intravenous infusion

  Also known as: Yervoy®

• DrugNivolumab

  Administered by intravenous infusion

  Also known as: Opdivo®

• DrugRovalpituzumab tesirine

  Administered by intravenous infusion

  Also known as: SC16LD6.5

Primary outcomes

1. 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

2. 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.

Secondary outcomes

1. Objective Response Rate (ORR)

   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.

2. 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.

3. 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.

4. 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.

Baseline characteristics

Study documents

• Protocol and statistical analysis plan · Dec 1, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

Supporting information: Study protocol, Sap, Csr, Analytic code