A Study of Rovalpituzumab Tesirine Administered in Combination With Nivolumab and With or Without Ipilimumab for Adults With Extensive-Stage Small Cell Lung Cancer
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| ClinicalTrials.gov Identifier: NCT03026166 |
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Recruitment Status :
Terminated
(Enrollment was stopped after the dose-limiting toxicity (DLT) evaluation phase of Cohort 2.)
First Posted : January 20, 2017
Results First Posted : July 1, 2020
Last Update Posted : July 17, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Small Cell Lung Cancer | Drug: Ipilimumab Drug: Nivolumab Drug: Rovalpituzumab tesirine | Phase 1 Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 42 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2 Study on the Safety of Rovalpituzumab Tesirine Administered in Combination With Nivolumab or Nivolumab and Ipilimumab for Adults With Extensive-Stage Small Cell Lung Cancer |
| Actual Study Start Date : | March 30, 2017 |
| Actual Primary Completion Date : | July 3, 2019 |
| Actual Study Completion Date : | July 3, 2019 |
| Arm | Intervention/treatment |
|---|---|
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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
Administered by intravenous infusion
Other Name: Opdivo® Drug: Rovalpituzumab tesirine Administered by intravenous infusion
Other Name: SC16LD6.5 |
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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
Administered by intravenous infusion
Other Name: Yervoy® Drug: Nivolumab Administered by intravenous infusion
Other Name: Opdivo® Drug: Rovalpituzumab tesirine Administered by intravenous infusion
Other Name: SC16LD6.5 |
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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
Administered by intravenous infusion
Other Name: Yervoy® Drug: Nivolumab Administered by intravenous infusion
Other Name: Opdivo® Drug: Rovalpituzumab tesirine Administered by intravenous infusion
Other Name: SC16LD6.5 |
- Number of Participants With Dose-limiting Toxicities (DLT) [ Time Frame: Up to 12 weeks ]
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
- Number of Participants With Adverse Events (AEs) [ 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. ]
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.
- Objective Response Rate (ORR) [ 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. ]
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.
- Duration of Response (DOR) [ 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 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.
- Progression-free Survival (PFS) [ 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. ]
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.
- Overall Survival (OS) [ 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 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Participants with histologically or cytologically confirmed extensive-stage small cell lung cancer (SCLC) with progressive disease after at least one platinum-based chemotherapeutic regimen and with evaluable or measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate hematologic, hepatic, and renal function
Exclusion Criteria:
- Has active, known, or suspected autoimmune disease
- Had prior exposure to an immuno-oncology or pyrrolobenzodiazepine (PBD)-based drug
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03026166
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| Study Director: | AbbVie Inc. | AbbVie |
| Responsible Party: | AbbVie |
| ClinicalTrials.gov Identifier: | NCT03026166 |
| Other Study ID Numbers: |
M16-300 2016-003686-26 ( EudraCT Number ) |
| First Posted: | January 20, 2017 Key Record Dates |
| Results First Posted: | July 1, 2020 |
| Last Update Posted: | July 17, 2020 |
| Last Verified: | July 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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 Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) Analytic Code |
| Time Frame: | Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. |
| Access Criteria: | Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link. |
| URL: | https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Cancer Extensive-Stage Small Cell Lung Cancer Nivolumab Ipilimumab Rovalpituzumab tesirine |
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Lung Neoplasms Small Cell Lung Carcinoma Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases |
Carcinoma, Bronchogenic Bronchial Neoplasms Nivolumab Ipilimumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |