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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
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
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AbbVie

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Drug: Ipilimumab Drug: Nivolumab Drug: Rovalpituzumab tesirine Phase 1 Phase 2

Detailed Description:

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.

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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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

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

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




Primary Outcome Measures :
  1. 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

  2. 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.



Secondary Outcome Measures :
  1. 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.


  2. 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.


  3. 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.


  4. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Locations
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Sponsors and Collaborators
AbbVie
Bristol-Myers Squibb
Investigators
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Study Director: AbbVie Inc. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
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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

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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
Keywords provided by AbbVie:
Cancer
Extensive-Stage Small Cell Lung Cancer
Nivolumab
Ipilimumab
Rovalpituzumab tesirine
Additional relevant MeSH terms:
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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