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

July 1, 2020 updated by: AbbVie

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Avignon, France, 84082
        • Institut Sainte Catherine /ID# 165172
      • Brest Cedex, France, 29609
        • CHRU de Brest - Hospital Morva /ID# 165170
      • Marseille, France, 13005
        • Hopital La Timone /ID# 165171
    • Doubs
      • Besancon, Doubs, France, 25000
        • CHU de Besancon - Jean Minjoz /ID# 165173
    • Hauts-de-France
      • Lille, Hauts-de-France, France, 59020
        • Centre Oscar Lambret /ID# 165169
    • Val-de-Marne
      • Villejuif, Val-de-Marne, France, 94800
        • Institut Gustave Roussy /ID# 165168
  • Germany
      • Gauting, Germany, 82131
        • Asklepios Fachkliniken M. Gaut /ID# 165183
      • Grosshansdorf, Germany, 22927
        • Lungen Clinic Grosshansdorf /ID# 165182
      • Immenhausen, Germany, 34376
        • Lungenfachklinik Immenhausen /ID# 165181
    • Sachsen-Anhalt
      • Halle (Saale), Sachsen-Anhalt, Germany, 06120
        • KH Martha-Maria Halle Dolau /ID# 165180
  • Italy
      • Aviano, Italy, 33081
        • Centro di Riferimento Oncologi /ID# 165174
      • Catania, Italy, 95123
        • Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele /ID# 165178
      • Milan, Italy, 20141
        • Istituto Europeo di Oncologia /ID# 165175
      • Modena, Italy, 41100
        • AO Univ di Modena /ID# 165177
    • Milano
      • Rozzano, Milano, Italy, 20089
        • Istituto Clinico Humanitas /ID# 165176
  • Spain
      • Barcelona, Spain, 08028
        • Hosp Univ Quiron Dexues /ID# 165166
      • Madrid, Spain, 28007
        • Hospital Genl Gregorio Maranon /ID# 165162
      • Madrid, Spain, 28040
        • Hospital Universitario Fundacion Jimenez Diaz /ID# 165164
      • Madrid, Spain, 28050
        • Hospital Universitario Madrid /ID# 165163
    • Navarra, Comunidad
      • Pamplona, Navarra, Comunidad, Spain, 31008
        • Clinica Universitar de Navarra - Pamplona /ID# 165165
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Ucsd /Id# 161030
    • Florida
      • Orlando, Florida, United States, 32803
        • Florida Hospital /ID# 161017
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Cancer & Blood Cent /ID# 161028
    • Illinois
      • Chicago, Illinois, United States, 60637-1443
        • University of Chicago /ID# 161006
    • Kansas
      • Fairway, Kansas, United States, 66205
        • The University of Kansas Clini /ID# 162915
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University-School of Medicine /ID# 161011
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of NJ /ID# 161032
    • New York
      • New York, New York, United States, 10065-6007
        • Memorial Sloan Kettering Cancer Center /ID# 161010
    • North Carolina
      • Durham, North Carolina, United States, 27710-3000
        • Duke University Medical Center /ID# 161009
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University /ID# 161029
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina /ID# 161007
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC /ID# 161012
      • Nashville, Tennessee, United States, 37232-6307
        • Vanderbilt University Med Ctr /ID# 162916
    • Virginia
      • Richmond, Virginia, United States, 23230
        • Virginia Cancer Institute /ID# 161025
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • University of Wisconsin Clinic /ID# 161013

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • Opdivo®
Drug: Rovalpituzumab tesirine
Administered by intravenous infusion
Other Names:
  • 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: Nivolumab
Administered by intravenous infusion
Other Names:
  • Opdivo®
Drug: Rovalpituzumab tesirine
Administered by intravenous infusion
Other Names:
  • SC16LD6.5
Drug: Ipilimumab
Administered by intravenous infusion
Other Names:
  • Yervoy®
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: Nivolumab
Administered by intravenous infusion
Other Names:
  • Opdivo®
Drug: Rovalpituzumab tesirine
Administered by intravenous infusion
Other Names:
  • SC16LD6.5
Drug: Ipilimumab
Administered by intravenous infusion
Other Names:
  • Yervoy®

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Up to 12 weeks
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.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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)
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.
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)
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.
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)
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AbbVie

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bristol-Myers Squibb

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 30, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 3, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 3, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 18, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 18, 2017

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 20, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 17, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 1, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • M16-300
  • 2016-003686-26 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Time Frame

Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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