Clinical Trials /

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

NCT03026166

Description:

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).

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03026166

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: M16-300
  • SECONDARY ID: 2016-003686-26
  • NCT ID: NCT03026166

Conditions

  • Small Cell Lung Cancer

Interventions

DrugSynonymsArms
IpilimumabYervoy®Rovalpituzumab Tesirine and Nivolumab + Ipilimumab 1 mg/kg
NivolumabOpdivo®Rovalpituzumab Tesirine and Nivolumab
Rovalpituzumab tesirineSC16LD6.5Rovalpituzumab Tesirine and Nivolumab

Purpose

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).

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.

Trial Arms

NameTypeDescriptionInterventions
Rovalpituzumab Tesirine and NivolumabExperimentalParticipants 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.
  • Nivolumab
  • Rovalpituzumab tesirine
Rovalpituzumab Tesirine and Nivolumab + Ipilimumab 1 mg/kgExperimentalParticipants 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.
  • Ipilimumab
  • Nivolumab
  • Rovalpituzumab tesirine
Rovalpituzumab Tesirine and Nivolumab + Ipilimumab 3 mg/kgExperimentalParticipants 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.
  • Ipilimumab
  • Nivolumab
  • Rovalpituzumab tesirine

Eligibility 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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Dose-limiting Toxicities (DLT)
Time Frame:Up to 12 weeks
Safety Issue:
Description: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

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:AbbVie

Trial Keywords

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

Last Updated

July 17, 2020