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

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: Terminated
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Nivolumab; Drug: Rovalpituzumab tesirine; Drug: Ipilimumab

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: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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 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

Outcome Measure	Measure Description	Time Frame
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	Up to 12 weeks
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.	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

Outcome Measure	Measure Description	Time Frame
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.	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)	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)	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)	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

• Sponsor: AbbVie
• Collaborators: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2017
• Primary Completion (Actual): July 3, 2019
• Study Completion (Actual): July 3, 2019

Study Registration Dates

• First Submitted: January 18, 2017
• First Submitted That Met QC Criteria: January 18, 2017
• First Posted (Estimate): January 20, 2017

Study Record Updates

• Last Update Posted (Actual): July 17, 2020
• Last Update Submitted That Met QC Criteria: July 1, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Cancer; Nivolumab; Ipilimumab; Rovalpituzumab tesirine; Extensive-Stage Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID 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