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

Small Cell Lung Cancer Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03026166
• Other study ID #: M16-300
• Secondary ID: 2016-003686-26
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 30, 2017
• Est. completion date: July 3, 2019

Study information

• Verified date: July 2020
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. completion date: July 3, 2019
• Est. primary completion date: July 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• Ipilimumab
Administered by intravenous infusion
• Nivolumab
Administered by intravenous infusion
• Rovalpituzumab tesirine
Administered by intravenous infusion

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.