A Phase III, Open-Label Study of Maintenance Lurbinectedin in Combination With Atezolizumab Compared With Atezolizumab in Participants With Extensive-Stage Small-Cell Lung Cancer

Small-Cell Lung Cancer Clinical Trial

— IMforte  

Official title:

A Phase III, Randomized, Open-Label, Multicenter Study of Lurbinectedin in Combination With Atezolizumab Compared With Atezolizumab as Maintenance Therapy in Participants With Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) Following First-Line Induction Therapy With Carboplatin, Etoposide and Atezolizumab

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05091567
• Other study ID #: GO43104
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 18, 2021
• Est. completion date: March 6, 2026

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study GO43104 is a Phase III, randomized, open-label, multicenter study of lurbinectedin in combination with atezolizumab compared with atezolizumab alone administered as maintenance therapy in participants with extensive-stage small-cell lung cancer (ES-SCLC) after first-line induction therapy with carboplatin, etoposide, and atezolizumab. The study consists of 2 phases: an induction phase and a maintenance phase. Participants need to have an ongoing response or stable disease per the Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 criteria after completion of 4 cycles of carboplatin, etoposide, and atezolizumab induction treatment in order to be considered for eligibility screening for the maintenance phase. Eligible participants will be randomized in a 1:1 ratio to receive either lurbinectedin plus atezolizumab or atezolizumab in the maintenance phase.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 690
• Est. completion date: March 6, 2026
• Est. primary completion date: April 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria for the Induction Phase:

• ECOG PS of 0 or 1
• No prior systemic therapy for ES-SCLC
• Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC
• Histologically or cytologically confirmed ES-SCLC
• Adequate hematologic and end-organ function to receive 4 cycles of induction treatment with carboplatin, etoposide and atezolizumab
• Measurable disease, as defined by RECIST v1.1
• Negative HIV test and no evidence of active Hepatitis B or Hepatitis C at screening

Exclusion Criteria for the Induction Phase:

• Presence or history of CNS metastases
• Active or history of autoimmune disease or deficiency
• History of malignancies other than SCLC within 5 years prior to enrollment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, or lurbinectedin or trabectedin
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Treatment with investigational therapy within 28 days prior to enrollment

Inclusion Criteria for the Maintenance Phase:

• ECOG PS of 0 or 1
• Ongoing response or stable disease per RECIST 1.1 after 4 cycles of induction therapy
• Toxicities attributed to prior induction anti-cancer therapy or PCI resolved to Grade <=1
• Adequate hematologic and end-organ function

Exclusion Criteria for the Maintenance Phase:

• Presence or history of CNS metastases
• Receiving consolidative chest radiation
• Severe infection within 2 weeks prior to randomization into the maintenance
• Treatment with therapeutic oral or IV antibiotics at the time of randomization

Related Conditions & MeSH terms

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

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle for 4 cycles in the induction phase. Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle in the maintenance phase.
• Lurbinectedin
Lurbinectedin 3.2 mg/m² will be administered intravenously on Day 1 of each 21-day cycle in the maintenance phase.
• Carboplatin
Carboplatin will be administered according to the standard of care treatment for 4 cycles in the induction phase.
• Etoposide
Etoposide will be administered according to the standard of care treatment for 4 cycles in the induction phase.

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Anderlecht
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	AZ St Maarten Campus Leopoldstr	Mechelen
Belgium	CHU UCL Mont-Godinne	Mont-godinne
Belgium	Vitaz	Sint Niklaas
Germany	Zentralklinik Bad Berka GmbH; Abteilung Onkologie und Hämatologie	Bad Berka
Germany	Evang. Lungenklinik Berlin Klinik für Pneumologie	Berlin
Germany	Helios Klinikum Emil von Behring GmbH	Berlin
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	KEM/Evang. Kliniken Essen Mitte gGmbH; Klinik für Internistische Onkologie / Hämatologie	Essen
Germany	Asklepios Klinik Gauting; Onkologisches Studienzentrum	Gauting
Germany	Niels-Stensen-Kliniken Franziskus-Hospital Harderberg GmbH	Georgsmarienhütte
Germany	LungenClinic Großhansdorf GmbH; Klinische Forschung	Großhansdorf
Germany	Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II	Halle
Germany	KRH Klinikum Siloah-Oststadt-Heidehaus	Hannover
Germany	Fachklinik für Lungenerkrankungen	Immenhausen
Germany	Universitätsklinikum Schleswig-Holstein; Campus Lübeck	Lübeck
Germany	Krankenhaus Barmherziger Brüder; Klinik für Internistische Onkologie / Hämatologie	Regensburg
Greece	ERRIKOS DYNAN HOSPITAL; 4th ONCOLOGY CLINIC	Athens
Greece	Sotiria Thoracic Diseases Hospital of Athens; 3rd University Pathology Clinic	Athens
Greece	University Hospital of Larissa;Department of Medical Oncology	Larissa
Greece	Diavalkaniko Hospital	Thessaloniki
Greece	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki
Hungary	Orszagos Koranyi Pulmonologiai Intezet	Budapest
Hungary	Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet	Pécs
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rend.Int.	Szolnok
Hungary	Tudogyogyintezet Torokbalint	Torokbalint
Italy	ASL 3 Genovese	Genova	Liguria
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck	Milano	Lombardia
Italy	Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia	Milano	Lombardia
Italy	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia
Italy	AUSL della Romagna; Dipartimento Oncoematologico - U.O.C. Oncologia	Ravenna	Emilia-Romagna
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti	Torrette Di Ancona	Marche
Korea, Republic of	Chungbuk National University Hospital	Cheongju si
Korea, Republic of	Chilgok Kyungpook National University Medical Center	Daegu
Korea, Republic of	Gyeongsang National University Hospital	Gyeongsangnam-do
Korea, Republic of	Samsung Changwon Hospital	Gyeongsangnam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Ulsan University Hosiptal	Ulsan
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara	Jalisco
Mexico	Filios Alta Medicina	Monterrey	Nuevo LEON
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii	Gdansk
Poland	Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II; Oddzia? Onkologiczny	Kraków
Poland	Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii	Olsztyn
Poland	Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy; Oddzial III Chorob Pluc	Otwock
Poland	Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu; Oddzial Onkologii Klinicznej	Poznan
Poland	Centrum Onkologii Instytut im.Marii Sklodowskiej-Curie; Klinika Nowotworow Pluca i Klatki Piersiowej	Warszawa
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Sant Andreu de La Barca	Barcelona
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Taiwan	E-DA Hospital; Chest	Kaohsiung
Taiwan	Taichung Veterans General Hospital; Dept of Internal Medicine	Taichung
Taiwan	National Cheng Kung University Hospital; Oncology	Tainan
Taiwan	Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology	Taipei
Turkey	Adana Baskent University Hospital; Medical Oncology	Adana
Turkey	Ankara City Hospital; Oncology	Ankara
Turkey	Gülhane E?itim Ve Ara?t?rma Hastanesi	Ankara
Turkey	Liv Hospital Ankara; Medical Oncology	Ankara
Turkey	Memorial Ankara Hastanesi	Ankara
Turkey	Uludag Uni Hospital; Oncology	Bursa
Turkey	Pamukkale University School Of Medicine; Oncology Department	Denizli
Turkey	Dicle University Faculty of Medicine	Diyarbakir
Turkey	Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi	Edirne
Turkey	Ba?c?lar Medipol Mega Üniversite Hastanesi; Oncology	Istanbul
Turkey	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul
Turkey	?zmir Medical Park; Onkoloji	Izmir
Turkey	Kocaeli University Faculty of Medicine; Medical oncology	Izmit
Turkey	Goztepe Prof.Dr. Suleyman Yalcin City Hospital; Clinical Oncology	Kadiköy
Turkey	Medikal Park Samsun	Samsun
Turkey	TC Necmettin Erbakan University Meram Medical Faculty Hospital	Selçuklu
Turkey	Ac?badem Altunizade Hastanesi; Oncology	Üsküdar
United Kingdom	Ysbyty Gwynedd Hospital	Bangor
United Kingdom	Blackpool Victoria Hospital	Blackpool
United Kingdom	Western General Hospital; Edinburgh Cancer Center	Edinburgh
United Kingdom	Christie NHS Foundation Trust	GB Manchester
United Kingdom	Castle Hill Hospital; The Queen's Centre for Oncology & Haematology	Hull
United Kingdom	St James University Hospital	Leeds
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Guy's Hospital; Oncology & Haematology Clinical Trials (OHCT) Unit. GI/Urology Research Office	London
United Kingdom	University College London Hospital	London
United States	Hematology Oncology Clinic	Baton Rouge	Louisiana
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Hollings Cancer Center	Charleston	South Carolina
United States	Greco-Hainesworth Centers for Research; ETN (East Tennessee)	Chattanooga	Tennessee
United States	The Mark H. Zangmeister Ctr; Mid Ohio Onc/Hem Inc.	Columbus	Ohio
United States	National Jewish Health	Denver	Colorado
United States	Florida Cancer Specialists - Fort Myers (Broadway)	Fort Myers	Florida
United States	West Clinic	Germantown	Tennessee
United States	Cancer & Hematology Centers of Western Michigan; Spectrum Health Butterworth Research Pharmacy	Grand Rapids	Michigan
United States	Michael E. DeBakey VA Medical Center	Houston	Texas
United States	Optum Health Care	Las Vegas	Nevada
United States	Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital	Marietta	Georgia
United States	Tennessee Oncology; Sarah Cannon Research Institute	Nashville	Tennessee
United States	Illinois Cancer Care	Peoria	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mercy Research - St. Louis	Saint Louis	Missouri
United States	Florida Cancer Specialist, North Region	Saint Petersburg	Florida
United States	Mays Cancer Center at UT Health San Antonio MD Anderson Cancer	San Antonio	Texas
United States	New England Cancer Specialists	Scarborough	Maine
United States	Mercy Research SPRG	Springfield	Missouri
United States	SCRI Florida Cancer Specialists PAN	Tallahassee	Florida
United States	Florida Cancer Specialists	West Palm Beach	Florida
United States	Clinical Research Alliance	Westbury	New York

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Jazz Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Greece,  Hungary,  Italy,  Korea, Republic of,  Mexico,  Poland,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IRF-Assessed Progression-Free Survival (PFS)	IRF-assessed progression-free survival (PFS) is defined as the time from randomization to the date of first documented disease progression (as assessed by the IRF according to RECIST v1.1), or death whichever occurs first.	Randomization to the date of first documented disease progression or death, whichever occurs first (up to approximately 60 months)
Primary	Overall Survival (OS)	Overall survival (OS) is defined as the time from randomization to the date of death from any cause.	Randomization to the date of death from any cause (up to approximately 60 months)
Secondary	Investigator-Assessed PFS	Investigator-assessed PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first).	Randomization to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 60 months)
Secondary	Confirmed Objective Response Rate (ORR) as Determined by the IRF	Confirmed objective response rate (ORR) is defined as the proportion of randomized participants with a CR or PR on two consecutive occasions >= 4 weeks apart after randomization, as determined by the IRF according to RECIST v1.1.	Up to approximately 60 months
Secondary	Confirmed Objective Response Rate (ORR) as Determined by the Investigator	Confirmed objective response rate (ORR) is defined as the proportion of randomized participants with a CR or PR on two consecutive occasions >= 4 weeks apart after randomization, as determined by the Investigator according to RECIST v1.1.	Up to approximately 60 months
Secondary	Duration of Response (DOR) as Determined by the IRF	Duration of Response (DOR) (for participants with a confirmed objective response) is defined as the time from the first occurrence of a documented confirmed objective response after randomization until disease progression as determined by the IRF according to RECIST v1.1, or death from any cause, whichever occurs first.	Up to approximately 60 months
Secondary	Duration of Response (DOR) as Determined by the Investigator	Duration of Response (DOR) (for participants with a confirmed objective response) is defined as the time from the first occurrence of a documented confirmed objective response after randomization until disease progression as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first.	Up to approximately 60 months
Secondary	PFS Rates as Determined by the IRF	PFS rates at 6 months and 12 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months and 12 months after randomization, as determined by the IRF according to RECIST v1.1.	6 months and 12 months after randomization
Secondary	PFS Rates as Determined by the Investigator	PFS rates at 6 months and 12 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months and 12 months after randomization, as determined by the investigator according to RECIST v1.1.	6 months and 12 months after randomization
Secondary	OS Rates	OS rates at 12 months and 24 months is defined as the proportion of participants who have not experienced death from any cause at 12 months and 24 months after randomization.	12 months and 24 months after randomization
Secondary	Percentage of Participants With Adverse Events	Percentage of participants with adverse events.	Up to approximately 60 months
Secondary	Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab	Percentage of participants with ADAs to atezolizumab after drug administration.	Up to approximately 60 months
Secondary	Time to Confirmed Deterioration (TTCD)	Time to confirmed deterioration (TTCD) from randomization in participant-reported physical functioning and global health status as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30).	Up to approximately 60 months