Clinical trial NCT06095583: Phase 3 Study of Toripalimab Alone or in Combination With Tifcemalimab as Consolidation Therapy in Patients With Limited-stage Small Cell Lung Cancer (LS-SCLC)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Regional Phase III Clinical Study of Toripalimab Alone or in Combination With Tifcemalimab (JS004/TAB004) as Consolidation Therapy in Patients With Limited-Stage Small Cell Lung Cancer Without Disease Progression Following Chemoradiotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Limited-stage Small Cell Lung Cancer (LS-SCLC)
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
First posted: 2023-10-23
Enrollment: 756
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Study is a Phase 3, randomized, three-arm, double-blind, placebo-controlled, multi-regional clinical research study to evaluate the safety and efficacy use of toripalimab alone or in combination with tifcemalimab as consolidation therapy in patients with limited-stage small cell lung cancer without disease progression following chemoradiotherapy.

Tifcemalimab is a monoclonal antibody against B and T lymphocyte attenuator (BTLA). Toripalimab is a monoclonal antibody against programmed death protein-1 (PD-1). Neither drug is approved for treatment of This combination regimen is investigational in limited stage-small cell lung cancer in any country.


Eligibility criteria: Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be enrolled:

1. Male or female with age ≥ 18 years old at the time of informed consent.
2. Histologically or cytologically confirmed LS-SCLC using the Veteran's Administration Lung Study Arm (VALSG) staging criteria (Appendix 3). Patients with TNM Stage I or II disease per AJCC 8th edition must be medically inoperable (as determined by the Investigator) or the patient must refuse surgery.
3. Received CRT defined as: (1) 4 cycles of chemotherapy consisting of carboplatin or cisplatin and intravenously administered etoposide; (2) a total radiation dose of 60-66 Gy for the standard once daily (QD) radiotherapy regimen or 45 Gy for the hyperfractionated twice daily (BID) radiotherapy regimen; (3) Patients must begin investigational interventions within 42 days of the last dose of chemotherapy.
4. Patients must have achieved a complete response (CR), partial response (PR), or stable disease (SD) after receiving curative platinum-based CRT and must not have developed progressive disease (PD) prior to study entry.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1 .
6. Adequate organ function
7. Female patients of childbearing potential and male patients whose partners are women of childbearing age.
8. Voluntarily agree to participate in the study, sign the informed consent form, and agree to comply with all study and follow-up procedures.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria.

1. Mixed SCLC and non-small cell lung cancer (NSCLC).
2. Received sequential chemoradiotherapy for LS-SCLC.
3. Failure to recover from toxicity of prior anticancer therapy to Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 (except alopecia) or levels specified in the inclusion/exclusion criteria, whichever is more severe.
4. Patients with active autoimmune disease, history of autoimmune disease.
5. History of immunodeficiency, including HIV seropositivity, other acquired congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation.
6. History of confirmed or suspected interstitial lung disease or pneumonitis (except for Grade 1 radiation pneumonitis not treated with corticosteroids).
7. The presence of active hepatitis B (HBV DNA ≥ 500 IU/mL), hepatitis C (hepatitis C antibodies positive and HCV-RNA higher than the lower limit of detection of the analytical method).
8. Any other malignancy diagnosed prior to the first dose of investigational intervention, except those with a low risk for the development of metastases (5-year survival rate \> 90%), such as adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or breast, or adequately treated localized prostate cancer.
9. Women who are pregnant or breastfeeding.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: up to 3years
measure: OS
timeFrame: up to 3years
measure: Progression-free survival (PFS)
timeFrame: up to 2years
measure: Progression-free survival (PFS)
timeFrame: up to 2years
Secondary outcomes:
measure: PFS
timeFrame: up to 2years
measure: 1-year OS rate
timeFrame: up to 1year
measure: 2-year OS rate
timeFrame: up to 2 years
measure: objective response rate (ORR)
timeFrame: up to 2 years
measure: disease control rate (DCR)
timeFrame: up to 2 years
measure: duration of response (DoR)
timeFrame: up to 2years
measure: PFS
timeFrame: up to 2 years
measure: 1 year OS rate
timeFrame: up to 1 years
measure: 2 year OS rate
timeFrame: up to 2 years
measure: ORR
timeFrame: up to 2 years
measure: DCR
timeFrame: up to 2 years
measure: DoR
timeFrame: up to 2 years
measure: safety
timeFrame: up to 2 years
measure: safety
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center
state: Arizona
city: Hot Springs
country: United States
facility: Genesis Cancer and Blood Institute (Hot Springs, AR)
state: Arkansas
city: Davis
country: United States
facility: SCRI Nashville
state: California
city: Los Angeles
country: United States
facility: Zangmeister Cancer Center (Columbus, OH)
state: California
city: Los Angeles
country: United States
facility: Los Angeles Hematology Oncology
state: California
city: Los Angeles
country: United States
facility: University of Southern California Norris Comprehensive Cancer
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists Pan Handle
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists South
state: Florida
city: Miami
country: United States
facility: USA029 University of Miami Sylvester Comprehensive Cancer Center 1550 NW 10th Avenue 33173 Miami FL Ikpeazu Chukwuemeka N
state: Florida
city: Orange City
country: United States
facility: Mid-Florida Hematology Oncology
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital
state: Georgia
city: Louisville
country: United States
facility: Norton Cancer Institute, Downtown, Multidisciplinary Clinic
state: Kentucky
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland, PA
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute-Hematology/Oncology
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of Western Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: North Shore Hematology Oncology Associates DBA NY Cancer and Blood Specialists
state: New York
city: Stony Brook
country: United States
facility: University of Stony Brook
state: New York
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center - Toledo
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates Of Oregon, P.C.
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Houston
country: United States
facility: Millennium Physicians - Oncology
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. - Oncology
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Antwerpen
country: Belgium
facility: Algemeen Ziekenhuis Klina
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi - Site Notre-Dame
city: Kortrijk
country: Belgium
facility: AZ Groeningen
city: Limbourg
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse
city: Namur
country: Belgium
facility: CHU UCL Namur - Site Sainte-Elisabeth
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital & Institute
state: Shandong
city: Anyang
country: China
facility: Anyang Tumor Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Chengdu
country: China
facility: Sichuan cancer hospital
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Guangdong
country: China
facility: Peking University Shenzhen Hospital
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
city: Hangzhou
country: China
facility: No. 1 Bandong Road, Gongshu District, Hangzhou
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
city: Hefei
country: China
facility: The First Affiliated Hospital of Ustc
city: Henan
country: China
facility: Henan Cancer Hospital
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shenyang
country: China
facility: Liaoning cancer hospital
city: Taiyuan
country: China
facility: Shanxi Cancer hospital
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Wuhan
country: China
facility: Hubei Cancer Hospital (Hubei Cancer Research Institute)
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
city: Angers
country: France
facility: Centre Hospitalier Universitaire D Angers
city: Bordeaux
country: France
facility: Institut Bergonie
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal De Créteil
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lyon
country: France
facility: Centre Leon Berard - departement d'oncologie medicale
city: Montpellier
country: France
facility: Centre de Cancérologie du Grand Montpellier
city: Montpellier
country: France
facility: Hopital Arnaud De Villeneuve - Oncologie/Pneumologie
city: Pessac
country: France
facility: Hopital Haut-Leveque - Maladies respiratoires
city: Rouen
country: France
facility: Chu Hôpitaux De Rouen
city: Saint-Herblain
country: France
facility: Institut de Cancérologie de l'Ouest (ICO)
city: Tours Cedex 9
country: France
facility: Chru De Tours
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Tbilisi
country: Georgia
facility: "TIM - Tbilisi Institute of Medicine" LTD
city: Tbilisi
country: Georgia
facility: ICO-Institute of Clinical Oncology - Hospital
city: Tbilisi
country: Georgia
facility: ISR-GEO Med Res Clin Healthycore
city: Tbilisi
country: Georgia
facility: LTD "Israel-Georgian Medical Research Clinic Healthycore"
city: Tbilisi
country: Georgia
facility: LTD "New Hospitals"
city: Tbilisi
country: Georgia
facility: Ltd New Hospitals
city: Tbilisi
country: Georgia
facility: Multprofil Clinic Consilium Medulla
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Esslingen
country: Germany
facility: Klinikum Esslingen GmbH Klinik für Kardiologie, Angiolgie und Pneumolgoie
city: Gießen
country: Germany
facility: Univeristätsklinikum Giessen und Marburg GmbH
city: Kassel
country: Germany
facility: Klinikum Kassel GmbH Klinik für Onkologie uind Hämatologie- Onkologisches Studiensekretariat
city: Münster
country: Germany
facility: Gemeinschaftspraxis fuer Haematologie und Onkologie
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Catania
country: Italy
facility: PO G. Rodolico, AOU Policlinico-Vittorio Emanuele Catania
city: Cesena
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori IRCCS
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena, Policlinico di Mod
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli
city: Padova
country: Italy
facility: Iov, Irccs
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo, Università degli studi di Pavia
city: Roma
country: Italy
facility: AO S. Camillo-Forlanini
city: Roma
country: Italy
facility: Regina Elena, Istituto Nazionale dei Tumori, IFO, IRCCS Feasibility survey: PO di Livorno, AUSL Toscana Nord Ovest, SST
city: Cheonju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Herzogenbusch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Zwolle
country: Netherlands
facility: Isala Klinieken Zwolle
city: Białystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
city: Olsztyn
country: Poland
facility: SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii
city: Poznań
country: Poland
facility: Wielkopolskie Centrum Pulmonologii i Torakochirurgii im. E. i J. Zeylandow
city: Warszawa
country: Poland
facility: Instytut Gruzlicy i Chorob Pluc
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca
city: Cluj-Napoca
country: Romania
facility: Medisprof
city: Craiova
country: Romania
facility: Centrul de Oncologie Sf. Nectarie
city: Craiova
country: Romania
facility: Oncolab
city: Floreşti
country: Romania
facility: Radiotherapy Center Cluj
city: Timişoara
country: Romania
facility: Oncomed
city: Barcelona
country: Spain
facility: Hospital Universitari Dexeus Grupo Quironsalud
city: Castellón De La Plana
country: Spain
facility: C.H. Provincial de Castellón
city: Coruña
country: Spain
facility: Centro Oncológico de Galicia
city: Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Orense
country: Spain
facility: Complejo Hospitalario Universitario de Orense
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen De La Macarena
city: Valencia
country: Spain
facility: Hospital Arnau De Vilanova De Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Y Politécnico La Fe
city: Zaragoza
country: Spain
facility: H.C.U.Lozano Blesa
city: Taipei city
country: Taiwan
facility: Taipei Veterans General Hospital
state: Taipei
city: Kaohsiung
country: Taiwan
facility: No.123,DAPI Rd. Niaosong Dist, Kaohsiung City 83301 Taiwan, R.O.C.
city: Taichung
country: Taiwan
facility: China Medical University Hospital - Internal Medicine - Taichung
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan City
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Hospital, Liouying - Department of Oncology
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital - Internal Medicine
city: Taipei
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University - Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University - WanFang Hospital - Hematology and Oncology
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Ankara
country: Turkey
facility: Ankara Liv Hospital
city: Ankara
country: Turkey
facility: Gulhane Training and Research Hospital - Medical Oncology
city: Ankara
country: Turkey
facility: Memorial Ankara Hospital
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty
city: Istanbul
country: Turkey
facility: Bakirköy Dr. Sadi Konuk Eğitim ve Araştirma Hastanesi - Oncology
city: Istanbul
country: Turkey
facility: Istanbul Goztepe Prof. Dr. Suleyman Yalcin City Hospital - Medical Oncology
city: İzmir
country: Turkey
facility: Ege University Medical Faculty - Pulmonary
city: İzmir
country: Turkey
facility: İzmir Ekonomi Üniversitesi Medical Point İzmir Hastanesi
city: İzmir
country: Turkey
facility: Katip Celebi University Ataturk Research and Training Hospit
city: Kocaeli
country: Turkey
facility: Kocaeli University Research and Practice Hospital
city: Konya
country: Turkey
facility: Necmettin Erbakan University Meram
city: Malatya
country: Turkey
facility: Inonu University Turgut Ozal Medical Center
Study officials:
References: