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

Overview

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.

Interventions

• Drug Tifcemalimab injection
  200mg once every 3weeks
• Drug toripalimab injection
  240mg once every 3 weeks
• Drug Placebo for Tifcemalimab
  every 3weeks
• Drug Placebo for toripalimab
  every 3weeks

Primary outcome measures

• Overall survival (OS) [Time frame: up to 3years]
• OS [Time frame: up to 3years]
• Progression-free survival (PFS) [Time frame: up to 2years]
• Progression-free survival (PFS) [Time frame: up to 2years]

Secondary outcome measures (12)

• PFS [Time frame: up to 2years]
• 1-year OS rate [Time frame: up to 1year]
• 2-year OS rate [Time frame: up to 2 years]
• objective response rate (ORR) [Time frame: up to 2 years]
• disease control rate (DCR) [Time frame: up to 2 years]
• duration of response (DoR) [Time frame: up to 2years]
• PFS [Time frame: up to 2 years]
• 1 year OS rate [Time frame: up to 1 years]
• 2 year OS rate [Time frame: up to 2 years]
• ORR [Time frame: up to 2 years]
• DCR [Time frame: up to 2 years]
• DoR [Time frame: up to 2 years]

Eligibility criteria

Inclusion criteria

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

• Male or female with age ≥ 18 years old at the time of informed consent.
• 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.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1 .
• Adequate organ function
• Female patients of childbearing potential and male patients whose partners are women of childbearing age.
• 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.

• Mixed SCLC and non-small cell lung cancer (NSCLC).
• Received sequential chemoradiotherapy for LS-SCLC.
• 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.
• Patients with active autoimmune disease, history of autoimmune disease.
• History of immunodeficiency, including HIV seropositivity, other acquired congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation.
• History of confirmed or suspected interstitial lung disease or pneumonitis (except for Grade 1 radiation pneumonitis not treated with corticosteroids).
• 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).
• 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.
• Women who are pregnant or breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 31 centers

• Harbin Medical University Cancer Hospital — Harbin
• Xiangya Hospital Central South University — Changsha
• The Second Affiliated Hospital of Nanchang University — Nanchang
• The First Hospital of China Medical University — Shenyang
• Shandong Cancer Hospital & Institute — Jinan
• Anyang Tumor Hospital — Anyang
• Beijing Cancer Hospital — Beijing
• Cancer Hospital Chinese Academy of Medical Sciences — Beijing
• … and 23 more centers

Turkey (Türkiye) · 13 centers

• Ankara City Hospital — Ankara
• Ankara Liv Hospital — Ankara
• Gulhane Training and Research Hospital - Medical Oncology — Ankara
• Memorial Ankara Hospital — Ankara
• Trakya University Medical Faculty — Edirne
• Bakirköy Dr. Sadi Konuk Eğitim ve Araştirma Hastanesi - Oncology — Istanbul
• Istanbul Goztepe Prof. Dr. Suleyman Yalcin City Hospital - Medical Oncology — Istanbul
• Ege University Medical Faculty - Pulmonary — Izmir
• … and 5 more centers

Taiwan · 11 centers

• Taipei Veterans General Hospital — Taipei City
• No.123,DAPI Rd. Niaosong Dist, Kaohsiung City 83301 Taiwan, R.O.C. — Kaohsiung City
• China Medical University Hospital - Internal Medicine - Taichung — Taichung
• Taichung Veterans General Hospital — Taichung
• Chi Mei Hospital, Liouying - Department of Oncology — Tainan
• National Cheng Kung University Hospital — Tainan
• National Taiwan University Hospital - Internal Medicine — Taipei
• Taipei Medical University - Shuang Ho Hospital — Taipei
• … and 3 more centers

Spain · 9 centers

• Complexo Hospitalario Universitario A Coruña — A Coruña
• Hospital Universitari Dexeus Grupo Quironsalud — Barcelona
• Complejo Hospitalario de Jaén — Jaén
• Fundacion Jimenez Diaz — Madrid
• Hospital Clínico San Carlos — Madrid
• Hospital Universitario La Paz — Madrid
• Hospital Universitario Donostia — San Sebastián
• H.C.U.Lozano Blesa — Zaragoza
• … and 1 more center

Georgia · 8 centers

• ISR-GEO Med Res Clin Healthycore — Tbilisi
• Ltd New Hospitals — Tbilisi
• Multprofil Clinic Consilium Medulla — Tbilisi
• Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic — Tbilisi
• "TIM - Tbilisi Institute of Medicine" LTD — Tbilisi
• ICO-Institute of Clinical Oncology - Hospital — Tbilisi
• LTD "Israel-Georgian Medical Research Clinic Healthycore" — Tbilisi
• LTD "New Hospitals" — Tbilisi

Netherlands · 4 centers

• Jeroen Bosch Ziekenhuis — 's-Hertogenbosch
• Rijnstate Ziekenhuis — Arnhem
• Erasmus Medisch Centrum — Rotterdam
• Isala Klinieken Zwolle — Zwolle

Identifiers

NCT: NCT06095583 · JS004-008-III-SCLC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗