A Study to Assess Toripalimab Alone or in Combination With Tifcemalimab as Consolidation Therapy in Patients With Limited-stage Small Cell Lung Cancer (LS-SCLC)
Study Details
Study Description
Brief Summary
The Study is a Phase 3, randomized, double-blind, placebo-controlled, multi-regional clinical research study to evaluate the 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). This combination regimen is investigational in small cell lung cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental group A Tifcemalimab (200 mg intravenous infusion [IV]) combined with toripalimab (240 mg IV) |
Drug: Tifcemalimab injection
200mg once per 3weeks
Drug: toripalimab injection
240mg once per 3 weeks
|
| Experimental: Experimental group B Placebo for tifcemalimab (IV) combined with toripalimab (240 mg IV) |
Drug: toripalimab injection
240mg once per 3 weeks
Drug: Placebo for Tifcemalimab
per 3weeks
|
| Placebo Comparator: Placebo group C Placebos for both tifcemalimab and toripalimab (IV) |
Drug: Placebo for Tifcemalimab
per 3weeks
Drug: Placebo for toripalimab
per 3weeks
|
Outcome Measures
Primary Outcome Measures
- OS [up to 3years]
To compare and evaluate the efficacy of tifcemalimab combined with toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after chemoradiotherapy (CRT) for patients with LS-SCLC as measured by overall survival (OS)
- OS [up to 3years]
Estimand for the primary objective "to compare and evaluate the efficacy of toripalimab (Arm B) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by OS"
- PFS [up to 2years]
To compare and evaluate the efficacy of tifcemalimab combined with toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after chemoradiotherapy (CRT) for patients with LS-SCLC as measured by Blinded Independent Review Committee (BIRC)-assessed progression-free survival (PFS).
- PFS [up to 2years]
To compare and evaluate the efficacy of toripalimab (Arm B) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by OS and BIRC-assessed PFS.
Secondary Outcome Measures
- PFS [up to 2years]
To compare and evaluate the efficacy of tifcemalimab combined with toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by Investigator-assessed PFS
- 1-year OS rate [up to 1year]
To compare and evaluate the efficacy of tifcemalimab combined with toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC 1year OS
- 2-year OS rate [up to 2 years]
To compare and evaluate the efficacy of tifcemalimab combined with toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC 2year OS
- objective response rate (ORR) [up to 2 years]
To compare and evaluate the efficacy of tifcemalimab combined with toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC ORR
- disease control rate (DCR) [up to 2 years]
To compare and evaluate the efficacy of tifcemalimab combined with toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC DCR
- duration of response (DoR) [up to 2years]
To compare and evaluate the efficacy of tifcemalimab combined with toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC DoR
- PFS [up to 2 years]
To compare and evaluate the efficacy of toripalimab (Arm B) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLS as measured by Investigator-assessed PFS
- 1 year OS rate [up to 1 years]
To compare and evaluate the efficacy of toripalimab (Arm B) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLS 1 year OS rate
- 2 year OS rate [up to 2 years]
To compare and evaluate the efficacy of toripalimab (Arm B) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLS 2 year OS rate
- ORR [up to 2 years]
To compare and evaluate the efficacy of toripalimab (Arm B) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLS ORR
- DCR [up to 2 years]
To compare and evaluate the efficacy of toripalimab (Arm B) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLS 2 year DCR
- DoR [up to 2 years]
To compare and evaluate the efficacy of toripalimab (Arm B) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLS 2 year DoR
- safety [up to 2 years]
To compare and evaluate the safety of tifcemalimab combined with toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by the incidence of adverse events(Number ofparticipants with treatment-related adverse events as assessed by CTCAEv5.0.) and abnormal laboratory parameters（Laboratory values are compared numerically in the same unit of the same parameter）.
- safety [up to 2 years]
To compare and evaluate the safety of toripalimab (Arm B) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by the incidence of adverse events(Number ofparticipants with treatment-related adverse events as assessed by CTCAEv5.0.) and abnormal laboratory parameters（Laboratory values are compared numerically in the same unit of the same parameter）.
- pharmacokinetic (PK) [up to 2 years]
To characterize the pharmacokinetic (PK)/trough concentrations of tifcemalimab and toripalimab.
- immunogenicity profiles [up to 2 years]
To evaluate the immunogenicity profiles of tifcemalimab and of toripalimab and to assess the impact of immunogenicity on PK//trough concentrations, safety(Number ofparticipants with treatment-related adverse events as assessed by CTCAEv5.0.), and efficacy(PFS/OS), if data allow.
Other Outcome Measures
- correlation [up to 2 years]
To evaluate the correlation between biomarkers(PD-L1) and efficacy(OS/PFS).
Eligibility Criteria
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 achieve a complete response (CR), partial response (PR), or stable disease (SD) after receiving curative platinum-based CRT and must not have developed PD prior to study entry.
-
Eastern Cooperative Collaboration 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shandong Cancer Hospital & Institute | Jinan | Shandong | China |
Sponsors and Collaborators
- Shanghai Junshi Bioscience Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- JS004-008-III-SCLC