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)

Phase 3RecruitingNCT06095583

Shanghai Junshi Bioscience Co., Ltd.756 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

756

Conditions

Limited-stage Small Cell Lung Cancer (LS-SCLC)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (76)

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, China

RECRUITING

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, China

Outcomes

Primary Outcomes

Overall survival (OS)

To compare and evaluate the efficacy of tifcemalimab and toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after chemoradiotherapy (CRT) for patients with LS-SCLC as measured by OS

Time frame: up to 3years

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"

Time frame: up to 3years

Progression-free survival (PFS)

To compare and evaluate the efficacy of tifcemalimab and toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by Blinded Independent Review Committee (BIRC)-assessed PFS.

Time frame: up to 2years

Progression-free survival (PFS)

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.

Time frame: up to 2years

Secondary Outcomes

PFS

To compare and evaluate the efficacy of tifcemalimab and toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by Investigator-assessed PFS

Time frame: up to 2years

1-year OS rate

To compare and evaluate the efficacy of tifcemalimab and toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by 1-year OS rate

Time frame: up to 1year

2-year OS rate

To compare and evaluate the efficacy of tifcemalimab and toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by 2-year OS rate

Time frame: up to 2 years

objective response rate (ORR)

To compare and evaluate the efficacy of tifcemalimab and toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by ORR

Time frame: up to 2 years

disease control rate (DCR)

To compare and evaluate the efficacy of tifcemalimab and toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by DCR

Time frame: up to 2 years

duration of response (DoR)

To compare and evaluate the efficacy of tifcemalimab and toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by DoR

Time frame: up to 2years

PFS

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

Time frame: up to 2 years

1 year OS rate

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 1-year OS rate

Time frame: up to 1 years

2 year OS rate

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 2-year OS rate

Time frame: up to 2 years

ORR

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 ORR

Time frame: up to 2 years

DCR

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 DCR

Time frame: up to 2 years

DoR

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 DoR

Time frame: up to 2 years

Safety（adverse events and abnormal laboratory parameters）

To compare and evaluate the safety of tifcemalimab and 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 (Percentage of participants with treatment-related adverse events as assessed by CTCAEv5.0.) and abnormal laboratory parameters.

Time frame: up to 2 years

Safety（adverse events and abnormal laboratory parameters）

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 (Percentage of participants with treatment-related adverse events as assessed by CTCAEv5.0.) and abnormal laboratory parameters.

Time frame: up to 2 years

Central Contacts

kui zhang, Project Directer

CONTACT

08618168028925 kui_zhang@junshipharma.com

Kinga Kovacs, Senior Project Leader

CONTACT

+ 31 6 45974346 Kinga.Kovacs@parexel.com