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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)

Primary Purpose

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

Status
Not yet recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Tifcemalimab injection
toripalimab injection
Placebo for Tifcemalimab
Placebo for toripalimab
Sponsored by
Shanghai Junshi Bioscience Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Limited-stage Small Cell Lung Cancer (LS-SCLC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Shandong Cancer Hospital & Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Experimental group A

Experimental group B

Placebo group C

Arm Description

Tifcemalimab (200 mg intravenous infusion [IV]) combined with toripalimab (240 mg IV)

Placebo for tifcemalimab (IV) combined with toripalimab (240 mg IV)

Placebos for both tifcemalimab and toripalimab (IV)

Outcomes

Primary Outcome Measures

OS
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
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
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
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
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
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
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)
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)
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)
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
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
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
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
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
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
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
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
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)
To characterize the pharmacokinetic (PK)/trough concentrations of tifcemalimab and toripalimab.
immunogenicity profiles
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.

Full Information

First Posted
October 9, 2023
Last Updated
October 18, 2023
Sponsor
Shanghai Junshi Bioscience Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT06095583
Brief Title
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)
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 25, 2023 (Anticipated)
Primary Completion Date
July 31, 2027 (Anticipated)
Study Completion Date
July 31, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Junshi Bioscience Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Limited-stage Small Cell Lung Cancer (LS-SCLC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
756 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental group A
Arm Type
Experimental
Arm Description
Tifcemalimab (200 mg intravenous infusion [IV]) combined with toripalimab (240 mg IV)
Arm Title
Experimental group B
Arm Type
Experimental
Arm Description
Placebo for tifcemalimab (IV) combined with toripalimab (240 mg IV)
Arm Title
Placebo group C
Arm Type
Placebo Comparator
Arm Description
Placebos for both tifcemalimab and toripalimab (IV)
Intervention Type
Drug
Intervention Name(s)
Tifcemalimab injection
Intervention Description
200mg once per 3weeks
Intervention Type
Drug
Intervention Name(s)
toripalimab injection
Intervention Description
240mg once per 3 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo for Tifcemalimab
Intervention Description
per 3weeks
Intervention Type
Drug
Intervention Name(s)
Placebo for toripalimab
Intervention Description
per 3weeks
Primary Outcome Measure Information:
Title
OS
Description
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)
Time Frame
up to 3years
Title
OS
Description
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"
Time Frame
up to 3years
Title
PFS
Description
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).
Time Frame
up to 2years
Title
PFS
Description
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 Outcome Measure Information:
Title
PFS
Description
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
Time Frame
up to 2years
Title
1-year OS rate
Description
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
Time Frame
up to 1year
Title
2-year OS rate
Description
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
Time Frame
up to 2 years
Title
objective response rate (ORR)
Description
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
Time Frame
up to 2 years
Title
disease control rate (DCR)
Description
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
Time Frame
up to 2 years
Title
duration of response (DoR)
Description
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
Time Frame
up to 2years
Title
PFS
Description
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
Title
1 year OS rate
Description
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
Time Frame
up to 1 years
Title
2 year OS rate
Description
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
Time Frame
up to 2 years
Title
ORR
Description
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
Time Frame
up to 2 years
Title
DCR
Description
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
Time Frame
up to 2 years
Title
DoR
Description
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
Time Frame
up to 2 years
Title
safety
Description
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).
Time Frame
up to 2 years
Title
safety
Description
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).
Time Frame
up to 2 years
Title
pharmacokinetic (PK)
Description
To characterize the pharmacokinetic (PK)/trough concentrations of tifcemalimab and toripalimab.
Time Frame
up to 2 years
Title
immunogenicity profiles
Description
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.
Time Frame
up to 2 years
Other Pre-specified Outcome Measures:
Title
correlation
Description
To evaluate the correlation between biomarkers(PD-L1) and efficacy(OS/PFS).
Time Frame
up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
kui zhang, Project Directer
Phone
08618168028925
Email
kui_zhang@junshipharma.com
Facility Information:
Facility Name
Shandong Cancer Hospital & Institute
City
Jinan
State/Province
Shandong
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jinming Yu, MD, PhD,
Phone
86 13806406293
Email
sdyujinming@126.com
First Name & Middle Initial & Last Name & Degree
Jinming Yu, MD, PhD,

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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)

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