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 3

Recruiting

• Conditions: Limited-stage Small Cell Lung Cancer (LS-SCLC)
• Interventions: Drug: Tifcemalimab injection; Drug: Placebo for Tifcemalimab; Drug: toripalimab injection; Drug: Placebo for toripalimab

• Registration Number: NCT06095583
• Lead Sponsor: Shanghai Junshi Bioscience Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-09
• Study First Submitted QC: 2023-10-18
• Study First Posted: 2023-10-23
• Study Start: 2023-11-15
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-19
• Last Update Posted: 2024-06-21
• Primary Completion: 2027-07-31
• Study Completion: 2029-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 756

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group B	Placebo for Tifcemalimab	Placebo for tifcemalimab (IV) and toripalimab (240 mg IV)
Placebo group C	Placebo for Tifcemalimab	Placebos for both tifcemalimab and toripalimab (IV)
Experimental group A	toripalimab injection	Tifcemalimab (200 mg intravenous infusion \[IV\]) and toripalimab (240 mg IV)
Experimental group B	toripalimab injection	Placebo for tifcemalimab (IV) and toripalimab (240 mg IV)
Placebo group C	Placebo for toripalimab	Placebos for both tifcemalimab and toripalimab (IV)
Experimental group A	Tifcemalimab injection	Tifcemalimab (200 mg intravenous infusion \[IV\]) and toripalimab (240 mg IV)

Primary Outcome Measures

Name	Time	Method
OS	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"
Overall survival (OS)	up to 3years	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
Progression-free survival (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

Name	Time	Method
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 as measured by 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 as measured by ORR
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 as measured by DoR
1-year OS rate	up to 1year	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
objective response rate (ORR)	up to 2 years	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
2-year OS rate	up to 2 years	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
disease control rate (DCR)	up to 2 years	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
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 as measured by 1-year OS rate
duration of response (DoR)	up to 2years	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
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
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 as measured by DCR
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 (Percentage of participants with treatment-related adverse events as assessed by CTCAEv5.0.) and abnormal laboratory parameters.

Trial Locations

Locations (155)

Banner MD Anderson Cancer Center; 🇺🇸 Goodyear, Arizona, United States

Banner University Medical Center; 🇺🇸 Tucson, Arizona, United States

Genesis Cancer and Blood Institute (Hot Springs, AR); 🇺🇸 Hot Springs, Arkansas, United States

SCRI Nashville; 🇺🇸 Davis, California, United States

Zangmeister Cancer Center (Columbus, OH); 🇺🇸 Los Angeles, California, United States

Los Angeles Hematology Oncology; 🇺🇸 Los Angeles, California, United States

University of Southern California Norris Comprehensive Cancer; 🇺🇸 Los Angeles, California, United States

Florida Cancer Specialists Pan Handle; 🇺🇸 Fort Myers, Florida, United States

Florida Cancer Specialists South; 🇺🇸 Fort Myers, Florida, United States

USA029 University of Miami Sylvester Comprehensive Cancer Center 1550 NW 10th Avenue 33173 Miami FL Ikpeazu Chukwuemeka N; 🇺🇸 Miami, Florida, United States

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