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)

Shanghai Junshi Biosciences

Status and phase: Enrolling; Phase 3

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

Treatments: Drug: Tifcemalimab injection; Drug: Placebo for Tifcemalimab; Drug: Placebo for toripalimab; Drug: toripalimab injection

Study type: Interventional

Funder types: Other

Identifiers

NCT06095583

JS004-008-III-SCLC

Details and patient eligibility

About

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.

Enrollment: 756 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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756 participants in 3 patient groups, including a placebo group

Experimental group A

Experimental group

Description:

Tifcemalimab (200 mg intravenous infusion \[IV\]) and toripalimab (240 mg IV)

Treatment:

Drug: toripalimab injection

Drug: Tifcemalimab injection

Experimental group B

Experimental group

Description:

Placebo for tifcemalimab (IV) and toripalimab (240 mg IV)

Treatment:

Drug: toripalimab injection

Drug: Placebo for Tifcemalimab

Placebo group C

Placebo Comparator group

Description:

Placebos for both tifcemalimab and toripalimab (IV)

Treatment:

Drug: Placebo for toripalimab

Drug: Placebo for Tifcemalimab