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.
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.
Primary outcome:
1. Overall survival (OS) (Time Frame - 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
2. 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"
3. Progression-free survival (PFS) (Time Frame - 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 Blinded Independent Review Committee (BIRC)-assessed PFS.
4. Progression-free survival (PFS) (Time Frame - 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:
1. PFS (Time Frame - 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 Investigator-assessed PFS
2. 1-year OS rate (Time Frame - 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
3. 2-year OS rate (Time Frame - 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
4. objective response rate (ORR) (Time Frame - 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
5. disease control rate (DCR) (Time Frame - 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
6. duration of response (DoR) (Time Frame - 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
7. PFS (Time Frame - 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
8. 1 year OS rate (Time Frame - 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
9. 2 year OS rate (Time Frame - 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
10. ORR (Time Frame - 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
11. DCR (Time Frame - 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
12. DoR (Time Frame - 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
13. safety (Time Frame - up to 2 years):
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.
14. safety (Time Frame - 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.
- Experimental: Experimental group A
Tifcemalimab (200 mg intravenous infusion [IV]) and toripalimab (240 mg IV) - Experimental: Experimental group B
Placebo for tifcemalimab (IV) and toripalimab (240 mg IV) - Placebo Comparator: Placebo group C
Placebos for both tifcemalimab and toripalimab (IV)
- Tifcemalimab injection:
200mg once every 3weeks - toripalimab injection:
240mg once every 3 weeks - Placebo for Tifcemalimab:
every 3weeks - Placebo for toripalimab:
every 3weeks
Quelle: ClinicalTrials.gov
