Extensive Stage Small Cell Lung Cancer (ES-SCLC) MedDRA version: 21.1 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection
Product Code: HLX10
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Serplulimab
Current Spon
Sponsors
Shanghai Henlius Biotech, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Voluntary participation in clinical studies; fully understand, be informed about the study and have signed the ICF; willingness to follow and ability to complete all trial procedures. 2. Male or female aged = 18 years at the time of signing the ICF. 3. Histologically or cytologically diagnosed with ES-SCLC (according to the Veterans Administration Lung Study Group staging system). 4. No prior systemic therapy for ES-SCLC (including systemic chemotherapy, molecular targeted therapy, biological therapy, and other investigational therapies, etc.). 5. Patients who have received chemoradiotherapy for previous limited stage SCLC must be treated with curative intent and have a treatment-free interval of at least 6 months from the last course of chemotherapy, radiotherapy, or chemoradiotherapy to the diagnosis of extensive stage SCLC. 6. At least one measurable lesion as assessed by the IRRC according to RECIST v1.1 within 4 weeks prior to randomization. Note: Measurable lesions are not from previously irradiated sites. If the lesion at the previously irradiated site is the only selectable target lesion, a radiological assessment showing significant progression of the irradiated lesion should be provided by the investigator. 7. Patients must provide tumor tissues that meet the requirements for the determination of PD-L1 expression levels. Patients are assessed for an evaluable PD-L1 expression category (negative: TPS <1%, positive: TPS =1%, or not evaluable/not available) by the central laboratory for randomization. Note: It is recommended to provide formalin-fixed tumor tissue samples, paraffin-embedded tumor specimens (preferred), formalin-fixed paraffin embedded (FFPE), tumor specimens or newly prepared unstained serial tissue sections (preferably adhesive slides) within 6 months prior to the first dose of study medication. A relevant pathology report must also be provided for the above specimens. Freshly collected specimens, radical resections, core needle biopsy, excisions, incisions, punch or clamp biopsies are acceptable (newly obtained tissues are preferred). Fine-needle aspirations (i.e., samples that lack a complete tissue structure and provide only cell suspension and/or cell smear), brush biopsies, and cell pellet samples from pleural or peritoneal effusions are unacceptable. For detailed requirements for tissue samples, see the laboratory manual. 8. Prior antineoplastic therapy must have been = 2 weeks from the first dose in this study with treatment-related AEs resolved to NCI-CTCAE Grade = 1 (except for Grade 2 alopecia). 9. An ECOG PS score of 0 or 1 10. An expected survival = 12 weeks 11. Subjects with prior denosumab use that can and agree to switch to bisphosphonate therapy for bone metastases starting prior to randomization and throughout treatment. 12. Normal major organ functions as defined by the criteria listed in the protocol (no blood transfusions, or treatment with albumin, recombinant human thrombopoietin or colony-stimulating factor within 14 days prior to the first dose in this study). 13. Female patients must meet one of the following conditions: a. Menopause (defined as no menses for at least 1 year and no confirmed cause other than menopause), or b. Surgically sterilized (removal of the ovaries and/or uterus), or c. With child-bearing potential, but must meet the following: - Serum pregnancy test must be negati
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. Histologically or cytologically confirmed mixed SCLC. 2. Other active malignancies within 5 years or at the same time. Localized tumors that have been cured, such as basal cell carcinoma, squamous-cell skin cancer, superficial bladder cancer, prostate carcinoma in situ, cervical cancer in situ and breast cancer in situ are acceptable. 3. Patients who are preparing for or have received an organ or bone marrow transplant. 4. Pleural or pericardial effusion requiring clinical intervention, or ascites. 5. Patients with known or documented active CNS metastases and/or carcinomatous meningitis at screening. However, the following subjects are allowed to be enrolled: 1) Subjects with asymptomatic brain metastases (i.e., no progressive central nervous system symptoms caused by brain metastases, no requirement for corticosteroids, and lesion size = 1.5 cm) may be included, but are required to receive regular brain imaging as a site of lesion. 2) Subjects with treated brain metastases which have been stable for at least 2 months (as confirmed by 2 radiological examinations at least 4 weeks apart after treatment of brain metastases), with no evidence of new or enlarging brain metastases, and with discontinued steroids 3 days prior to study drug administration. (Stable brain metastases here should be confirmed before the first dose of the study drug.). 6. Subjects with spinal cord compression that has not been radically treated with surgery and/or radiotherapy. 7. Patients with myocardial infarction within half a year before the first dose of the study drug, poorly controlled arrhythmia (including QTc intervals = 450 ms for males and = 470 ms for females) (QTc intervals are calculated by Fridericia's formula). 8. Class III to IV cardiac insufficiency according to NYHA classification or a left ventricular ejection fraction 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN). 10. Subject with peripheral neuropathy = Grade 2 by CTCAE. 11. Human immunodeficiency virus (HIV) infection, positive test for HIV antibody. 12. Active or latent pulmonary tuberculosis. 13. Subjects with previous and concurrent interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis and severe impaired pulmonary function that may interfere with the detection and management of suspected drug-related pulmonary toxicity as judged by the investigator. 14. Hepatitis B (positive test for HBsAg or HBcAb and positive test for HBV-DNA) or Hepatitis C (positive tests for HCV antibody and HCV-RNA). Hepatitis B and C co-infection (positive test for HBsAg or HBcAb and positive test for HCV antibody). 15. Known active or suspected autoimmune diseases. Subjects in a stable state with no need for systemic immunosuppressant therapy are allowed to enroll. 16. Treatment with live vaccines and all COVID-19 vaccines (fully administered to the required number of doses) within 28 days prior to study drug administration; inactivated viral vaccines for seasonal influenza are allowed. 17. Subjects requiring treatment with systemic corticosteroids (> 10 mg/day prednisone efficacy dose) or other immunosuppressive drugs within 14 days prior to the first dose or during the study. However, in the absence of active autoimmune disease, subjects are allowed to use topical or i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the clinical efficacy of HLX10 in combination with chemotherapy versus placebo in combination with chemotherapy in previously untreated patients with ES-SCLC.;Secondary Objective: - To compare the safety and tolerability of HLX10 in combination with chemotherapy versus placebo in combination with chemotherapy in previously untreated patients with ES SCLC and evaluate pharmacokinetics (PK), immunogenicity, and biomarkers. ;Primary end point(s): Primary Efficacy Endpoint • Overall survival (OS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints • Progression-free survival (PFS) (assessed by the independent radiology review committee [IRRC] based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) • PFS (assessed by the investigator based on RECIST 1.1 and a modified RECIST 1.1 for immune-based therapeutics [termed iRECIST]) • PFS2 (assessed by the investigator based on RECIST 1.1) • Objective response rate (ORR) (assessed by the IRRC and investigator based on RECIST 1.1) • Duration of response (DOR) (assessed by the IRRC and the investigator based on RECIST 1.1) Safety Endpoints • Adverse events (AEs) (including serious adverse events [SAEs]), laboratory tests (routine blood test, blood chemistry, coagulation function, urinalysis, myocardial function and thyroid function), 12-lead electrocardiogram (12 lead ECG), vital signs, and physical examination, etc. Pharmacokinetic (PK) Endpoint • Concentration of HLX10 in serum Immunogenicity Endpoint • HLX10 anti-drug antibody (ADA) positive rate Biomarker Endpoint • Relationship between PD-L1 expression, microsatellite instability (MSI), tumor mutation burden (TMB) in tumor tissue and efficacy. Quality of life assessment ;Timepoint(s) of evaluation of this end point: · OS – occur around 3.5 years after FPI · PFS – As assessed by the investigator based on RECIST 1.1, at screening (within 4 weeks pre-dose), every 6 weeks (± 7 days) during the first 48 weeks after the start of study treatment, and every 9 weeks (± 7 days) after week 48. · ORR – As assessed by the IRRC and investigator based on RECIST 1.1 · DOR – As assessed by the IRRC and investigator based on RECIST 1.1 · AEs - As assessed by the investigator during visit or informed by subject PK and ADA - Sample will be collected at the following time points: within 7 days pre-dose in Cycle 1, within 3 days pre-dose in Cycles 2, 4, 6, 8 and every 4 cycles thereafter, within 2 hours after the end of dosing in Cycles 1 and 8 of treatment peri | — |
Countries
Bulgaria, China, Georgia, Poland, Russian Federation, Türkiye, Ukraine, United States
Contacts
Public ContactClinical Development
Shanghai Henlius Biotech, Inc.
Outcome results
None listed