IRB Study Number HLX10-005-SCLC301-E
Status Recruiting
Location Mercy Hospital
Institute Taussig Cancer Institute
Description
Primary Objectives
To compare the efficacy of HLX10 plus chemotherapy versus atezolizumab plus chemotherapy in US patients with previously untreated ES-SCLC.
Secondary Objectives
To evaluate the efficacy of HLX10 plus chemotherapy in US patients with previously untreated ES-SCLC.
To evaluate the clinical safety, the pharmacokinetics and immunogenicity of HLX10 in combination with chemotherapy in US patients with previously untreated ES-SCLC.
Inclusion Criteria
Voluntary participation in clinical studies; fully understand, be informed about the study and have signed the informed consent form (ICF); willingness to follow and ability to complete all trial procedures.
Male or female aged ≥ 18 years at the time of signing the ICF.
Histologically or cytologically diagnosed with ES-SCLC (according to the Veterans Administration Lung Study Group staging system).
No prior systemic therapy for ES-SCLC (including systemic chemotherapy, molecular targeted therapy, biological therapy, and other investigational therapies, etc.). Note that for some patients that may have received first cycle of chemotherapy for newly diagnosed ES-SCLC as continued treatment, such patients are permitted.
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.
At least one measurable lesion as assessed according to RECIST 1.1 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.
Every effort should be made to provide tumor tissues for the determination of PD-L1 expression. Note: It is recommended to provide formalin-fixed tumor tissue samples, paraffinembedded 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 Fine-needle aspirations, freshly collected specimens, radical resections, core needle biopsy, excisions, incisions, punch or clamp biopsies are acceptable. For detailed requirements for tissue samples, see the laboratory manual.
Prior antineoplastic therapy including Chinese medicine therapy, which has been approved as antineoplastic therapy by NMPA or its instruction has antineoplastic therapy effect, 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).
An ECOG PS score of 0 or 1.
An expected survival ≥ 12 weeks.
Subjects with prior denosumab use that can and agree to switch to bisphosphonate therapy for bone metastases starting prior to randomization and throughout treatment.
Normal major organ functions as defined by the following criteria (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):
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. Of child-bearing potential, but must meet the following:
○ Serum pregnancy test must be negative within 7 days prior to randomization, and
○ Agree to use birth control methods with an annual failure rate of <1% or maintain abstinence (avoid heterosexual intercourse) (from the signing of ICF to at least 6 months after the final dose of study drug) (birth control methods with an annual failure rate of <1% include bilateral tubal ligation, male sterilization, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine contraceptive devices and copper-containing intrauterine contraceptive devices or condoms), and
○ Must not be breast-feeding.
- Male patients must: agree to abstinence (avoid heterosexual intercourse) or take contraception measures as follows: male patients with a pregnant partner or a partner of childbearing potential must remain abstinent or use a condom or had vasectomy to prevent embryonic exposure during study treatment and for at least 6 months after the last dose of study drug. Periodic abstinence (e.g., contraceptive methods based on calendar day, ovulation, basal body temperature or post-ovulation) and external ejaculation are ineligible methods of contraception.
Exclusion Criteria
Histologically or cytologically confirmed mixed SCLC.
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.
Patients who are preparing for or have received an organ or bone marrow transplant.
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters are allowed regardless of drainage frequency.
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 weeks (as confirmed by 1 radiological examination 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.).
Subjects with spinal cord compression that has not been treated with surgery and/or radiotherapy.
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).
Class III to IV cardiac insufficiency according to NYHA classification.
Subject has uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN).
Subject with peripheral neuropathy ≥ Grade 2 by CTCAE.
Human immunodeficiency virus (HIV) infection, positive test for HIV antibody.
Active or latent pulmonary tuberculosis.
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.
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 coinfection (positive test for HBsAg or HBcAb and positive test for HCV antibody).
Known active or suspected autoimmune diseases. Subjects in a stable state with no need for systemic immunosuppressant therapy are allowed to enroll.
Have received treatment with live vaccines within 28 days prior to the first administration. Subjects may receive inactivated viral vaccines for seasonal influenza but may not receive live attenuated influenza vaccines via intranasal route.
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 inhaled steroids and adrenal hormone replacement therapy at doses equivalent to ≤ 10 mg/day of prednisone efficacy.
With any active infection requiring systemic anti-infective treatment at the time of first dose of study treatment.
Major surgery within 28 days prior to the first dose of the study drug, defined as: surgeries requiring at least 3 weeks of recovery to be able to receive treatment in this study.
Radical radiation therapy within 3 months prior to study medications. Note: Palliative radiotherapy to bone or palliative radiotherapy to superficial lesions is allowed according to local standards 14 days prior to the first dose. Radiotherapy covering more than 30% of the bone marrow area within 28 days prior to the first dose is not allowed.
The subject has previously received other antibodies/drugs against immune checkpoints, such as PD-1, PD-L1, CTLA4, etc.
Participation in any other ongoing clinical studies, or less than 14 days from the end of the previous clinical study treatment to the start of this trial.
Known history of severe allergy to any monoclonal antibody.
Known hypersensitivity to carboplatin or etoposide.
Pregnant or lactating women.
Active use of psychotropics abuse or drug abuse.
In the judgment of the investigator, the subject has any other factors that may lead to a premature discontinuation.
