Golidocitinib With PD-1 Inhibitors as Maintenance Treatment for Previously Untreated ES-SCLC

Inclusion Criteria:

1. Able to provide a signed and dated informed consent form, including compliance withthe requirements and restrictions listed in the ICF and this protocol;

2. Subjects are ≥ 18 years old when signing the ICF;

3. Subjects have an ECOG performance status score of 0 or 1 and have not deterioratedin the past 2 weeks;

4. Life expectancy ≥ 3 months;

5. Histologically or cytologically confirmed ES-SCLC (stage IV [any T stage, any Nstage, M1 a/b/c stage] according to the 8th edition of the AJCC TNM staging systemfor lung cancer, or T3-4 stage disease caused by multiple lung nodules and thedisease is too diffuse, or the tumor/nodule volume is too large to be tolerated by atolerable radiotherapy plan);

6. The presence of at least one measurable lesion (based on RECIST 1.1): with a longdiameter ≥ 10 mm (lymph node lesions require a short diameter of ≥15 mm) that can beaccurately and repeatedly measured at baseline under CT or MRI; and there aremeasurable lesions outside the central nervous system;

7. SCLC patients who have not received any systemic anti-tumor treatment for advanceddisease; if the patient has received neoadjuvant/adjuvant therapy in the past, theinterval between the diagnosis of ES-SCLC and the completion of the last treatmentmust be at least 6 months;

8. Patients must be suitable for platinum (cisplatin or carboplatin)-based chemotherapyas the first-line treatment for ES-SCLC;

9. Adequate bone marrow reserve and organ system function reserve, summarized asfollows:

• Absolute neutrophil count (ANC) ≥ 1.5×109/L without growth factor support;

• Platelet ≥ 100×109/L without growth factor support or blood transfusion;

• Hemoglobin ≥ 9 g/dL or 90 g/L without erythropoietin or blood transfusion;

• Total bilirubin ≤ 1.5 × ULN; if suffering from Gilbert syndrome (unconjugatedhyperbilirubinemia), total bilirubin should be ≤ 3 × ULN;

• ALT and AST ≤ 2.5 × ULN. For patients with documented liver metastases, AST andALT levels ≤ 5 × ULN;

• Creatinine clearance calculated by the Cockcroft-Gault method, >60 ml/min forpatients receiving cisplatin and >45 ml/min for patients receiving carboplatin;

• Urine routine examination shows less than 2+ protein in urine, or 24-hour urineprotein quantitative <1 g;

• Good coagulation function, defined as international normalized ratio (INR)and/or prothrombin time (PT) ≤1.5 times ULN and/or activated partialthromboplastin time (APTT) ≤1.5 upper limit of normal; if the subject isreceiving anticoagulant therapy, as long as the PT is within the intended userange of the anticoagulant drug;

• Serum amylase ≤1.5 times ULN and/or serum lipase ≤1.5 times ULN;

• Left ventricular ejection fraction (LVEF) ≥ 55%;

10. For patients with central nervous system metastases, the following conditions mustbe met before they can be included:

• No neurological symptoms or symptoms are stable for at least 2 weeks afterlocal treatment, no need to use corticosteroids or anti-epileptic drugs, andhormonal treatment has been stopped within 3 days before the first dose ofstudy drug;

• If brain metastases have been treated locally (radiotherapy or surgery), thereshould be a time window of ≥ 2 weeks before the first dose of study treatmentto ensure that local treatment-related adverse events have been reduced toCTCAE ≤ 1 grade;

11. Women of childbearing potential must undergo a urine and/or serum pregnancy test (ifthe urine test cannot be confirmed as negative) within 7 days before the firstmedication, and the result must be negative; WOCBP or men and their WOCBP partnersshould agree to take effective contraceptive measures from the signing of the ICFuntil 6 months after the last dose of the study drug;

12. The subjects should be able to understand the study protocol and voluntarily complywith the study and follow-up;

13. For patients who are about to enter the maintenance period, the investigator shalldetermine whether they are suitable for starting treatment with golidocitinibcombined with PD-1 inhibitors (generally all previous toxicities must be alleviatedto CTCAE ≤ 1 level, excluding hair loss, fatigue or other conditions that are judgedby the investigator to be clinically insignificant).

Exclusion Criteria:

1. Histopathological confirmation of the presence of mixed NSCLC and SCLC components;

2. The presence of spinal cord compression or meningeal metastasis;

3. Any of the following medical histories:

• Systemic treatment with Chinese patent medicines with anti-lung cancerindications or immunomodulatory drugs (including thymosin, interferon,interleukin, excluding local use for the control of pleural effusion) within 2weeks before the first dose;

• Currently participating in interventional clinical research treatment, orreceiving other research drugs or using research devices within 4 weeks beforethe first dose; any drug still in the development stage needs to be washed outfor 5 half-lives (or discussed with the research team);

• Other major surgeries other than diagnosis or biopsy (excluding vascularaccess) within 4 weeks before the first dose, or major surgery is expectedduring the study;

• Palliative radiotherapy within 2 weeks before the first dose;

• Serious arterial/venous thrombotic events, including cerebrovascular accident (e.g., history of stroke or intracranial hemorrhage), deep vein thrombosis, andpulmonary embolism, occurred within 6 months before the first dose;

• Currently receiving (or unable to stop taking at least 1 week before the firstdose) drugs, herbal supplements, and foods that are known to be strong inducersor inhibitors of CYP3A;

• Prior to the first dose, there was a CTCAE caused by previous treatment > Grade 1 adverse events (except alopecia of any degree);

4. Receiving solid organ or blood system transplantation (such as previous allogeneicbone marrow transplantation or whole blood transfusion within 120 days of samplecollection during the study);

5. Previous interstitial lung disease, drug-induced interstitial lung disease,radiation pneumonitis requiring steroid hormone treatment, or current clinicallyactive interstitial lung disease (including interstitial lung changes), immunepneumonitis caused by immunotherapy;

6. Active autoimmune disease requiring systemic treatment (such as the use ofdisease-modifying drugs, corticosteroids or immunosuppressants) within 2 yearsbefore the first dose. Replacement therapy (such as thyroxine, insulin, orphysiological corticosteroids for adrenal or pituitary insufficiency) is notconsidered systemic treatment;

7. Diagnosed with immunodeficiency or receiving systemic glucocorticoid therapy or anyother form of immunosuppressive therapy within 7 days before the first dose of thestudy. Physiological doses of glucocorticoids (≤10 mg/day of prednisone orequivalent) are allowed;

8. Diagnosed with other malignancies within 5 years before the first dose, excludingbasal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/orcarcinoma in situ that has been evaluated to be clinically cured;

9. Vaccinated with live vaccines within 30 days before the first dose (cycle 1, day 1),including live attenuated vaccines, excluding inactivated vaccines;

10. Known active tuberculosis, such as positive tuberculin (PPD) test (nodule diameter > 10 mm), positive T-SPOT test, chest X-ray/CT Tuberculosis lesions are found, orother positive results are found based on routine clinical screening (except forthose who have been cured after standardized anti-tuberculosis treatment as assessedby the researchers);

11. Subjects currently have severe infectious diseases that are difficult to control andmust be excluded. After the recent infectious diseases are under control, theresearch team must determine whether they can be included in the group;

12. Subjects with active infections, including but not limited to hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and COVID-19active infections (determined by the researchers to be clinically significant, withsigns or symptoms, etc.). Testing for COVID-19 will be based on local practice;

13. Meet any of the following cardiac criteria:

• Congestive heart failure (CHF) classified as class II by the New York HeartAssociation (NYHA);

• Clinically significant valvular heart disease, hypertrophic or constrictivecardiomyopathy;

• Any clinically significant abnormalities on resting ECG, such as complete leftbundle branch block, 2/3 degree atrioventricular block, PR interval > 250 msec;

• Average calibrated QTcF > 470 msec of 3 resting ECGs during the screeningperiod;

• Subjects with any factors that may cause QT prolongation or increased risk ofarrhythmic events (e.g., heart failure, hypokalemia, congenital long QTsyndrome or a first-degree relative with long QT syndrome or a family historyof unexplained sudden death under the age of 40, or any concomitant medicationknown to cause QT prolongation);

• Ventricular arrhythmias requiring treatment;

• Acute myocardial infarction (AMI), unstable angina or new angina within 6months before the administration of this study;

14. Allergy to the drugs used in the study or their ingredients;

15. Intractable nausea and vomiting, chronic gastrointestinal diseases, difficultyswallowing drugs, intestinal obstruction or previous intestinal resection, which maylead to inability to fully absorb the study drugs;

16. Pregnant or lactating women;

17. Known bleeding diathesis, that is, hemophilia, von Willebrand disease;

18. The investigators assess that there are severe or uncontrollable systemic diseases (including poorly controlled hypertension and bleeding diseases) that cannot becarried out in clinical studies or may lead to poor compliance with clinicalstudies.