A Phase II Clinical Study Evaluating the Combination Therapy of JS212 in Patients With Advanced Lung Cancer

Part One:

The plan involves including patients with previously failed standard treatments in advanced NSCLC and ES-SCLC. It consists of two phases: safety introduction and clinical expansion, covering cohorts 1 to 3.

The safety introduction phase will explore the safety of the following combined regimens in the target population:

Queue 1: JS212 + JS207 Queue 2: JS212 + Toripalimab Queue 3: JS212 + JS213

Part Two:

It is planned to include lung cancer patients who have not received any systemic anti-tumor treatment for advanced NSCLC and ES-SCLC in the past. If the SMC decides to further combine chemotherapy, the safety introduction phase should also include to ensure the safety of the subjects.

Inclusion criteria

• The age between 18 and 75 years old, and any gender.
• Local advanced, metastatic or recurrent NSCLC.
• ES-SCLC.
• According to the Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), there must be at least one measurable lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Expected survival period of ≥ 12 weeks.
• The functions of important organs meet the requirements.
• Female participants with reproductive capacity (WOCBP) who have sexual life with an unsterilized male partner and who have signed the informed consent must have a negative serum pregnancy test result within 7 days before the first administration, and must agree to take effective contraceptive measures from the time of signing the ICF until 7 months after the last administration of the study.
• Unsterilized male participants who have sexual life with a fertile female partner must agree to use the effective contraceptive measures after signing the ICF until 4 months after the last administration of the study. During this period, sperm donation is prohibited.
• The participants voluntarily participate in this study and sign the informed consent.

Exclusion criteria

• Accompanying the following disease states:

• Tumor histological or cytological pathological confirmation of combined large cell neuroendocrine carcinoma or sarcomatoid lesion, or NSCLC with small cell lung cancer component;
• NSCLC patients with positive driver mutations;
• Patients with known meningeal metastasis;
• Patients with symptomatic brain metastases;
• Uncontrolled pleural effusion, pericardial effusion, or recurrent ascites;
• Unatable spinal cord compression;

• Participants in Cohort 1 and Cohort 4 need to exclude any of the following conditions:

• Within one month before the first use of the study drug, any clinically significant hemoptysis or tumor bleeding;
• High bleeding risk; tumor invading important organs, high risks of perforation, esophageal-tracheal fistula, massive hemoptysis, etc.;
• Obvious bleeding tendency or severe coagulation dysfunction history, etc;
• Recent gastrointestinal perforation, gastrointestinal obstruction, trachea-esophageal fistula, abdominal fistula or intra-abdominal abscess, or currently having high-risk factors for hollow organ perforation/ fistula formation, or active inflammatory bowel disease, etc;
• Presence of severe, non-healed or open wounds, active ulcers or untreated fractures;
• Have poorly controlled hypertension;
• Have used antiplatelet drugs or anticoagulant therapy within 14 days;
• Have experienced a drug-related adverse event that led to permanent discontinuation of the medication during previous Bevacizumab and similar agent treatments;

• Have received any of the following treatments:

• Immune-mediated treatments (only for part Two);
• Have received any investigational drug within 4 weeks or 5 half-lives before the first use of the study drug;
• Have been enrolled in another clinical study;
• Have undergone major surgery within 4 weeks;
• Have received local small-scale radiotherapy within 14 days;

4.Have not recovered to ≤ CTCAE grade 1 toxicity or the level specified in the inclusion/exclusion criteria.

5.Have known allergies to any study treatment or its excipients or have experienced an allergic reaction.

6.Have experienced a drug-related AE that led to permanent discontinuation of the anti-PD-(L)1 antibody treatment.

7.Have any of the following cardiac examination results:

• Long QT;
• Left ventricular ejection fraction (LVEF) < 50%;

8.Have a history of diagnosed or suspected ILD, drug-induced pneumonia, or other severe lung diseases.

9.Have experienced a severe infection within 4 weeks.

10.Have a history of immunodeficiency, or have a history of organ transplantation and allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation.

11.Have active pulmonary tuberculosis infection.

12.Have active hepatitis.

• Uncontrolled concurrent diseases.

• Participants who were diagnosed with any other malignant tumor within 5 years.

• Female participants who are pregnant, breastfeeding, or planning to become pregnant during the study period.

• Other conditions for trial participation were not considered appropriate by the investigator.