Clinical trial NCT06868836: A Study of JS207 (PD-1/VEGF Bispecific Antibody) in Combination With Chemotherapy in Advanced Non-small Cell Lung Cancer
Official title: A Phase II Study of JS207 (PD-1/VEGF Bispecific Antibody) in Combination With Pemetrexed and Platinum in Advanced Non-small Cell Lung Cancer With Actionable Genomic Alterations and TKI Therapy Failure
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Non-squamous Non-small Cell Lung Cancer
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
First posted: 2025-03-11
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: JS207 (10 mg/kg or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) + platinum-based chemotherapy (carboplatin: AUC5, d1 or cisplatin 75 mg/m², d1) every 3 weeks (Q3W) for a total of 4 cycles.
Primary purpose: TREATMENT

Brief summary: This study targets patients with advanced NSCLC driven with positive driver genes who have failed TKI treatment, enrolling 36-42 participants. Patients will receive JS207 (10 or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) + platinum-based chemotherapy (carboplatin AUC5 or cisplatin 75 mg/m², d1) every 3 weeks for 4 cycles. Afterward, JS207 and pemetrexed will continue as maintenance therapy until discontinuation criteria are met. The study aims to assess the safety, tolerability, and preliminary efficacy of JS207 combination therapy.

Detailed description: This study enrolls patients with advanced non-small cell lung cancer (NSCLC) who have positive driver genes and have failed TKI treatment. Approximately 36-42 patients are expected to be enrolled and receive treatment with JS207 (10 mg/kg or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) + platinum-based chemotherapy (carboplatin: AUC5, d1 or cisplatin 75 mg/m², d1) every 3 weeks (Q3W) for a total of 4 cycles.After the 4 cycles, patients will continue receiving JS207 (10 mg/kg or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) every 3 weeks (Q3W) until they meet the criteria for treatment discontinuation.The study aims to evaluate the safety, tolerability, and preliminary efficacy of JS207 in combination with pemetrexed and platinum-based chemotherapy.

Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 75 years old (both 18 and 75 years old included) at the time of signing the informed consent form, applicable to both males and females.
2. Locally advanced (stage IIIB/IIIC), metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) confirmed by histology or cytology, which is not eligible for radical surgery or radical chemoradiotherapy.
3. Positive for driver gene and having received the first-line targeted therapy approved by the National Medical Products Administration (NMPA).
4. Failure of previous tyrosine kinase inhibitor (TKI) treatment and currently having no standard TKI treatment available.
5. Positive for PD-L1 (tumor proportion score, TPS ≥ 1%) confirmed by the central laboratory test.
6. Being able to provide a qualified test report for positive driver gene, or agreeing to provide a qualified sample for driver gene testing.
7. According to the RECIST v1.1 criteria, the subject has at least 1 measurable lesion.
8. Performance status score of 0-1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
9. Expected survival period ≥ 12 weeks.
10. The function of important organs meets the requirements of the protocol.
11. Female subjects of childbearing potential, and male subjects whose partners are females of childbearing age, need to adopt a highly effective contraceptive measure during the study treatment period and for at least 6 months after the last administration.
12. Voluntarily joining this study, signing the informed consent form, having good compliance, and cooperating with the follow-up.

Exclusion Criteria:

1. Diseases accompanied by those listed in the protocol, including those with histopathological or cytopathological confirmation of the tumor combined with neuroendocrine tumor (including small cell lung cancer, large cell neuroendocrine carcinoma, etc.) components, or with the squamous cell carcinoma component exceeding 10%; known meningeal metastasis; symptomatic brain metastasis; the tumor encircling important blood vessels or with obvious necrosis and cavities, and the investigator deems that it may pose a risk of bleeding, etc.
2. Treatment received as listed in the protocol, including immunologically mediated treatment; drugs targeting the anti-VEGF pathway, etc.
3. Having an obvious bleeding tendency or a history of severe coagulation dysfunction.
4. Gastrointestinal perforation, intra-abdominal fistula or intra-abdominal abscess occurred within 6 months before the first administration, or currently having high-risk factors for perforation/fistula formation of the hollow viscus as judged by the investigator.
5. Having a serious, unhealed or ruptured wound, active ulcer or untreated fracture.
6. Having uncontrolled hypertension, or a history of hypertensive crisis or hypertensive encephalopathy.
7. Expected that the toxicity of previous anti-tumor treatment has not recovered to ≤ grade 1 according to the Common Terminology Criteria for Adverse Events (CTCAE).
8. Known allergy to the investigational drug or its excipients, pemetrexed, platinum drugs (carboplatin/cisplatin), or known history of ≥ grade 3 allergy to antibody drugs in the past.
9. Having an active autoimmune disease or a history of autoimmune disease.
10. Having a history of immunodeficiency.
11. Having a severe infection within 4 weeks before the first use of the investigational drug.
12. History of confirmed or suspected interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced pneumonia, idiopathic pneumonia, or other moderate to severe lung diseases that seriously affect lung function.
13. Active pulmonary tuberculosis infection detected by medical history or CT examination.
14. Having active tuberculosis, hepatitis B, or hepatitis C.
15. Having been diagnosed with any other malignant tumor within 5 years before the first use of the investigational drug.
16. Uncontrolled concurrent diseases listed in the protocol.
17. As judged by the investigator, having other severe, acute or chronic medical diseases, mental diseases or laboratory abnormalities that may increase the risk associated with participating in the study, or may interfere with the interpretation of the study results.

Primary outcomes:
measure: Investigator-assessed objective response rate (ORR)
timeFrame: Up to approximately 25 months
Secondary outcomes:
measure: Investigator-assessed objective response rate (DCR)
timeFrame: Up to approximately 25 months
measure: Investigator-assessed Duration of Response (DoR)
timeFrame: Up to approximately 25 months
measure: Investigator-assessed Progression-Free Survival (PFS)
timeFrame: Up to approximately 25months
measure: Investigator-assessed overall survival (OS)
timeFrame: Up to approximately 25 months
measure: Adverse Event
timeFrame: Up to approximately 25 months
measure: Number of participants with Laboratory examination indices
timeFrame: Up to approximately 25 months
Other outcomes:
measure: the trough concentrations (PK)
timeFrame: Up to approximately 25 months
measure: Immunogenicity(ADA)
timeFrame: Up to approximately 25 months
measure: Immunogenicity(NAb)
timeFrame: Up to approximately 25 months
measure: Expression level of PD-L1 in tumor tissues
timeFrame: Up to approximately 5 months
Locations:
city: Guangzhou
country: China
facility: Guangdong Provicial People's Hospital
state: Guangdong
Study officials:
affiliation: Medical Director
name: Weihua Wang, Doctor
role: STUDY_DIRECTOR
References: