JS207 (PD‑1/VEGF bispecific) plus chemotherapy for advanced non-squamous NSCLC after TKI failure

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

This trial will test whether combining JS207 with pemetrexed and platinum chemotherapy can help people with advanced non-squamous NSCLC who have driver gene changes and have stopped responding to TKIs.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Junshi Bioscience Co., Ltd. (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06868836 on ClinicalTrials.gov

What this trial studies

This open-label Phase 2 study will enroll about 36–42 patients with advanced non-squamous NSCLC who are driver-gene positive and have progressed after approved first-line TKI therapy. Participants receive JS207 (10 or 15 mg/kg IV on day 1) plus pemetrexed (500 mg/m² IV on day 1) and either carboplatin (AUC5) or cisplatin (75 mg/m²) every 3 weeks for four cycles. After four cycles, patients continue maintenance treatment with JS207 and pemetrexed every 3 weeks until discontinuation criteria are met. The trial is designed to collect safety, tolerability, and preliminary efficacy data, with central or local testing required for PD‑L1 and driver gene status.

Who should consider this trial

Good fit: Adults aged 18–75 with locally advanced, metastatic, or recurrent non-squamous NSCLC that is driver-gene positive, PD‑L1 TPS ≥1%, measurable by RECIST v1.1, and who have progressed after approved first-line TKI therapy are the intended participants.

Not a fit: Patients with squamous histology, PD‑L1 <1%, no qualifying driver gene, or those who cannot tolerate platinum-based chemotherapy or have significant organ dysfunction are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this combination could offer a new treatment option that controls disease longer or improves outcomes for patients who no longer benefit from approved TKIs.

How similar studies have performed: The bispecific PD‑1/VEGF approach is novel, but prior trials combining PD‑1/PD-L1 inhibitors with VEGF blockade and chemotherapy have shown positive signals in NSCLC, including in some patients previously treated with targeted therapies.

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 or local 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.

Where this trial is running

Guangzhou, Guangdong

• Guangdong Provicial People's Hospital — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Ying Zhang, Master

Conditions: Non-squamous Non-small Cell Lung Cancer