JS212 and JS213 alone and in combination for advanced solid tumors

A Phase II Clinical Study Evaluating the Safety, Tolerability,Pharmacokinetics, and Preliminary Efficacy of JS212 andJS213 as Monotherapy and in Combination in Patients Withadvanced Malignant Solid Tumors

This trial will test whether JS212 and JS213, given alone or combined with each other or with JS207 or toripalimab, can shrink tumors in people with advanced solid tumors who have progressed after standard treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 480 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Junshi Bioscience Co., Ltd. (Academic / other)
• Drugs / interventions: bevacizumab, chemotherapy, immunotherapy, toripalimab
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07480733 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label Phase II trial enrolls patients into five cohorts to study JS212 and JS213 as single agents and in combination regimens. The primary endpoint is investigator‑assessed objective response rate, with secondary endpoints including safety, tolerability, and pharmacokinetics. Eligible patients have measurable metastatic or unresectable clear cell renal cell carcinoma, castration‑resistant prostate cancer, urothelial carcinoma, or unresectable Stage III/IV melanoma and must have progressed on the specified prior therapies. Treatment cohorts are JS212 alone, JS213 alone, JS212+JS213, JS212+JS207, and JS212+toripalimab, with responses measured by RECIST v1.1.

Who should consider this trial

Good fit: Adults 18–75 with measurable metastatic or unresectable clear cell RCC, castration‑resistant prostate cancer, urothelial carcinoma, or Stage III/IV melanoma who have progressed on the specified prior therapies and meet performance and lab criteria are ideal candidates.

Not a fit: Patients with tumor types not listed, those who have not received the required prior treatments, those with poor performance status or major organ dysfunction, or those unable to travel to study visits are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, these regimens could provide new options that shrink tumors or extend disease control for patients whose cancers no longer respond to approved therapies.

How similar studies have performed: Combining novel targeted agents with PD‑1 inhibitors has shown promise in other cancers, but JS212 and JS213 are experimental and have limited published efficacy data so far.

Eligibility criteria

Inclusion Criteria:

1. Age 18 to 75 years, male or female.
2. Histologically confirmed metastatic or unresectable clear cell renal cell carcinoma (RCC); histologically or cytologically confirmed metastatic or unresectable castration-resistant prostate cancer (CRPC); histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma (UC); histologically confirmed unresectable Stage III or IV melanoma.
3. For RCC: disease progression following prior anti-angiogenic targeted therapy and PD-(L)1 inhibitor therapy; for CRPC: disease progression following prior abiraterone or novel androgen receptor (AR) inhibitor therapy; for UC: disease progression following prior PD-(L)1 inhibitor and platinum-based chemotherapy; for melanoma: disease progression following prior chemotherapy and PD-(L)1 inhibitor therapy.
4. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
6. Life expectancy ≥ 12 weeks.
7. Adequate organ function.
8. Male and female subjects of reproductive potential must agree to use highly effective contraception during the study and avoid conception; women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose and must not be breastfeeding.
9. CRPC subjects must be on continuous luteinizing hormone-releasing hormone agonist (LHRHa) therapy or have undergone bilateral orchiectomy; subjects without bilateral orchiectomy must plan to maintain effective LHRHa therapy throughout the study; castrate levels of testosterone at screening; metastatic disease confirmed by CT/MRI or radionuclide bone scan.
10. Subjects voluntarily participate in the study and have signed the informed consent form.

Exclusion Criteria:

1. Major surgery, radiotherapy, chemotherapy, immunotherapy or other anti-tumor therapy, or other investigational agents administered prior to the first study dose.
2. Toxicity from prior anti-tumor therapy has not recovered to ≤ Grade 1 per CTCAE v5.0 or to the level specified in the inclusion/exclusion criteria.
3. Presence of active central nervous system (CNS) metastases.
4. Presence of clinically significant pleural effusion, ascites, or pericardial effusion requiring repeated intervention.
5. Uncontrolled hypertension despite medical therapy, or history of hypertensive crisis or hypertensive encephalopathy.
6. Severe cardiovascular or cerebrovascular disease.
7. History of interstitial lung disease (ILD)/non-infectious pneumonitis requiring corticosteroid therapy.
8. Severe bone injury due to tumor bone metastasis as judged by the investigator.
9. Severe infection (CTCAE v5.0 \> Grade 2) within 28 days prior to the first study dose.
10. Active tuberculosis, hepatitis B, or hepatitis C infection.
11. History of immunodeficiency, or known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
12. History of another primary malignancy, except those with curative treatment and no known active disease for \>5 years and low potential risk of recurrence.
13. Known hypersensitivity or severe allergic reaction to the study treatment, any of its components, or excipients.
14. Presence of any other condition that may result in premature discontinuation from the study.
15. Diagnosis of any other malignancy within 5 years.
16. Subjects participating in Cohorts 1, 3, 4, and 5:Prior treatment with an ADC targeting EGFR and/or HER3, or prior treatment with an ADC utilizing a topoisomerase I inhibitor as the payload.
17. Subjects participating in Cohorts 2, 3, 4, and 5:Administration of any live or live-attenuated vaccine within 28 days prior to the first dose, or anticipated need for such vaccination during the study.Use of systemic corticosteroids or other immunosuppressive agents for ≥7 consecutive days within 14 days prior to the first dose.Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose.Development of a drug-related adverse event leading to permanent discontinuation of prior anti-PD-(L)1 antibody therapy.
18. Subjects participating in Cohorts 4:Imaging in the screening period demonstrates tumor encasement of major blood vessels, significant necrosis, or cavitation that, in the investigator's opinion, may confer a bleeding risk.Clinically significant hemoptysis or tumor bleeding of any cause within 28 days prior to the first dose.Gastrointestinal perforation, fistula, or intra-abdominal abscess within 6 months prior to enrollment, or current high risk of hollow organ perforation/fistula formation as judged by the investigator.History of gastrointestinal bleeding within 6 months prior to enrollment, or documented gastrointestinal bleeding tendency.Severe, non-healing or dehiscent wound, active ulcer, or untreated fracture.Significant bleeding diathesis or severe coagulopathy.Use of antiplatelet therapy or therapeutic anticoagulation within 14 days prior to the first dose.Development of a drug-related adverse event leading to permanent discontinuation of prior bevacizumab or similar agent therapy.

Where this trial is running

Beijing, Beijing Municipality

• Peking University Cancer Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Yuteng Shen, Project manager

Conditions Advanced Malignant Solid Tumors