Phase II Study of JS212/JS213 as Monotherapy and in Combination in Patients With Advanced Malignant 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 is a multicenter, open-label Phase II clinical study. The primary objective is to evaluate the investigator-assessed objective response rate of JS212 and JS213 as monotherapy and in combination regimens in patients with advanced solid tumors. This study aims to explore the safety, tolerability, and preliminary efficacy of JS212, JS213, as well as JS212 in combination with JS213, toripalimab, and JS207.

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignant Solid Tumors
• Intervention / Treatment: Drug: JS212 for Injection; Drug: JS213 for Injection; Drug: JS207 for Injection; Drug: Toripalimab

Detailed Description

This study is a Phase II clinical trial designed to evaluate the safety, tolerability, PK characteristics, and preliminary efficacy of JS212 and JS213 as monotherapy and in combination therapy in patients with advanced malignant solid tumors. This study plans to conduct 5 treatment cohorts:

Cohort 1: JS212 Cohort 2: JS213 Cohort 3: JS212 + JS213 Cohort 4: JS212 + JS207 Cohort 5: JS212 + Toripalimab

• Study Type: Interventional
• Enrollment (Estimated): 410
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yuteng Shen, Project manager; Phone Number: 8618612107811; Email: yuteng_shen@junshipharma.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Peking University Cancer Hospital
      • Principal Investigator: Jun Guo, Ph.D
      • Contact: Jun Guo, Ph.D; Phone Number: 086 010-88196317; Email: guoj307@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 or PD-(L)1 inhibitor and ADC drugs; for melanoma: disease progression following prior chemotherapy and/or 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 v6.0 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 v6.0 > 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: JS212 Monotherapy	Drug: JS212 for Injection; administered by intravenous infusion on Day 1 of each 21-day cycle.
Experimental: Arm 2: JS213 Monotherapy	Drug: JS213 for Injection; administered by intravenous infusion on Day 1 of each 21-day cycle.
Experimental: Arm 3: JS212 in Combination with JS213	Drug: JS212 for Injection; administered by intravenous infusion on Day 1 of each 21-day cycle.; Drug: JS213 for Injection; administered by intravenous infusion on Day 1 of each 21-day cycle.
Experimental: Arm 4: JS212 in Combination with JS207	Drug: JS212 for Injection; administered by intravenous infusion on Day 1 of each 21-day cycle.; Drug: JS207 for Injection; administered by intravenous infusion on Day 1 of each 21-day cycle.
Experimental: Arm 5: JS212 in Combination with Toripalimab	Drug: JS212 for Injection; administered by intravenous infusion on Day 1 of each 21-day cycle.; Drug: Toripalimab; administered by intravenous infusion on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective response rate(ORR), assessed by investigator ( per RECIST v1.1).	up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	overall survival (OS)	up to 6 years
Safety (AE)	Incidence and severity of adverse events (AEs)	up to 6 years
Number of Participants With Abnormal Laboratory Values or clinical findings	Abnormal laboratory or clinical findings	up to 6 years
dose-limiting toxicity（DLT）	Incidence and severity of dose-limiting toxicity（DLT）	up to 6 years
PFS	Progression-free survival (PFS), assessed by investigators (per RECIST v1.1)	up to 6 years
DoR	Duration of response (DoR), assessed by investigators	up to 6 years
DCR	Disease control rate (DCR), assessed by investigators	up to 6 years

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 11, 2028

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Drug Administration Routes; Drug Therapy; Injections; toripalimab
• Other Study ID Numbers: JS212-004-II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No