New drug combo targets tough cancers in Mid-Stage trial

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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.