SKB264 Plus KL-A167 in MSI-H/dMMR Advanced Gynecological Malignancies

Inclusion criteria

• 1. Age ≥18 years.
• 2. Histologically or cytologically confirmed recurrent or metastatic ovarian cancer, endometrial cancer, or cervical cancer.
• 3. dMMR or MSI-H subtype (defined as: deficiency/loss of mismatch repair (MMR) proteins MLH1, PMS2, MSH2, or MSH6 expression detected by immunohistochemistry (IHC), or identified as MSI-H by polymerase chain reaction (PCR)/next-generation sequencing (NGS)).
• 4. Received at least 1 prior systemic regimen (prior anti-PD-1/L1 allowed) for recurrent or metastatic ovarian cancer, endometrial cancer, or cervical cancer.
• 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• 6. Life expectancy more than 12 weeks.
• 7. At least one measurable lesion per RECIST 1.1 criteria.
• 8. Subjects must have recovered from all toxicities related to prior therapies, except for toxicities not considered a safety risk.
• 9. Adequate function of the important organs.
• 10. For female subjects of childbearing potential effective medical contraception must be used from the time of signing the informed consent form until 6 months after the last dose of the drug.

• Participants must voluntarily participate in the study, sign an informed consent form, exhibit good compliance, and cooperate with follow-up assessments.

Exclusion criteria

• 1. Subjects with known other malignant tumors that are progressing or require active treatment within the past 3 years.
• 2. Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or other active CNS metastases. Subjects with locally treated brain metastases may participate provided they are clinically stable for at least 4 weeks, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment;
• 3. Subjects with clinically significant cardiovascular diseases.
• 4. Subjects with severe and/or uncontrolled concomitant diseases, such as uncontrolled hypertension, symptomatic or recurrent pleural effusion, pericardial effusion, or ascites requiring drainage.
• 5. Subjects diagnosed with active hepatitis B or active hepatitis C.
• 6. Subjects with known uncontrolled HIV infection.
• 7. Subjects with known active tuberculosis.
• 8. Subjects with documented severe dry eye syndrome, severe meibomian gland dysfunction and/or blepharitis, or a history of corneal disorders that impair or delay corneal healing.
• 9. Subjects who have undergone major surgery (as defined by the investigator) within 30 days prior to the first dose of study treatment or who have not recovered from prior surgery.
• 10. Subjects with known hypersensitivity or anaphylaxis to the study drug or its excipients; or a history of severe hypersensitivity reactions to monoclonal antibodies.
• 11. Subjects with a history of interstitial lung disease (ILD) or non-infectious pneumonia requiring steroid treatment, currently suffering from ILD/pneumonia, or unable to rule out suspected ILD/pneumonia through imaging at screening.
• 12. Subjects with a history of allogeneic tissue/organ transplantation.
• 13. Subjects with autoimmune diseases requiring systemic treatment within the past 2 years or requiring immunosuppressive treatment during the study period. Subjects with controllable type 1 diabetes, thyroiditis with normal thyroid function, or hypothyroidism well controlled by hormone replacement therapy (HRT), or skin diseases (such as vitiligo, psoriasis) that do not require systemic treatment can be included.
• 14. Subjects who have previously received TROP2-targeted drugs or any therapy containing a topoisomerase I inhibitor, including antibody-drug conjugates (ADCs).
• 15. Subjects who have previously used any experimental anti-tumor vaccines.
• 16. Subjects who received live vaccines within 30 days prior to the first dose of study treatment or plan to receive live vaccines during the study.
• 17. Subjects who need to use strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) within 2 weeks before the first study treatment and during the study period.
• 18. Subjects who received any chemotherapy, radiotherapy, immunotherapy, or biologic therapy within 4 weeks prior to the first dose of study treatment; subjects who received small molecule tyrosine kinase inhibitors (TKIs), anti-tumor hormone therapy, systemic immunostimulants (including but not limited to interferon, IL-2), or approved anti-tumor Chinese herbal preparations within 2 weeks before the first study treatment.
• 19. Subjects who received systemic anti-infective treatment within 2 weeks prior to the first dose of study treatment.
• 20. Pregnant or lactating women.
• 21. Any other conditions deemed by the investigator to make the patient unsuitable for participation in this study.