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

NCT07738757 | Not Yet Recruiting Phase 2

• 1 other identifier: K10649
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

This is a prospective, open-label, multicenter, single-arm Phase II study designed to evaluate the efficacy and safety of sacituzumab tirumotecan (sac-TMT/SKB264) in combination with tagitanlimab (KL-A167) as second-line or later therapy in patients with recurrent or metastatic MSI-H/dMMR gynecological malignancies, including endometrial cancer, ovarian cancer, and cervical cancer. The primary objective is to evaluate the objective response rate (ORR) per RECIST v1.1 as assessed by the investigator. Secondary objectives include evaluating overall survival (OS), progression-free survival (PFS) per RECIST v1.1, disease control rate (DCR), duration of response (DoR), and the safety and tolerability of the combination regimen.

Conditions

Recurrent or Metastatic MSI-H/dMMR Gynecological Malignancies

Outcome Measures

Primary Outcomes (1)

• Objective response rate(ORR)

  Ãbjective Response Rate (ÃRR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR). assessed byInvestigator based on RECiST version 1.1.

  up to 24 months

Secondary Outcomes (5)

• Progression-free survival(PFS)

  up to 24 months

• Duration of response (DoR)

  up to 24 months

• Disease control rate(DCR)

  up to 24 months

• Overall survival(OS)

  up to 5 years

• Incidence and severity of adverse events (AEs)

  up to 24 months

Study Arms (2)

Cohort 1: Endometrial cancer

EXPERIMENTAL

Drug: Sacituzumab Tirumotecan (Sac-TMT); Drug: Tagitanlimab

Cohort 2: Ovarian cancer & Cervical cancer

EXPERIMENTAL

Drug: Sacituzumab Tirumotecan (Sac-TMT); Drug: Tagitanlimab

Interventions

Sacituzumab Tirumotecan (Sac-TMT) DRUG

Sac-TMT will be administered as an intravenous (IV) infusion every 2 weeks on Day 1 of each 14-day cycle.

Also known as: SKB264

Cohort 1: Endometrial cancer; Cohort 2: Ovarian cancer & Cervical cancer

Tagitanlimab DRUG

KL-A167 will be administered as an intravenous (IV) infusion every 2 weeks on Day 1 of each 14-day cycle. KL-A167 therapy for up to 2 years.

Also known as: KL-A167

Cohort 1: Endometrial cancer; Cohort 2: Ovarian cancer & Cervical cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥18 years.
• \. Histologically or cytologically confirmed recurrent or metastatic ovarian cancer, endometrial cancer, or cervical cancer.
• \. 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)).
• \. Received at least 1 prior systemic regimen (prior anti-PD-1/L1 allowed) for recurrent or metastatic ovarian cancer, endometrial cancer, or cervical cancer.
• \. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• \. Life expectancy more than 12 weeks.
• \. At least one measurable lesion per RECIST 1.1 criteria.
• \. Subjects must have recovered from all toxicities related to prior therapies, except for toxicities not considered a safety risk.
• \. Adequate function of the important organs.
• \. 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.

You may not qualify if:

• \. Subjects with known other malignant tumors that are progressing or require active treatment within the past 3 years.
• \. 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;
• \. Subjects with clinically significant cardiovascular diseases.
• \. Subjects with severe and/or uncontrolled concomitant diseases, such as uncontrolled hypertension, symptomatic or recurrent pleural effusion, pericardial effusion, or ascites requiring drainage.
• \. Subjects diagnosed with active hepatitis B or active hepatitis C.
• \. Subjects with known uncontrolled HIV infection.
• \. Subjects with known active tuberculosis.
• \. 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.
• \. 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.
• \. Subjects with known hypersensitivity or anaphylaxis to the study drug or its excipients; or a history of severe hypersensitivity reactions to monoclonal antibodies.
• \. 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.
• \. Subjects with a history of allogeneic tissue/organ transplantation.
• \. 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.
• \. Subjects who have previously received TROP2-targeted drugs or any therapy containing a topoisomerase I inhibitor, including antibody-drug conjugates (ADCs).
• \. Subjects who have previously used any experimental anti-tumor vaccines.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (2)

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

Location

Peking Union Medical College Hospital

Beijing, 100730, China

Location

MeSH Terms

Conditions

Recurrence

Interventions

18-O-demethylcervinomycin A2

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Yang Xiang

CONTACT

010-69156068; xiangy@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: July 31, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 30, 2029
• Last Updated: July 31, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)