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

Official title

A Phase II Study of Sacituzumab Tirumotecan (Sac-TMT/SKB264) in Combination With Tagitanlimab (KL-A167) as Second-Line or Later Therapy for MSI-H/dMMR Advanced Gynecological Malignancies: An Open-Label, Single-Arm, Multicenter Exploratory Trial

Overview

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.

Interventions

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

Primary outcome measures

• Objective response rate(ORR) [Time frame: up to 24 months]

Secondary outcome measures (5)

• Progression-free survival(PFS) [Time frame: up to 24 months]
• Duration of response (DoR) [Time frame: up to 24 months]
• Disease control rate(DCR) [Time frame: up to 24 months]
• Overall survival(OS) [Time frame: up to 5 years]
• Incidence and severity of adverse events (AEs) [Time frame: up to 24 months]

Eligibility criteria

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.

11\. 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Qilu Hospital of Shandong University — Jinan
• Peking Union Medical College Hospital — Beijing

Identifiers

NCT: NCT07738757 · K10649

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗