None listed
Conditions
Brief summary
Brief description of the study purpose The IMPACT study is a Phase 2 clinical trial investigating whether a combination of pembrolizumab (an immunotherapy) and sacituzumab tirumotecan (Sac-TMT, a targeted chemotherapy delivery treatment) can safely and effectively treat endometrial cancer that has returned or spread. The study aims to determine whether this combination can improve tumour control while remaining well tolerated. Who is it for? You may be eligible for this study if you are aged 18 years and older with recurrent or advanced endometrial cancer that cannot be treated with curative surgery or radiotherapy. Participants must have mismatch repair proficient (pMMR) disease, measurable cancer on imaging, good physical functioning, and adequate organ function. Study details All those who are eligible will receive the combination treatment. Pembrolizumab will be given as an intravenous (IV) infusion every 6 weeks for up to 2 years, and sacituzumab tirumotecan will be given as an IV infusion every 2 weeks for up to approximately 3 years, or until the cancer progresses or side effects become unacceptable. All enrolled participants will receive the same treatment combination. Participants will attend regular study visits and undergo assessments including physical examinations, blood tests, imaging scans to measure tumour response, and monitoring for side effects and overall health. It is hoped that this research will help determine whether combining pembrolizumab with sacituzumab tirumotecan is an effective treatment option for people with recurrent or advanced endometrial cancer and may contribute to improved treatment outcomes in the future.
Interventions
Pembrolizumab 400 mg intravenous infusion every 6 weeks (maximum 2 years) and sacituzumab tirumotecan 4 mg/kg intravenous infusion every 2 weeks (maximum 78 doses; approximately 3 years) until progression or intolerable toxicity
Sponsors
The University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults, aged 18 and older, with histologically confirmed diagnosis of endometrial cancer of all histologies (except for carcinosarcoma or sarcoma) and documented mismatch repair proficient (pMMR) status. 2. Advanced (stage III or IV) or recurrent disease that is not amenable to local therapy with curative intent such as surgical resection and/or radiotherapy. 3. In the recurrent setting, disease recurrence following one prior platinum-based chemotherapy regimen administered with curative intent is permitted. 4. In the metastatic setting, no prior systemic therapy is permitted for the treatment of metastatic disease. 5. At least one measurable target lesion per RECIST v1.1 is required. 6. Prior endocrine therapy and/or use of a levonorgestrel-releasing intrauterine system (e.g., Mirena) for the treatment of endometrial cancer is permitted. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 8. Adequate bone marrow, liver, and renal function (done within 10 days prior to study intervention) and with values within specified ranges. 9. Chronic hepatitis B carrier with undetectable hepatitis DNA level is allowed. 10. Participants with a history of hepatitis C (HCV) infection are eligible if HCV viral load is undetectable at screening. 10. Participants living with human immunodeficiency virus (HIV) must have well-controlled HIV on antiretroviral therapy.
Exclusion criteria
1. MMR deficient endometrial carcinoma. 2. Carcinosarcoma or sarcoma of endometrium, including mixed histological subtypes containing carcinosarcoma or sarcomatous components. 3. Candidate for curative-intent surgery or curative-intent radiotherapy at the time of enrollment. 4. Had received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor. 5. Received prior treatment with another TROP2-targeted antibody drug conjugate (ADC) or with a topoisomerase 1 inhibitor-containing ADC. 6. Had received prior systemic anticancer therapy within 3 weeks before the first dose of study intervention. 7. Had received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids. 8. Suspected brain or leptomeningeal metastases, untreated brain metastases or current clinical or radiological progression of known brain metastases, or requirement for steroid therapy for brain metastases. 9. Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing. 10. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. 11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 12. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention. 13. History of another concurrent active malignancy that requires ongoing treatment. 14. History of stem cell/solid organ transplant. 15. Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of treatment with study intervention. 16. Severe hypersensitivity (Grades =3) to study intervention, any of its/their excipients, and/or to another biologic therapy. 17. Has had major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention. 18. Has a history of (non-infectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/interstitial lung disease, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening. 19. Has an active autoimmune disease that has required systemic treatment in past 2 years. 20. Has a diagnosis of primary immunodeficiency or is receiving systemic steroid therapy. 21. Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial. 22. Has a known history of active TB (Bacillus Tuberculosis). 23. Has an active infection requiring systemic therapy.
Outcome results
None listed