Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626000937314p
Ethics application status
Help: Ethics application status
Not yet submitted
Date submitted
Help: Date submitted
30/06/2026
Date registered
Help: Date registered
29/07/2026
Date last updated
Help: Date last updated
29/07/2026
Date data sharing statement initially provided
Help: Data sharing statement date
29/07/2026
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the activity and safety of pembrolizumab in combination with sacituzumab tirumotecan in mismatch repair proficient advanced or recurrent endometrial cancer
Scientific title
IMPACT - A phase 2 study of IMmunotherapy with Pembrolizumab and sACituzumab Tirumotecan in pMMR recurrent or advanced endometrial cancer
Additional trial identifiers [1] 317613 0
CTC 0413
Universal Trial Number (UTN)
Trial acronym
IMPACT
Related trial records

Health condition
Health condition(s) studied:
Endometrial cancer 342393 0
Condition category
Condition code
Cancer 338517 338517 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
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
Intervention code [1] 334436 0
Treatment: Drugs
Description of the comparator or control
This study is a single-arm non-randomised study. No data will be collected for comparator/ control.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 345802 0
Objective response rate (ORR) according to RECIST version 1.1 in participants with recurrent or advanced pMMR endometrial cancer.
Timepoint [1] 345802 0
Tumour assessments will be performed at screening, 6 weeks and 12 weeks after registration, then every 12 weeks thereafter until disease progression, commencement of new anticancer therapy, withdrawal of consent, death, or study closure. Participants may remain in survival follow-up until death or study closure, which is anticipated to be at least 12 months after enrolment of the last participant.
Secondary outcome [1] 463368 0
Duration of response
Timepoint [1] 463368 0
Assessed from first documented response until disease progression, withdrawal of consent, death, or study closure. Tumour assessments occur at screening, 6 weeks, 12 weeks and every 12 weeks thereafter.
Secondary outcome [2] 463369 0
Progression Free Survival
Timepoint [2] 463369 0
Participants will undergo tumour assessments at screening, 6 weeks, 12 weeks and every 12 weeks thereafter until disease progression. Survival follow-up will occur every 12 weeks following treatment discontinuation until death or study closure.
Secondary outcome [3] 463370 0
Overall Survival
Timepoint [3] 463370 0
Participants will be followed up from date of registration until the end of study which is estimated to be at least 12 months after accrual of the last participant.
Secondary outcome [4] 463371 0
Safety
Timepoint [4] 463371 0
Safety events will be recorded from investigational product assignment until 30 days following last dose of investigational product.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Healthy volunteers
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Historical control data was used to calculate sample size. This was derived from the chemotherapy-alone arm of the NRG-GY018 phase III study (Eskander et al, NEJM 2023) in patients with advanced or recurrent pMMR endometrial cancer. The null hypothesis ORR of 50% used for the study sample size calculation is based on outcomes reported from NRG-GY018.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2027
Actual
Date of last participant enrolment
Anticipated
31/08/2028
Actual
Date of last data collection
Anticipated
31/08/2029
Actual
Sample size
Target
23
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 322166 0
Commercial sector/Industry
Name [1] 322166 0
Merck Sharp & Dohme (MSD)
Country [1] 322166 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Country
Australia
Secondary sponsor category [1] 325065 0
None
Name [1] 325065 0
Address [1] 325065 0
Country [1] 325065 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 320699 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 320699 0
Ethics committee country [1] 320699 0
Australia
Date submitted for ethics approval [1] 320699 0
24/08/2026
Approval date [1] 320699 0
Ethics approval number [1] 320699 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 151322 0
Dr Peey-Sei Kok
Address 151322 0
NHMRC Clinical Trials Centre, The University of Sydney, Missenden Road, Camperdown NSW 2050
Country 151322 0
Australia
Phone 151322 0
+61 2 9562 5000
Fax 151322 0
Email 151322 0
[email protected]
Contact person for public queries
Name 151323 0
IMPACT Trial Coordinating Centre
Address 151323 0
NHMRC Clinical Trials Centre, The University of Sydney, Missenden Road, Camperdown NSW 2050
Country 151323 0
Australia
Phone 151323 0
+61 2 9562 5000
Fax 151323 0
Email 151323 0
[email protected]
Contact person for scientific queries
Name 151324 0
Dr Peey-Sei Kok
Address 151324 0
NHMRC Clinical Trials Centre, The University of Sydney, Missenden Road, Camperdown NSW 2050
Country 151324 0
Australia
Phone 151324 0
+61 2 9562 5000
Fax 151324 0
Email 151324 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Any type of analysis (i.e. no restrictions on data re-use)
When can requests for individual participant data be made (start and end dates)?
From:
At the end of the study and after publication of main results

To:
No end date
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: [email protected]

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.