Neo-adjuvant pembroliuzmab as an alternative treatment for MMRd uterine cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Neoplasms [C04]

Trial duration

18 Dec 2023 → ongoing

Decision date (initial)

2024-09-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

MSD · KWF

External identifiers

EU CT number

2024-516736-10-00

EudraCT number

2022-003922-27

ClinicalTrials.gov

NCT06180733

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary objective of this phase 2 trial is to establish the fraction of patients that achieve a major pathologic response (MPR) after 9 cycles of pembrolizumab, with the ultimate aim of informing a follow-up randomized trial. MPR was chosen as primary endpoint to align with ongoing randomized phase 3 ICB trials on neo-adjuvant vs. adjuvant treatment in other tumor types (e.g. the NADINA trial in melanoma; NCT04949113).

Secondary objectives 3

1. To establish the objective response rate by radiologic assessment using MRI and RECIST1.1
2. To establish recurrence free survival (RFS) defined as the number of patients alive without any progress or recurrence at two years from disease diagnosis
3. To assess safety and tolerability of 9 cycles of neo-adjuvant pembrolizumab in the treatment of MMRd UC

Conditions and MedDRA coding

Mismatch repair deficient endometrial cancer / uterine cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed primary diagnosis of G3/CC MMRd uterine cancer who are intended to be treated with hysterectomy.
2. A female participant is eligible to participate if she is not pregnant, not breastfeeding, is not a woman of childbearing potential (WOCBP) or agrees to follow contraceptive guidance during the treatment period and at least until standard-of-care hysterectomy.
3. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

Exclusion criteria 19

1. A WOCBP who has a positive serum pregnancy test at screening.
2. Has 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 (eg, CTLA-4, OX-40, CD137).
3. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to allocation.
4. Has received prior radiotherapy within 2 weeks of start of study treatment or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease with a 1-week washout is permitted.
5. Has received a live vaccine or live-attenuated vaccine within 30 days before to the first dose of study intervention. Administration of killed vaccines and Covid vaccines is allowed.
6. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
9. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
11. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid).
12. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
13. Has an active infection requiring systemic therapy.
14. Has a known history of Human Immunodeficiency Virus (HIV).
15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
16. Has not adequately recovered from major surgery or has ongoing surgical complications.
17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
19. Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main study endpoint is the fraction of patients that achieve a MPR. that the study is considered positive if neo-adjuvant pembrolizumab induces MPRs in at least 74% of patients.

Secondary endpoints 3

1. The objective response rate of the tumor determined by radiologic assessment using MRI and RECIST1.1.
2. Recurrence-free survival 2 years from disease diagnosis.
3. The safety and tolerability of 9 cycles of neo-adjuvant pembrolizumab in the treatment of MMRd UC.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Prof. dr. H.W. Nijman

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Prof. dr. H.W. Nijman

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications