Phase 3 study of pembrolizumab vs chemotherapy in dMMR advanced or recurrent endometrial carcinoma

JRCT ID: jRCT2011210065

Registered date:30/01/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Endometrial cancer
• Date of first enrollment: 20/04/2022
• Target sample size: 20
• Countries of recruitment: USA,Japan,Canada,Japan,Russia,Japan,Australia,Japan,New Zealand,Japan,Korea,Japan,Taiwan,Japan,China,Japan,Belgium,Japan,Czech Republic,Japan,Denmark,Japan,Finland,Japan,Germany,Japan,Hungary,Japan,Ireland,Japan,Israel,Japan,Italy,Japan,Netherlands,Japan,Norway,Japan,Poland,Japan,Spain,Japan,Sweden,Japan,Turkey,Japan,Ukraine,Japan,UK,Japan
• Study type: Interventional

Intervention(s)

- Participants receive pembrolizumab 400 mg via IV infusion on Day 1 of each 6-week cycle (Q6W) for up to 18 cycles (up to approximately 2 years).

- Participants receive a combination of paclitaxel 175 mg/m^2 on Day 1 of each 3-week cycle (Q3W) and carboplatin AUC 5 or 6 on Day 1 Q3W for 6 cycles (up to approximately 4 months). Participants who experience a severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel 75 mg/m^2 in place of paclitaxel on Day 1 Q3W after Sponsor consultation. Participants who experience a severe hypersensitivity reaction to carboplatin or an AE requiring discontinuation of carboplatin may receive cisplatin 75 mg/m^2 in place of carboplatin on Day 1 Q3W after Sponsor consultation.

Outcome(s)

Primary Outcome

- Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
- Overall Survival (OS)

Secondary Outcome

- Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR
- Disease Control Rate (DCR) per RECIST 1.1 as Assessed by BICR
- Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
- PFS per RECIST 1.1 as Assessed by Investigator
- Progression-Free Survival 2 (PFS2) per RECIST 1.1 as Assessed by Investigator
- Number of Participants Who Experience at Least One Adverse Event (AE)
- Number of Participants Who Discontinue Study Treatment Due to an AE
- Change From Baseline in European Organization for Research And Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS) (Item 29) And Quality of Life (QoL) (Item 30) Combined Score
- Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score
- Time to Deterioration (TTD) in EORTC QLQ-C30 GHS (Item 29) And QoL (Item 30) Combined Score
- TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Female

Include criteria

- Has a histologically confirmed diagnosis of Stage III or IV or recurrent Endometrial Carcinoma (EC) or carcinosarcoma (mixed Mullerian tumor) that is centrally confirmed as dMMR
- Has received no prior systemic therapy for advanced EC except for the following:
1.May have received prior radiation with or without radiosensitizing chemotherapy if >2 weeks before the start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (<=2 weeks of radiotherapy) to non-central nervous system (CNS) disease
2.May have received prior hormonal therapy for treatment of EC, provided that it was discontinued >=1 week prior to randomization
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization
- Is not pregnant or breastfeeding and agrees to not donate eggs and use a highly effective contraceptive method for 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapy if a woman of childbearing potential (WOCBP)
- Has a negative highly sensitive pregnancy test (urine or serum) within 24 hours for urine or 72 hours for serum before the first dose of study intervention if a WOCBP
- Provides an archival tumor tissue sample or newly obtained (core, incisional, or excisional) biopsy of a tumor lesion not previously irradiated for verification of dMMR status and histology
- Is Hepatitis B surface antigen (HBsAg) positive but has received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load prior to randomization
- Has a history of Hepatitis C virus (HCV) infection but has undetectable HCV viral load at screening

Exclude criteria

- Has uterine mesenchymal tumor such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas. Adenosarcomas and neuroendocrine tumors are not allowed
- Has EC of any histology that is proficient mismatch repair (pMMR)
- Is a candidate for curative-intent surgery or curative-intent radiotherapy
- 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 coinhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137])
- Has received prior systemic anticancer therapy including investigational agents for EC. This includes any chemotherapy given for EC other than as a radiosensitizer
- Has had a major operation and has not recovered adequately from the procedure and/or any complications from the operation before starting study intervention
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
- Is currently participating in or has participated in a study of an investigational agent for EC, has participated in a study of an investigational agent for non-EC within 4 weeks before the first dose of study intervention, or has used an investigational device within 4 weeks before the first dose of study intervention
- 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 intervention
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (excluding carcinoma in situ of the bladder) that have undergone potentially curative therapy are not excluded
- Has known active CNS metastases and/or carcinomatous meningitis
- Has a known intolerance to any study intervention and/or any of its excipients
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has an active infection, requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has had an allogenic tissue/solid organ transplant

Related Information

• Primary Sponsor: Hoki Toshifumi
• Secondary ID(s): NCT05173987