First-line pMMR Endometrial Cancer
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo controlled Phase III clinical trial, aiming to evaluate the efficacy and safety of HB0025 combined with chemotherapy (paclitaxel plus carboplatin) versus placebo combined with chemotherapy (paclitaxel plus carboplatin) as a first-line treatment for advanced (Stage III/IV) or recurrent proficient Mismatch Repair Endometrial Cancer（pMMR EC). The trial will take progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) as the primary endpoint, and plans to enroll approximately 333 participants. After being eligible for screening, participants will be randomly assigned to the study arms at a ratio of 2:1 to receive either HB0025 combined with chemotherapy (experimental group) or placebo combined with chemotherapy (control group). Both regimens will be administered once every 3 weeks (Q3W). After completing 6 cycles of combination treatment, patients will enter the maintenance therapy phase with HB0025 or placebo (Q3W) only. The treatment will last until intolerable toxicity occurs, disease progression, lost to follow up or death, withdrawal of consent, pre-scheduled study treatment are completed, receiving new anticancer therapy or sponsor discontinue the study, whichever comes first.
Interventions
DRUGHB0025 Injection
20mg/kg, ivgtt, Q3W, developed by Sponsor Huaota
DRUGPaclitaxel injection
175mg/m\^2, Q3W
DRUGCarboplatin injection
AUC5, Q3W
OTHERPlacebo matching HB0025
Participants will be administered placebo matching HB0025
Sponsors
Shanghai Huaota Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female patients aged 18 years or older at screening. 2. Able to fully understand and voluntarily sign the informed consent form, and are willing and able to follow the clinical trial and subsequent visit procedures. 3. Patients diagnosed with advanced (stage III/IV, classified according to the 2009 International Federation of Gynecology and Obstetrics (FIGO)) or recurrent endometrial cancer, whose pathological type include but are not limited to endometrial adenocarcinoma, serous carcinoma, clear cell carcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, mixed carcinoma, carcinosarcoma (excluding uterine sarcoma), and confirmed as pMMR in the central laboratory. 4. Patients who had not received any systemic anti-tumor treatment for endometrial cancer in the past and are not suitable for radical surgical resection and/or radical concurrent radiotherapy. 5. Agree and can provide sufficient and qualified tumor tissue samples from the primary site or metastatic site (either archived tissue samples from the past 3 years before randomization or fresh tissue samples) for the detection of MMR and PD-L1 status. 6. ECOG PS of 0-1. 7. Adequate organ function.
Exclusion criteria
1. Second primary malignancy within 5 years before screening. 2. Brain metastases accompanied by central nervous system symptoms. 3. Previously treated with immune checkpoint inhibitors and/or anti-angiogenic drugs. 4. Those who underwent surgery within 4 weeks before the first treatment , or suffered from major traumatic injuries, or were judged by the researchers to have not fully recovered from previous surgeries, or were expected to require surgery during the study period. 5. Arterial hypertension that remains uncontrolled even after receiving standard treatment (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg). 6. Those who have had or currently have interstitial lung disease, pneumoconiosis, drug-related pneumonia, or severely impaired lung function, which may interfere with the detection and management of suspected drug-related pulmonary toxicity. 7. Pregnant or lactating women. 8. Known psychiatric disorder, alcoholism, drug addiction or substance abuse. 9. Participant who, in the opinion of the investigator, are unsuitable to participate in this trial for any other reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to 34 months | PFS is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the Blinded Independent Central Review or death due to any cause (whichever occurs first) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to 34 months | PFS is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first) |
| Objective Response Rate (ORR) | Up to 34 months | ORR is defined as the proportion of subjects achieving the best overall response (BOR) as complete response (CR) or partial response (PR) according to RECIST 1.1 by investigator or Blinded Independent Central Review. |
| Disease control rate (DCR) | Up to 34 months | DCR defined as the number of patients were confirmed CR or PR or stable disease(SD) according to RECIST 1.1 by investigator or Blinded Independent Central Review divided by the patients with at least one tumour evaluation. |
| Duration of response (DOR) | Up to 34 months | DOR is defined as the time from the first record of CR or PR to the first record of disease progression as evaluated by investigators or Blinded Independent Central Review according to RECIST v1.1 or death. |
| Time to Progression(TTP) | Up to 34 months | TTP is defined as the time from the time of randomization to the occurrence of disease progression according to Recist 1.1 by investigator or Blinded Independent Central Review. |
| Overall Survival (OS) | Up to 34 months | OS is defined as the period from the start of randomization to the time of death due to any cause. |
| Safety Assessment | Up to 34 months | The incidence, severity and outcome of adverse events (AE), serious adverse events (SAE), immune-related adverse events (irAE) and adverse events of special interest (AESI) per NCI-CTCAE V6.0. |
| Cmax | Up to 34 months | Peak Plasma Concentration |
| AUC | Up to 34 months | Area under the plasma concentration versus time curve |
| ADA titer | Up to 34 months | titer of anti-drug antibody |
Countries
China
Outcome results
None listed