CRC (Colorectal Cancer)
Conditions
Brief summary
PM8002 (BNT327) is a bispecific antibody targeting PD-L1 and VEGF. This is a phase II trial to evaluate the efficacy and safety of PM8002 in combination with chemotherapy in first line MSS or MSI-L/pMMR metastatic colorectal cancer.
Detailed description
A multicenter, randomized, open-label study design is used, with a planned enrollment of 100 participants, 40 in the PM8002 (BNT327)+ chemotherapy regimen 1 group, 30 in the PM8002 (BNT327)+ chemotherapy regimen 2 group and 30 in the PM8002 (BNT327)+ chemotherapy regimen 3 group. The investigators make the decision on which chemotherapy regimen to be used in the participants. After combined chemotherapy regimen is confirmed, participants will be randomized to one of two dose levels of PM8002(BNT327) plus chemotherapy.
Interventions
DRUGPM8002
IV infusion
IV infusion
Oral administration and IV infusion
DRUGChemotherapy Regimen 3
IV infusion
Sponsors
Biotheus Inc.
BioNTech SE
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Signed informed consent form before any trial-related processes. 2. Age ≥ 18 years male or female. 3. Histologically or cytologically confirmed metastatic colorectal cancer (stage IV, UICC/AJCC staging system) that is not suitable for or cannot be radically resected surgically. 4. Participants must not have dMMR or MSI-H. 5. No prior systemic anti-tumor therapy for metastatic colorectal cancer. 6. have adequate organ function. 7. The investigator confirms at least one measurable lesion according to RECIST v1.1. A measurable lesion located in the field of previous radiation therapy or after local treatment may be selected as a target lesion if progression is confirmed. 8. The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1. Key
Exclusion criteria
1. Received the following treatments or medications prior to starting study treatment: 1. Received palliative local therapy, non-specific immunomodulatory therapy, or chineses herbal therapy with an anti-tumor indication within 14 days prior to study treatment. 2. Treatment with systemic glucocorticoids (prednisone \>10 mg/day or equivalent dose of other glucocorticoids) or other immunosuppressive agents within 14 days prior to initiation of study treatment. Note: treatment with local, intraocular, intra-articular, intranasal, and inhaled glucocorticosteroids and short-term prophylactic use of glucocorticoids (e.g., to prevent allergy to contrast agent) are allowed. 2. Have a major coagulation disorder or other evidence of significant bleeding risk. 3. Adverse effects of prior antitumor therapy have not returned to a CTCAE 5.0 grade rating of ≤ grade 1 4. Have a serious non-healing wound, ulcer, or bone fracture. 5. History of abdominal fistula, gastrointestinal perforation, or abdominal abscess, history of gastrointestinal obstruction, or clinical signs of gastrointestinal obstruction within 6 months prior to initiation of study treatment. 6. Severe uncontrollable intra-abdominal inflammation that requires clinical intervention, in the judgment of the investigator. 7. Have uncontrolled hypertension or poorly controlled diabetic conditions prior to study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to approximately 2 years | Objective response rate is the proportion of subjects with complete response (CR) or partial response (PR), based on RECIST v1.1. |
| Occurrence and severity of TEAE (treatment emergent adverse event), TRAE（treatment related adverse event）, TESAE (treatment emergent serious adverse event）, TRSAE (treatment related serious adverse event） | From the first dose of the investigational medicinal product (IMP) to the 30-day Safety Follow-Up Visit | AEs are graded according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0 in the combination treatment regimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DoR) | Up to approximately 2 years | DoR is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST v1.1) or death due to any cause, whichever occurs first. |
| Disease control rate (DCR) | Up to approximately 2 years | DCR is defined as the proportion of subjects with CR, PR, or stable disease(SD) based on RECIST v1.1. |
| Time to response (TTR) | Up to approximately 2 years | TTR is defined as the time from the start of the treatment to the first objective tumor response observed for patients who achieve CR or PR (based on RECIST v1.1). |
| Progression free survival (PFS) | Up to approximately 2 years | Progression free survival is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first (based on RECIST v1.1). |
| Overall survival (OS) | Up to approximately 5 years | OS is the time from the date of randomization or first dosing date to death due to any cause. |
Countries
China
Contacts
CONTACTXuelian Xing
PRINCIPAL_INVESTIGATORRuihua Xu, PhD, MD
Sun Yat-Sen University Cancer Center
Outcome results
None listed