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 40 participants, 30 in the PM8002 (BNT327)+ chemotherapy regimen 1 group and 10 in the PM8002 (BNT327)+ chemotherapy regimen 2 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
Sponsors
BioNTech SE
Biotheus Inc.
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 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. |
| 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). |
| 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). |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| PD-L1 expression, CD8+ TIL, gene mutations | Up to approximately 2 years | PD-L1 expression in tumor and immune cells determined by IHC (immunohistochemistry), rate of CD8+ TIL determined by IHC, gene mutation type (including KRAS/NRAS/BRAF mutation) |
| Anti-drug antibody (ADA) | Up to 30 days after last treatment | the incidence of ADA to PM8002 |
| Pharmacokinetic (PK) parameters: maximum concentration | Up to 30 days after last treatment | Maximum plasma concentration \[Cmax\] derived from serum concentrations of PM8002(BNT327) after study drug administration. |
| Pharmacokinetic (PK) parameters: minimum concentration | Up to 30 days after last treatment | Minimum plasma concentration \[Cmin\] derived from serum concentrations of PM8002(BNT327) after study drug administration. |
Countries
China
Contacts
Primary ContactXuelian Xing
Outcome results
None listed