Unresectable Advanced or Metastatic Colorectal Cancer
Conditions
Brief summary
This study constitutes an open-label, multi-cohort, multi-center Phase Ib/II clinical study, developed to assess the safety, tolerability, and therapeutic efficacy of SYS6090 injection when administered in combination with bevacizumab, or in triple combination with bevacizumab and chemotherapy, among patients diagnosed with advanced colorectal cancer.
Interventions
DRUGSYS6090 (Fixed Dose Level A) + bevacizumab
Participants will receive intravenous SYS6090 at fixed dose level A combined with intravenous bevacizumab, administered per cycle schedule specified in study protocol, for advanced/palliative unresectable pMMR/MSS colorectal cancer.
DRUGSYS6090 (Fixed Dose Level B ) + bevacizumab
Participants will receive intravenous SYS6090 at fixed dose level B plus intravenous bevacizumab per protocol-defined cycle schedule for unresectable advanced pMMR/MSS colorectal cancer.
DRUGSYS6090 RP2D + bevacizumab +mFOLFOX6
Participants will receive intravenous SYS6090 at RP2D plus intravenous bevacizumab combined with standard mFOLFOX6 chemotherapy regimen (oxaliplatin, leucovorin, fluorouracil), administered per protocol-defined cycle schedule for unresectable advanced pMMR/MSS colorectal cancer.
DRUGSYS6090 RP2D + bevacizumab
Participants will receive intravenous SYS6090 at RP2D plus intravenous bevacizumab, administered per protocol-defined cycle schedule for unresectable advanced pMMR/MSS colorectal cancer.
DRUGRegorafenib
Oral regorafenib monotherapy as standard control for metastatic pMMR/MSS colorectal cancer.
DRUGSYS6090 PR2D+ bevacizumab + FOLFOXIRI
Participants will receive intravenous SYS6090at RP2D plus intravenous bevacizumab combined with FOLFOXIRI triple chemotherapy (oxaliplatin, irinotecan, leucovorin, fluorouracil) per study cycle schedule for metastatic pMMR/MSS colorectal cancer.
DRUGbevacizumab + FOLFOXIRI
Participants will receive intravenous bevacizumab combined with FOLFOXIRI triple chemotherapy (oxaliplatin, irinotecan, leucovorin, fluorouracil) per study cycle schedule for metastatic pMMR/MSS colorectal cancer.
Sponsors
CSPC Megalith Biopharmaceutical Co.,Ltd.
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
\*Eligibility Criteria: Inclusion Criteria: 1. Subjects must be ≥18 years of age. 2. Histologically or cytologically confirmed unresectable advanced or metastatic colorectal cancer with pMMR/MSS status, assigned to corresponding cohorts as follows: Cohort 1 (2L/3L) of Phase Ib \& Phase II: Subjects must have disease progression after no more than 2 lines of standard systemic therapy (prior regimens must contain fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy); tumor tissue confirmed as pMMR by IHC or MSS by NGS/PCR; Cohort 2 (1L) of Phase Ib \& Phase II: Subjects have received no prior systemic anti-tumor therapy for advanced disease; tumor tissue confirmed as pMMR by IHC or MSS by NGS/PCR. 3. At least one extracranial measurable lesion at baseline according to RECIST 1.1 criteria. 4. Eastern Cooperative Oncology Group performance status of 0 or 1. 5. Expected survival ≥ 3 months. 6. Has protocol-defined adequate organ and bone marrow function.
Exclusion criteria
1. Subjects with clinically active central nervous system metastases; 2. with a history of other primary malignant tumors within 5 years before administration; 3. Subjects assigned to Cohort 1 who have received prior regorafenib treatment.; 4. Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening; 5. Uncontrolled or significant cardiovascular disease; 6. Clinically uncontrolled pleural effusion, ascites or pericardial effusion; 7. Has unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to Grade ≤ 1 or baseline .
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose (RP2D), Safety and Tolerability | up to approximately 3 years after the first enrollment | RP2D of SYS6090 combination therapy,Safety and tolerability are evaluated via incidence and severity of all Adverse Events (AEs) and Serious Adverse Events (SAEs) graded per NCI-CTCAE version 6.0, including abnormal laboratory tests, ECG parameters and vital signs from screening through end of safety follow-up. |
| Objective Response Rate (ORR) assessed per RECIST v1.1 | up to approximately 3 years after the first enrollment | ORR per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by investigator was defined as the percentage of participants with at least one visit confirmed complete response (CR) or partial response (PR), for all cohorts in Phase Ib and Cohort 1 of Phase II expansion stage. |
| Progression-Free Survival (PFS) assessed per RECIST v1.1 | up to approximately 3 years after the first enrollment | PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by investigator was defined as the time from the date of randomization or first study treatment until the date of confirmed progressive disease (PD), or death by any cause in the absence of progression, regardless of whether the participant withdrew from study therapy or received another anticancer therapy prior to progression, for Cohort 2 of Phase II expansion stage. |
Countries
China
Contacts
CONTACTClinical Trials Information Group officer
CONTACTLIN
Outcome results
None listed