Overview
This study is testing different dosing schedules of EMB-01 in patients with advanced colorectal cancer whose disease has recurrent or progressed on previous treatments. Patients will be randomly assigned to one of two dosing schedules: EMB-01 once weekly, or once weekly for 6 weeks then every two weeks.
Description
This is a randomized, open-label Phase II dose-optimization study of EMB-01 in patients with metastatic colorectal cancer (CRC). The study will enroll patients with recurrent/metastatic KRAS/BRAF wild-type left-sided CRC who have progressed, relapsed, or become intolerant after first- or second-line systemic therapy. Patients will be stratified by prior anti-EGFR therapy and randomized 1:1 into two groups.
Group 1 will receive EMB-01 1600 mg once weekly (QW). Group 2 will receive EMB-01 1600 mg QW for the first 6 weeks, followed by 1600 mg once every two weeks (Q2W).
Tumor assessments will follow RECIST v1.1 using CT and/or MRI. Baseline imaging will be performed within 28 days before enrollment. During the study, imaging and efficacy assessments will occur every 6 weeks for the first 12 cycles, and every 3 cycles thereafter. All imaging procedures must be consistent with baseline. Assessments will be performed by the investigator, with retrospective independent review if needed.
Eligibility
Inclusion Criteria:
- Able to understand and willing to sign the informed consent form (ICF).
- Male or female aged ≥ 18 years.
- Histologically or cytologically confirmed unresectable or metastatic left-sided colorectal cancer (primary tumor from splenic flexure to rectum) with at least one measurable lesion according to RECIST v1.1.
- ECOG performance status ≤ 1.
- Willing to provide a fresh tumor biopsy sample or a stored sample obtained within the past 2 years.
- Adequate organ function prior to the first study treatment.
- Prior anti-cancer treatment:
- Must have progressed on or been intolerant to at least first- or second-line systemic therapy for metastatic colorectal cancer. Prior therapy must include fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy, and bevacizumab with or without cetuximab. Patients should not have received TAS-102, fruquinitinib, or regorafenib.
- Any approved or investigational anti-cancer therapy (chemotherapy, immunotherapy, hormone therapy except for replacement therapy, testosterone, or oral contraceptives, biological therapy, targeted therapy) must be discontinued ≥ 4 weeks or 5 half-lives (whichever is shorter) before first study treatment.
- Palliative radiotherapy, bone metastasis radiotherapy, or oral fluoropyrimidines (e.g., tegafur, capecitabine) must be stopped ≥ 2 weeks before first study treatment; no therapeutic radiotherapy within 8 weeks before first EMB-01 dose.
- Women of childbearing potential or male patients with partners of childbearing potential must use one or more contraceptive methods from clinical screening and continue during study treatment until 3 months after the last EMB-01 dose.
Exclusion Criteria:
- Presence of KRAS/NRAS exon 2, 3, 4 mutations, BRAF V600 mutation, HER2 positivity (IHC3+ or amplification), dMMR/MSI-H, RET fusion, NTRK fusion, or other molecular mutations affecting anti-EGFR or cMET efficacy(Investigator and sponsor discussion recommended if applicable), based on central lab testing or prior treatment history.
- Life expectancy \< 3 months.
- Residual adverse events (AEs) from prior anti-cancer therapy \> CTCAE grade 1.
- Primary CNS malignancy or symptomatic CNS metastases (brain, leptomeningeal, or arachnoid). Patients with asymptomatic CNS metastases may be eligible if no local radiotherapy is needed, or radiotherapy was completed ≥ 4 weeks prior to study treatment.
- Pregnant or breastfeeding women.
- Major surgery within 28 days prior to screening. Surgical wounds must be fully healed.
- Idiopathic pulmonary fibrosis, unresolved active or chronic inflammatory lung disease, or history of interstitial lung disease (ILD). Patients with resolved radiation pneumonitis may be eligible.
- History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or severe skin infections.
- Prior dual anti-EGFR and cMET therapy.
- Prior EGFR inhibitor therapy discontinued due to severe skin toxicity.
- Other significant medical conditions, psychiatric or psychological disorders, or familial/endemically high-risk diseases that may interfere with study assessments, treatment, follow-up, adherence, or increase risk of treatment-related complications.
- Any condition deemed by the investigator to make study participation not in the patient's best interest or likely to interfere, limit, or confound study assessments.