Phase II Study of EMB-01 in Recurrent/Metastatic Colorectal Cancer Patients

A Randomized, Open-label, Phase II Study of EMB-01 in Patients With Recurrent/Metastatic Colorectal Cancer

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.

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.

Inclusion Criteria:

1. Able to understand and willing to sign the informed consent form (ICF).

2. Male or female aged ≥ 18 years.

3. 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.

4. ECOG performance status ≤ 1.

5. Willing to provide a fresh tumor biopsy sample or a stored sample obtained within the past 2 years.If no eligible archived tumor tissue sample is available and the patient's clinical condition is not suitable for biopsy, the patient may still be allowed to participate in screening upon confirmation and agreement between the investigator and the sponsor.

6. Adequate organ function prior to the first study treatment.

7. Prior anti-cancer treatment:

   1. 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.
   2. 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.
   3. Local radiotherapy, bone metastasis radiotherapy, or oral fluoropyrimidines (e.g., tegafur, capecitabine) must be stopped ≥ 2 weeks before first study treatment; therapeutic radiopharmaceuticals must not have been administered within 8 weeks prior to the first dose of EMB-01.

8. 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:

1. Presence of KRAS/NRAS exon 2, 3, 4 mutations, BRAF V600 mutation, HER2 positivity (IHC3+ or amplification), 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.
2. Life expectancy < 3 months.
3. Residual adverse events (AEs) from prior anti-cancer therapy > CTCAE grade 1.
4. 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.
5. Pregnant or breastfeeding women.
6. Major surgery within 28 days prior to screening. Surgical wounds must be fully healed.
7. 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.
8. History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or severe skin infections.
9. Prior dual anti-EGFR and cMET therapy or bispecific antibody-drug conjugates (ADCs).
10. Prior EGFR inhibitor therapy discontinued due to severe skin toxicity.
11. 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.
12. 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.