This is an open-label, multicenter, Phase Ib trial designed to evaluate the safety, tolerability, and preliminary efficacy of EMB-01 in combination with chemotherapy in patients with unresectable or metastatic colorectal cancer (CRC), and to determine the recommended Phase II combination dose (RP2CD). The study consists of a dose escalation phase followed by a dose expansion phase. Approximately 30 patients are planned to be enrolled in each combination treatment group across both phases, with a maximum total enrollment of approximately 120 patients.

Inclusion Criteria:

• 1. Male or female patients aged ≥ 18 and < 75 years. 2. Histologically or cytologically confirmed unresectable or metastatic left-sided colorectal cancer (primary tumor located from the splenic flexure to the rectum), with measurable disease per RECIST v1.1.

  3. ECOG performance status ≤ 1. 4. Agrees to provide archival tumor tissue (formalin-fixed paraffin-embedded, collected within 18 months) or newly obtained biopsy tissue. If no eligible archival tissue is available and the patient's clinical condition is not suitable for biopsy, the patient may be screened after confirmation and agreement between the investigator and sponsor.

  5. Adequate organ function within 14 days prior to the first dose of study treatment 6. Prior anti-tumor therapy:

  1. Patients who received any approved or investigational anti-cancer therapy must have discontinued such therapy at least 4 weeks prior to the first dose of study treatment or 5 half-lives of the agent, whichever is shorter.

  2. Patients who received local radiotherapy, bone metastasis radiotherapy, or oral fluoropyrimidines must have discontinued such therapy at least 2 weeks prior to the first dose of study treatment. No therapeutic radiopharmaceuticals within 8 weeks prior to the first dose of EMB-01.

     Prior anti-tumor therapy requirements by combination regimen*:

• Arm A (irinotecan) and Arm B (TAS-102): Prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, plus prior anti-VEGF therapy (with or without anti-EGFR therapy), with disease progression or intolerance; no prior TAS-102/fruquintinib/regorafenib. If prior anti-EGFR therapy was received, the patient must have achieved CR, PR, or SD, with the last anti-EGFR dose administered at least 4 months prior to the first study drug dose.

• Arm C (mFOLFOX6): No prior oxaliplatin-based chemotherapy and no prior anti-EGFR therapy.

• Arm D (FOLFIRI): No prior irinotecan-based chemotherapy and no prior anti-EGFR therapy.

  7. Female patients of childbearing potential or male patients with partners of childbearing potential must use one or more contraceptive methods from the screening period, continue such methods during study treatment, and until 3 months after the last dose of EMB-01 (for Arm B: 6 months after last TAS-102 dose for both sexes; for Arm C: 9 months after last oxaliplatin dose for females, 6 months for males; for Arm A/D: 6 months after last chemotherapy dose for females, 3 months for males).

  8. Able to swallow and retain oral medications, and has adequate venous access.

Exclusion Criteria:

• 1. Expected survival < 3 months. 2. Presence of KRAS/NRAS (exons 2, 3, 4), BRAF V600, HER2 positivity (IHC3+ and/or amplification), RET/NTRK fusion, or other molecular alterations that may affect anti-EGFR or cMET therapy efficacy, as detected by central laboratory testing at screening or documented in prior treatment history. (Discussion between investigator and sponsor in writing is recommended if applicable.) 3. Persistent adverse events (AEs) from prior anti-tumor therapy > Grade 2 per CTCAE v5.0, except alopecia, Grade 2 fatigue, or Grade 2 peripheral neuropathy.

  4. Primary central nervous system (CNS) malignancy or symptomatic CNS/leptomeningeal metastases. Asymptomatic CNS metastases are allowed if no local radiotherapy is required, or if radiotherapy was completed ≥ 4 weeks prior to first study dose.

  5. Prior treatment with anti-EGFR × cMET bispecific antibody or bispecific ADC. 6. Discontinuation of EGFR inhibitors due to skin toxicity. 7. History of life-threatening hypersensitivity, or known allergy to recombinant proteins/excipients in EMB-01 or any study treatment contraindication.

  8. Systemic corticosteroids (> 10 mg prednisone equivalent/day) or other immunosuppressants required within 14 days prior to first dose, regardless of autoimmune disease. Inhaled/topical/ocular/nasal/joint steroids are permitted; adrenal replacement steroids are allowed at >10 mg/day if no active autoimmune disease.

  9. Severe/uncontrolled cardiac disease requiring treatment 10. Use or planned use of QT-prolonging or rhabdomyolysis-inducing drugs during screening through study end (only Arm C); or known CYP3A4/UGT1A1 strong inhibitors/CYP3A4 inducers/anticholinesterase neuromuscular blockers (only Arms A/D).

  10. Rare hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (only Arm B).

  11. Other serious uncontrolled medical, psychiatric, or familial/endemic conditions that may interfere with study assessments, adherence, or safety (investigator's assessment).

  12. Any condition that, in the investigator's opinion, makes study participation not in the patient's best interest or confounds study evaluations.