EMB-01 dosing for recurrent or metastatic left-sided colorectal cancer

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

This trial tests two dosing schedules of EMB-01 in adults with recurrent or metastatic KRAS/BRAF wild-type left-sided colorectal cancer after first- or second-line treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai EpimAb Biotherapeutics Co., Ltd. (Industry-sponsored)
• Drugs / interventions: bevacizumab, cetuximab, fruquinitinib, chemotherapy, immunotherapy, radiation
• Locations: 2 sites (Beijing and 1 other locations)
• Trial ID: NCT07314294 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label Phase II dose-optimization trial comparing two EMB-01 dosing schedules in patients with recurrent or metastatic left-sided KRAS/BRAF wild-type colorectal cancer who progressed after first- or second-line systemic therapy. Patients are stratified by prior anti-EGFR therapy and randomized 1:1 to receive EMB-01 1600 mg once weekly or 1600 mg once weekly for six weeks followed by 1600 mg every two weeks. Tumor response is measured by RECIST v1.1 with baseline imaging within 28 days and on-study imaging every six weeks for the first 12 cycles, then every three cycles thereafter. Enrollment requires measurable disease, ECOG ≤1, and available tumor tissue (fresh or recent archived) or agreement between investigator and sponsor if biopsy is not feasible.

Who should consider this trial

Good fit: Adults (≥18) with unresectable or metastatic left-sided colorectal cancer that is KRAS/BRAF wild-type, who progressed on or were intolerant to first- or second-line therapy, have ECOG ≤1, and can provide tumor tissue are the intended candidates.

Not a fit: Patients with right-sided disease, known KRAS or BRAF mutations, poor performance status (ECOG ≥2), or who have not yet received or failed only first-line therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the study could identify a dosing schedule of EMB-01 that improves tumor control or tolerability for these patients.

How similar studies have performed: Dose-optimization and targeted approaches in select colorectal cancer populations have shown benefit in other programs, but EMB-01 itself is investigational with limited published efficacy data to date.

Eligibility criteria

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.

Where this trial is running

Beijing and 1 other locations

• Beijing Cancer Hospital — Beijing, China (Recruiting)
• The Sixth Affiliated Hospital of Sun Yat-Sen University — Guangzhou, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Mingfei Zhang

Conditions Metastatic Colorectal Cancer