Table 1 Eligibility criteria for the PURSUIT trial

1. Unresectable colorectal cancer pathologically diagnosed as adenocarcinoma

2. RAS (KRAS/NRAS) and BRAF V600E wild-type in tumor tissue sample

3. Patients intolerant or refractory to chemotherapy, including fluoropyrimidine, oxaliplatin, and irinotecan

4. Complete or partial response to previous chemotherapy, including anti-EGFR mAb (cetuximab or panitumumab) according to RECIST version 1.1

5. Documentation of progression to previous anti-EGFR therapy within 2 months after last anti-EGFR mAb administration

6. Patients negative for RAS mutations in ctDNA using OncoBEAM RAS CRC kit within 28 days before enrollment in the REMARRY study

7. Four months or more between the last administration of previous anti-EGFR mAbs and the start of protocol treatment

8. Measurable disease according to RECIST version 1.1

9. ECOG PS 0 or 1

10. Age 20 years or older

11. Adequate major organ function assessed within 14 days before enrollment:

a. Neutrophil count ≥1500/mm3

b. Platelet count ≥75,000/mm3

c. Hemoglobin ≥9.0 g/dL

d. ALT and AST ≤100 IU/L (≤ 200 IU/L for patients with liver metastasis)

e. Serum creatinine ≤1.5 mg/dL

12. Life expectancy of at least 12 weeks

13. Written informed consent obtained

1. Severe comorbidity.

a. Synchronous active malignancies

b. Uncontrolled brain metastasis or leptomeningeal metastasis

c. Active infectious disease

d. Uncontrolled ascites, pleural effusion, or pericardial effusion requiring continued drainage

e. Uncontrolled diabetes mellitus or hypertension

f. Myocardial infarction, severe/unstable angina pectoris, symptomatic congestive heart failure of New York Heart Association Class III or IV within 6 months before the enrollment

g. Psychiatric diseases or psychiatric symptoms considered as difficult to enroll in a clinical trial

2. Underwent one of following treatments before protocol treatment:

a. Extensive surgery within 4 weeks

b. Colostomy/ileostomy within 2 weeks

c. Chemotherapy within 2 weeks

d. Radiation therapy within 2 weeks

3. CTCAE Grade ≥ 2 adverse events due to previous therapy, which are not recovered

4. History of severe infusion reactions to anti-EGFR mAbs

5. Intolerant to previous irinotecan therapy

6. Comorbidity or history of severe pulmonary disease

7. Men/women who are unwilling to avoid pregnancy; women who are pregnant or breastfeeding; women with a positive pregnancy test

8. Known active HCV or HIV infection

9. Any other patients who are regarded as inadequate for trial enrollment by investigators