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OncoMatch/Clinical Trials/NCT05229003

Irinotecan Plus Anlotinib or Further in Combination With Penpulimab for Second-line Treatment of mCRC

Is NCT05229003 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Anlotinib and Penpulimab for metastatic colorectal cancer.

Phase 2RecruitingFudan UniversityNCT05229003Data as of May 2026

Treatment: Anlotinib · Penpulimab · IrinotecanThis is an exploratory, non-controlled, multi-cohort, phase II small-sample clinical study designed to evaluate the clinical benefit of second-line treatment with anlotinib plus irinotecan or further in combination with a PD-1 monoclonal antibody (penpulimab) in patients with advanced colorectal cancer after first-line treatment failure. To explore the rationality of the combination of chemotherapy and targeted therapy and immunotherapy strategy and obtain relevant survival and safety data. The study will fully evaluate the efficacy, PFS, OS, safety and related biomarkers of the regimen.

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Extracted eligibility criteria

Cancer type

Colorectal Cancer

Biomarker criteria

Required: KRAS any tested

the type of KRAS, NRAS, BRAF, and MSI were known

Required: NRAS any tested

the type of KRAS, NRAS, BRAF, and MSI were known

Required: BRAF wild-type

requiring wild type of BRAF

Required: MSH2 proficient mismatch repair

Cohort A required patients with MSS/pMMR status

Required: MSH6 proficient mismatch repair

Cohort A required patients with MSS/pMMR status

Required: MLH1 proficient mismatch repair

Cohort A required patients with MSS/pMMR status

Required: PMS2 proficient mismatch repair

Cohort A required patients with MSS/pMMR status

Disease stage

Metastatic disease required

Performance status

ECOG 0–1(Restricted strenuous activity)

Prior therapy

Max 1 prior line
Min 1 prior line

Must have received: platinum-based chemotherapy (oxaliplatin) — first-line

The patient received oxaliplatin in combination with fluorouracil as the first-line systemic therapy (with or without anti-EGFR mab or VEGF mab) and failed. Fluorouracil (5-FU, capecitabine, or S-1) and oxaliplatin must be included in the first-line regimens.

Must have received: antimetabolite (fluorouracil, capecitabine, S-1) — first-line

Fluorouracil (5-FU, capecitabine, or S-1) and oxaliplatin must be included in the first-line regimens.

Cannot have received: topoisomerase inhibitor (irinotecan)

Former treatment of irinotecan for 1 or more cycles

Cannot have received: anti-VEGFR small molecule inhibitor (apatinib, regorafenib, fruquintinib, anlotinib)

Prior exposure to any anti-VEGFR small molecule inhibitors (e.g. Apatinib, regorafenib, Fruquintinib, Anlotinib, etc.)

Cannot have received: anti-PD-1 therapy

Prior exposure to any anti-PD-1 or anti-PD-L1, PD-L2, CD137, CTLA-4 antibody therapy, or any other antibody or drug that specifically targets T-cell costimulation or immune checkpoint pathways

Lab requirements

Blood counts

ANC ≥1.5x10^9/L; Hemoglobin ≥8.0g/dL; Platelet count ≥80x10^9/L

Kidney function

Serum creatinine ≤1 x ULN, the clearance rate of endogenous creatinine >50ml/min

Liver function

Total bilirubin < 1.5x ULN; ALT and AST < 2.5x ULN (with liver metastasis <5x ULN)

Cardiac function

No coronary heart disease of grade I or above, arrhythmia of grade I or above (including prolonged QTc interval >450ms in males and >470ms in females), and cardiac dysfunction of grade I or above

Bone marrow capacity and liver and kidney function were sufficiently reserved within 7 days before screening: absolute neutrophil (ANC) count ≥1.5x109 /L; Hemoglobin ≥ 8.0g/ dL; Platelet count ≥80 x109 /L; Total bilirubin < 1.5 times upper normal limit (ULN); ALT and AST< 2.5x ULN (with liver metastasis <5x ULN); Serum creatinine ≤1 x ULN, the clearance rate of endogenous creatinine >50ml/min

Structured fields extracted by AI. May contain errors — verify against the official protocol.

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