AK112 Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI as Second-line Treatment of MSS/pMMR Metastatic Colorectal Cancer

NCT07021950 | Not Yet Recruiting Phase 2

• 1 other identifier: AK112-CRC
• Study Type: interventional
• Target: 130
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a multicenter, open-label phase II trial conducted to assess the safety and antitumor activity of Ivonescimab (AK112) plus FOLFIRI versus bevacizumab plus FOLFIRI as second-line treatment in subjects with MSS/pMMR metastatic colorectal cancer who have experienced intolerance to oxaliplatin-containing first-line therapy or disease progression, or recurrence within 6 months after oxaliplatin adjuvant therapy.

Conditions

Colorectal Cancer; Ivonescimab

Outcome Measures

Primary Outcomes (1)

• PFS

  Refers to the date from the date of admission to the date of the first progression of disease or death of any cause, using Response Evaluation Criteria in Solid Tumors version 1.1(RECIST v1.1)

  up to 24 months

Secondary Outcomes (5)

• ORR

  up to 24 months

• DCR

  up to 24 months

• DoR

  up to 24 months

• OS

  up to 3 years

• AE

  up to 36 months untill study complete

Study Arms (2)

AK112+FOLFIRI

EXPERIMENTAL

experimental group receives AK112 at 20 mg/kg via intravenous infusion on day 1 of each cycle (Q2W) combined with FOLFIRI chemotherapy (Q2W)

Drug: AK112; Drug: FOLFIRI

bevacizumab+FOLFIRI

ACTIVE COMPARATOR

Control group receives bevacizumab at 5 mg/kg via intravenous infusion on day 1 of each cycle (Q2W) combined with FOLFIRI chemotherapy (Q2W)

Drug: FOLFIRI; Drug: Bevacizumab

Interventions

AK112 DRUG

AK112：20mg/kg，Q2W。Administered over 60 minutes (±10 minutes). For intolerable cases, infusion duration may extend up to 120 minutes. During treatment, dosing delays are allowed for up to 12 weeks (calculated from the last dose). AK112 may be resumed after 12 weeks under the following conditions: If treatment is paused due to glucocorticoid tapering for managing immune-related adverse events (irAEs);If treatment is paused due to adverse events unrelated or deemed unrelated to AK112; Resumption is permitted only if the investigator judges continued therapy beneficial, following discussion with relevant medical personnel.

Also known as: Ivonescimab

AK112+FOLFIRI

FOLFIRI DRUG

FOLFIRI：Irinotecan, 180 mg/m² IV over 30-90 minutes (Day 1); Leucovorin (LV), 400 mg/m² IV over 2 hours (Day 1); 5-FU, 400mg/m²IV Day1, then 1200 mg/(m².d) ×2 days (total 2400 mg/m² ,IV over 46-48 hours).Q2W.

AK112+FOLFIRI; bevacizumab+FOLFIRI

Bevacizumab DRUG

Bevacizumab：5 mg/kg，Q2W. The initial intravenous infusion should last approximately 90 minutes. If the first infusion is well tolerated, the duration of the second infusion can be reduced to approximately 60 minutes. Should the participant also tolerate the 60-minute infusion well, then all subsequent infusions may be administered over a period of approximately 30 minutes. Continuous monitoring for potential infusion-related reactions during the drip is required; if an infusion-related reaction occurs, the infusion rate should be promptly reduced or the infusion temporarily halted.

bevacizumab+FOLFIRI

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign written informed consent
• Agree to provide tumor and blood samples for biomarker detection
• Age ≥18 and ≤75 years at enrollment, regardless of gender
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Expected survival ≥3 months
• Pathologically confirmed locally advanced unresectable or metastatic colorectal adenocarcinoma
• Confirmed MSS/pMMR-type CRC by immunohistochemistry (IHC), PCR, or NGS
• Intolerance to oxaliplatin-containing standard first-line therapy, disease progression, or recurrence within \< 6 months after oxaliplatin adjuvant therapy
• Adequate organ function (last 14 days without intervention):
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L without granulocyte colony-stimulating factor1.
• Platelets ≥100×10⁹/L without transfusion1.
• Hemoglobin \>9 g/dL without transfusion or erythropoietin1.
• Total bilirubin ≤1.5×ULN1.
• AST/ALT ≤2.5×ULN1.
• Serum creatinine ≤1.5×ULN and creatinine clearance (Cockcroft-Gault) ≥60 mL/min1.

Sponsors & Collaborators

• Sun Yat-sen University: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

IFL protocol; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ruihua Xu, MD, PhD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruihua Xu, MD,phD

CONTACT

+86 13922206676; xurh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: June 15, 2025
• Study Start: August 10, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 15, 2025

Record last verified: 2025-06