AK112 and Chemotherapy in First-line Metastatic Colorectal Cancer

NCT06951503 | Recruiting Phase 3 DMC

• 1 other identifier: AK112-312
• Study Type: interventional
• Target: 560
• Locations: 1 country
• Sites: 2

Brief Summary

This trial is a Phase III study. The purpose of this study is to evaluate the efficacy and safety of AK112 and chemotherapy versus bevacizumab and chemotherapy for the first-line treatment of metastatic colorectal cancer.

Conditions

Colorectal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) assessed by blinded independent central review (BICR)

  PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first (based on RECIST 1.1 criteria).

  Up to approximately 3 years

Secondary Outcomes (5)

• Overall survival (OS)

  Up to approximately 5 years

• Progression-free survival (PFS) assessed by investigator

  Up to approximately 3 years

• Objective Response Rate (ORR)

  Up to approximately 3 years

• Duration of Response (DoR)

  Up to approximately 3 years

• Disease control rate (DCR)

  Up to approximately 3 years

Study Arms (2)

AK112 in combination with FOLFOXIRI

EXPERIMENTAL

AK112 in combination with FOLFOXIRI (Irinotecan, Oxaliplatin, Leucovorin and 5-FU) for induction treatment. Later, patients will receive maintenance Leucovorin and 5-FU plus AK112.

Drug: AK112; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin and 5-FU

Bevacizumab in combination with FOLFOXIRI

ACTIVE COMPARATOR

Bevacizumab in combination with FOLFOXIRI (Irinotecan, Oxaliplatin, Leucovorin and 5-FU) for induction treatment. Later, patients will receive maintenance Leucovorin and 5-FU plus Bevacizumab .

Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin and 5-FU; Drug: Bevacizumab

Interventions

AK112 DRUG

iv, q2w

AK112 in combination with FOLFOXIRI

Oxaliplatin DRUG

iv, q2w

AK112 in combination with FOLFOXIRI; Bevacizumab in combination with FOLFOXIRI

Irinotecan DRUG

iv, q2w

AK112 in combination with FOLFOXIRI; Bevacizumab in combination with FOLFOXIRI

Bevacizumab DRUG

iv, q2w

Bevacizumab in combination with FOLFOXIRI

Leucovorin and 5-FU DRUG

iv, q2w

AK112 in combination with FOLFOXIRI; Bevacizumab in combination with FOLFOXIRI

Eligibility Criteria

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

You may qualify if:

• Signed informed consent.
• Age ≥ 18 years and ≤ 75 years.
• ECOG status of 0 or 1.
• Estimated survival ≥ 3 months.
• Subjects with histologically or cytologically confirmed metastatic colorectal adenocarcinoma.
• Subjects who are not candidates for radical surgical resection or local therapy and have not received systemic anti-tumor therapy in the recurrent or metastatic setting. Subjects who have received prior neoadjuvant or adjuvant therapy and whose first discovery of recurrence or metastases is ≥ 12 months after the last dose of neoadjuvant or adjuvant therapy are allowed to enroll.
• At least one measurable disease based on RECIST v1.1.
• Adequate organ function per protocol-defined criteria.
• Women of childbearing potential and men with female partners of childbearing potential must agree to use effective contraception during treatment and for at least 180 days following the last dose of study treatment.

You may not qualify if:

• Previous (within 3 years) or concurrent other malignant tumors, excluding those that have been cured.
• Participating in other interventional study within 4 weeks prior to the first study drug administration.
• Palliative local treatment for non-target lesions within 2 weeks prior to the first administration; received non-specific immunomodulatory therapy within 2 weeks prior to the first administration.
• Current presence of uncontrolled combined disease.
• Active clinical infections.
• History of severe bleeding tendency or coagulation dysfunction.
• Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection.
• Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study.
• Current presence of significant radiographic or clinical manifestations of GI obstruction.
• Toxicities of prior anticancer therapy have not resolved to ≤ Grade 1 (NCI-CTCAE version 5.0).
• Pregnant or lactating women.
• Any condition considered by the investigator to be inappropriate for enrollment.
• Local or systemic disease caused by non-malignancy, or disease or symptom secondary to tumor, that can lead to higher medical risk and/or uncertainty in survival.

Sponsors & Collaborators

• Akeso: lead

Study Sites (2)

The Sixth Hospital,Sun Yat-sen University

Guanzhou, Guangdong, 510000, China

RECRUITING

Sun Yat-sen University Cancer Center

Guanzhou, Guangdong, China

RECRUITING

MeSH Terms

Interventions

Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil; Bevacizumab

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Xufang Yu, MD

CONTACT

+86(0760)89873999; clincialtrails@akesobio.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2025
• First Posted: April 30, 2025
• Study Start: May 27, 2025
• Primary Completion (Estimated): January 13, 2027
• Study Completion (Estimated): January 7, 2029
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

CN (2)