A Phase III, Randomized, Controlled and Multi-center Study of AK112 and Chemotherapy in First-line Metastatic Colorectal Cancer

Phase 3

Not yet recruiting

• Conditions: Colorectal Adenocarcinoma
• Interventions: Drug: AK112; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin and 5-FU; Drug: Bevacizumab

• Registration Number: NCT06951503
• Lead Sponsor: Akeso

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-23
• Study First Submitted QC: 2025-04-23
• Last Update Submitted: 2025-04-23
• Study First Posted: 2025-04-30
• Last Update Posted: 2025-04-30
• Study Start: 2025-05-09
• Primary Completion: 2027-01-13
• Study Completion: 2029-01-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 560

Inclusion Criteria

1. Signed informed consent.
2. Age ≥ 18 years and ≤ 75 years.
3. ECOG status of 0 or 1.
4. Estimated survival ≥ 3 months.
5. Subjects with histologically or cytologically confirmed metastatic colorectal adenocarcinoma.
6. 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.
7. At least one measurable disease based on RECIST v1.1.
8. Adequate organ function per protocol-defined criteria.
9. 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.

Exclusion Criteria

1. Previous (within 3 years) or concurrent other malignant tumors, excluding those that have been cured.
2. Participating in other interventional study within 4 weeks prior to the first study drug administration.
3. 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.
4. Current presence of uncontrolled combined disease.
5. Active clinical infections.
6. History of severe bleeding tendency or coagulation dysfunction.
7. Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection.
8. Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study.
9. Current presence of significant radiographic or clinical manifestations of GI obstruction.
10. Toxicities of prior anticancer therapy have not resolved to ≤ Grade 1 (NCI-CTCAE version 5.0).
11. Pregnant or lactating women.
12. Any condition considered by the investigator to be inappropriate for enrollment.
13. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AK112 in combination with FOLFOXIRI	AK112	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.
AK112 in combination with FOLFOXIRI	Oxaliplatin	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.
AK112 in combination with FOLFOXIRI	Irinotecan	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.
AK112 in combination with FOLFOXIRI	Leucovorin and 5-FU	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.
Bevacizumab in combination with FOLFOXIRI	Oxaliplatin	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 .
Bevacizumab in combination with FOLFOXIRI	Irinotecan	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 .
Bevacizumab in combination with FOLFOXIRI	Leucovorin and 5-FU	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 .
Bevacizumab in combination with FOLFOXIRI	Bevacizumab	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 .

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) assessed by blinded independent central review (BICR)	Up to approximately 3 years	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).

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DoR)	Up to approximately 3 years	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression(based on RECIST v1.1 criteria) or death due to any cause, whichever occurs first.
Overall survival (OS)	Up to approximately 5 years	OS is defined as the time from randomization to death due to any cause.
Progression-free survival (PFS) assessed by investigator	Up to approximately 3 years	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).
Objective Response Rate (ORR)	Up to approximately 3 years	ORR is defined as proportion of subjects who have a complete or partial response relative to baseline according to RECIST 1.1 criteria.
Disease control rate (DCR)	Up to approximately 3 years	DCR is defined as the proportion of subjects with CR, PR, or SD (based on RECIST v1.1 criteria).

Trial Locations

Locations (2)

The Sixth Hospital,Sun Yat-sen University; 🇨🇳 Guanzhou, Guangdong, China

Sun Yat-sen University Cancer Center; 🇨🇳 Guanzhou, Guangdong, China