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

Akeso

Status and phase: Not yet enrolling; Phase 3

Conditions: Colorectal Adenocarcinoma

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06951503

AK112-312

Details and patient eligibility

About

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.

Enrollment: 560 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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560 participants in 2 patient groups

AK112 in combination with FOLFOXIRI

Experimental group

Description:

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.

Treatment:

Drug: Irinotecan

Drug: Oxaliplatin

Drug: Leucovorin and 5-FU

Drug: AK112

Bevacizumab in combination with FOLFOXIRI

Active Comparator group

Description:

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 .

Treatment:

Drug: Irinotecan

Drug: Oxaliplatin

Drug: Leucovorin and 5-FU

Drug: Bevacizumab