A Prospective, Single Arm, Open Label, Phase II Clinical Study on the Efficacy and Safety of Ivonescimab (AK112) Combined With TAS-102 in the Treatment of Refractory MSS/pMMR Advanced Colorectal Cancer

A Prospective, Single Arm, Open Label, Phase II Clinical Study on the Efficacy and Safety of Ivonescimab (AK112) Combined With TAS-102 in the Treatment of Refractory MSS/pMMR Advanced Colorectal Cancer

Main purpose:

Evaluate the efficacy and safety of the combination therapy of Ivonescimab (AK112) and TAS-102 in the treatment of refractory MSS/pMMR advanced colorectal cancer

Exploratory purpose:

Evaluation of the relationship between immune markers, patient efficacy, and prognosis in the treatment of refractory MSS/pMMR advanced colorectal cancer with the combination of Ivonescimab (AK112) and TAS-102 Study endpoint

Primary endpoint:

Researchers evaluated the PFS rate at 18 weeks based on RECIST v1.1.

Secondary endpoint:

ORR, DCR, PFS, and OS evaluated based on RECIST v1.1. The incidence and severity of adverse events (AEs)

Study Overview

• Status: Enrolling by invitation
• Conditions: MSS/pMMR Type Metastatic Colorectal Adenocarcinoma Patients
• Intervention / Treatment: Drug: Ivonescimab,TAS-102

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Huai'an,, Jiangsu, China, 210000
      • The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University#Huai'an First People's Hospital#

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18 years old and above but 75 years old and below, regardless of gender;

2. Previously received at least two standard chemotherapy regimens for advanced colorectal cancer and demonstrated disease progression or intolerance to the last regimen.

   Patients who have received adjuvant/neoadjuvant chemotherapy and experience recurrence during or within 6 months after completion of adjuvant/neoadjuvant chemotherapy can be considered as a chemotherapy regimen for advanced disease;

3. There are sufficient tissue specimens that have been tested as pMMR (immunohistochemistry) or MSS (PCR or NGS)
4. Have at least one measurable lesion (RECIST v1.1);
5. ECOG PS score is 0 or 1;
6. Expected survival exceeds 3 months;

7. The main organ functions are normal, which meets the following criteria:

   Absolute neutrophil count ≥ 1.5 x 10 ^ 9/L Hemoglobin ≥ 9 g/dL Platelet count ≥ 100 x 10 ^ 9/L Creatinine clearance rate ≥ 50 mL/min, evaluated using the Cockcroft&Gault formula Serum total bilirubin<1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) ≤ 2.5 x ULN (unless liver metastasis leads to abnormal liver function, aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 5 x ULN) All patients have normal coagulation function. For patients receiving anticoagulant therapy (excluding platelet anticoagulants), it should be confirmed that the INR has reached a sufficient therapeutic level.

8. The subjects voluntarily joined this study and signed informed consent forms, demonstrating good compliance and cooperation with follow-up;
9. Women with fertility: must agree to use reliable methods of contraception for at least 180 days from the signing of the informed consent form until the last administration of the study drug. And the serum HCG test must be negative within 7 days before starting the study treatment; And it must be non lactating. If a female patient has already menstruated, has not yet reached postmenopausal status (continuous absence of menstruation for ≥ 12 months, no other reasons found besides menopause), and has not undergone sterilization surgery (such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), it is considered that the patient has fertility;
10. For male patients whose partners are women with fertility, they must agree to use reliable methods of contraception for at least 180 days from the signing of the informed consent form until the last administration of the study drug. Male patients must also agree not to donate sperm during the same time period.

Exclusion Criteria:

1. Previously received TAS-102 treatment.
2. Previously received immunotherapy, including immune checkpoint inhibitors (such as anti-PD-1/L1 antibodies, anti-CTLA-4 antibodies, anti-CD47 antibodies, anti-SIRP α antibodies, anti-LAG-3 antibodies, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immunotherapy, and any other treatment targeting the immune mechanism of tumor.
3. Severe wounds that do not heal, ulcers that do not heal, or fractures that do not heal.
4. Known coagulation disorders and bleeding disorders that increase the risk of bleeding.
5. Researchers believe that patients are unlikely to comply with oral medication treatment plans or study requirements for scheduled evaluations.
6. Pregnant, lactating women or those who may become pregnant during the study period.
7. Symptomatic central nervous system metastasis with unstable nervous system or the need to increase steroid dosage to control central nervous system diseases.
8. Suffering from severe or uncontrolled active acute or chronic infections.
9. Suffering from interstitial lung disease and/or pneumonia, or pulmonary arterial hypertension.

Researchers believe that uncontrolled arterial hypertension or uncontrolled or symptomatic arrhythmia.

11. Study whether there have been deep arterial thromboembolic events, including cerebrovascular accidents or myocardial infarction, within 6 months prior to the start of the first treatment. Study the occurrence of deep vein thromboembolism events within 4 weeks prior to the first treatment.

12. Severe/unstable angina, symptomatic congestive heart failure, New York Heart Association (NYHA) class III or IV.

13. Other malignant tumors, including those that have received curative treatment and have a remission period of less than 5 years during screening. Patients with cervical carcinoma in situ and basal cell carcinoma who can be cured with appropriate treatment are exempt from this minimum required remission period.

Receive systemic immunosuppressive therapy (excluding prophylactic or long-term low-dose steroids [≤ 20 mg/day prednisone equivalent]).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ivonescimab	Drug: Ivonescimab,TAS-102; Ivonescimab,20mg/kg,i.v.,D1,Q3w TAS-102,35mg/m2,bid,D1-5,Q2W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS rate at 18 weeks	The progression free survival rate (PFS) at 18 weeks refers to the proportion of patients who have experienced objective deterioration or progression (including death) of the disease for the first time since the start of treatment, and whose survival time has reached or exceeded 18 weeks	At the end of Cycle 6 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	The ORR is defined as the proportion of patients with a response of CR or PR	At the end of Cycle 6 (each cycle is 28 days)
Overall survival (OS)	From the date of randomization until the date of death	From date of randomization to death from any cause, assessed up to 2 years

Collaborators and Investigators

• Sponsor: Huai'an First People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 13, 2025
• First Submitted That Met QC Criteria: April 13, 2025
• First Posted (Actual): April 20, 2025

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 13, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: intestinal cancer，Ivonescimab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Colonic Diseases; Carcinoma; Colorectal Neoplasms; Adenocarcinoma
• Other Study ID Numbers: HACRC-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No