A Study of Ametumumab in Combination With Anti-PD-1 Monoclonal Antibody and FOLFIRI in Patients With RAS Wild-type Advanced Colorectal Cancer

Study Overview
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Brief Summary
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This is a multicenter, open-label, parallel-group, randomised, A phase IIb clinical trial of efficacy and safety of Ametumumab in combination with anti-PD-1 monoclonal antibody and FOLFIRI versus Ametumumab or Cetuximab in combination with FOLFIRI in patients with RAS wild-type advanced colorectal cancer.

Detailed Description
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This is a multicenter, open-label, parallel-group, randomised, phase IIb trial. This study is to evaluate and compare the efficacy and safety of Ametumumab (anti-EGFR monoclonal antibody) combined with anti-PD-1 monoclonal antibody in first-line treatment of RAS wild-type colorectal cancer patients, as well as to assess the immunogenicity and pharmacokinetic profile and recommend dosing regimen for phase III clinical trials.Conditions and keywords.

Official Title
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A Multicenter, Open-label, Parallel-group，Randomised, Phase IIb Trial of Efficacy and Safety of Ametumumab in Combination With Anti-PD-1 Monoclonal Antibody and FOLFIRI Versus Ametumumab or Cetuximab in Combination With FOLFIRI in Patients With RAS Wild-type Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Ametumumab
* Drug: Anti-PD-1 monoclonal antibody
* Drug: Cetuximab
* Drug: FOLFIRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily sign written informed consent; Age 18   85 years (inclusive), male or female; •Patients requiring first-line treatment for locally advanced colorectal cancer with distant metastasis or unresectable disease; Histologically or cytologically confirmed adenocarcinoma of the colon or rectum; RAS (KRAS, NRAS) gene is wild-type and no BRAF V600E mutation has been identified; Presence of at least one measurable lesion (non-radiation field) confirmed by CT or MRI that meets RECIST 1.1 criteria; Performance status (ECOG) score 0 or 1. Exclusion Criteria: Previous chemotherapy for colorectal cancerPrevious treatment with anti-EGFR monoclonal antibodies Received systemic anti-tumor treatment approved or of other clinical studies within 4 weeks prior to the first dose. Radiotherapy or surgery within 4 weeks prior to enrollment, except for diagnostic biopsy Participation in other clinical trials within 4 weeks prior to enrollment; Severe skin disease requiring systemic treatment. Presence of serious clinical infection.\ Uncontrolled pleural effusion, pericardial effusion or peritoneal effusion after treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ametumumab (QW) + anti-PD-1 monoclonal antibody+ FOLFIRI<br>Ametumumab 450 mg/m2 (QW) + anti-PD-1 monoclonal antibody (in the case of toripalimab 3 mg/kg, Q2W) + FOLFIRI; | Drug: Ametumumab<br>* A recombinant fully human anti-EGFR monoclonal antibody<br>Drug: Anti-PD-1 monoclonal antibody<br>* Toripalimab 3 mg/kg，Intravenous titration，Q2W<br>Drug: FOLFIRI<br>* Rinotecan hydrochloride，180mg/m2，intravenous titration，Q2W； 5 -Fluorouracil，400 mg/ m2, intravenous push, then 1200 mg/ m2 /day x 2 days, intravenous titration,Q2W; Calcium folinate,400mg/m2,intravenous titration，Q2W<br>|
| Active Comparator: Ametumumab(Q2W) + anti-PD-1 monoclonal antibody + FOLFIRI;<br>Ametumumab 450 mg/m2 (Q2W) + anti-PD-1 monoclonal antibody (in the case of toripalimab 3 mg/kg, Q2W) + FOLFIRI; | Drug: Ametumumab<br>* A recombinant fully human anti-EGFR monoclonal antibody<br>Drug: Anti-PD-1 monoclonal antibody<br>* Toripalimab 3 mg/kg，Intravenous titration，Q2W<br>Drug: FOLFIRI<br>* Rinotecan hydrochloride，180mg/m2，intravenous titration，Q2W； 5 -Fluorouracil，400 mg/ m2, intravenous push, then 1200 mg/ m2 /day x 2 days, intravenous titration,Q2W; Calcium folinate,400mg/m2,intravenous titration，Q2W<br>|
| Active Comparator: Ametumumab (Q2W) + FOLFIRI;<br>Ametumumab 450 mg/m2 (Q2W) + FOLFIRI | Drug: Ametumumab<br>* A recombinant fully human anti-EGFR monoclonal antibody<br>Drug: FOLFIRI<br>* Rinotecan hydrochloride，180mg/m2，intravenous titration，Q2W； 5 -Fluorouracil，400 mg/ m2, intravenous push, then 1200 mg/ m2 /day x 2 days, intravenous titration,Q2W; Calcium folinate,400mg/m2,intravenous titration，Q2W<br>|
| Active Comparator: Cetuximab + FOLFIRI;<br>Cetuximab 500 mg/m2 (Q2W) + FOLFIRI | Drug: Cetuximab<br>* Cetuximab 500 mg/m2 ，Intravenous titration，Q2W<br>Drug: FOLFIRI<br>* Rinotecan hydrochloride，180mg/m2，intravenous titration，Q2W； 5 -Fluorouracil，400 mg/ m2, intravenous push, then 1200 mg/ m2 /day x 2 days, intravenous titration,Q2W; Calcium folinate,400mg/m2,intravenous titration，Q2W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | PFS will be measured from the date of first dose of study drug until first documented clinical or radiographic evidence of disease progression by RECIST 1.1, clinical progression, start of new therapy or death. approximately 45 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | ORR is defined as a CR or PR per RECIST version 1.1 recorded from the date of randomization until date of first documentation of PD, death, or start of new anti-cancer therapy, approximately 45 months. | 
| incidence of adverse events |  | Incidence and severity of AEs graded according to the NCI CTCAE v5.0, Duration of study, approximately 45 months |