A Clinical Studyf of SHR-1701 or Placebo in Combination With BP102 and XELOX in the First-line Treatment of mCRC

Study Overview
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Brief Summary
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This is a two-arm, randomized, double-blinded, multicenter phase II/III clinical study to evaluate the safety and clinical efficacy of SHR-1701 or placebo in combination with BP102 (biosimilar to bevacizumab) and XELOX in first-line treatment of patients with mCRC.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II/III Study of SHR-1701 or Placebo in Combination With BP102 (Biosimilar to Bevacizumab) and XELOX in First-line Treatment of mCRC

Conditions
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Metastatic Colorectal Cancer (mCRC)

Intervention / Treatment
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* Drug: SHR-1701、 BP102 、XELOX
* Drug: SHR-1701、 BP102 、XELOX
* Drug: placebo、 BP102、 XELOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with unresectable recurrent or metastatic adenocarcinoma of the colon or rectum confirmed histologically For subjects who have not previously received any systemic antitumor therapy and who have previously received neoadjuvant or adjuvant therapy, the first detection of recurrence or metastasis should be ≥12 months after the last administration of neoadjuvant or adjuvant therapy At least 1 measurable lesion according to RECIST V1.1 The vital organs are functioning well ECOG score is 0   1 Contraception was initiated from the signing of the informed consent until at least 6 months after the last dosing of the study drug Exclusion Criteria: Recurrent or metastatic lesions can be treated with radical surgery Presence of central nervous system or meningeal metastases; Moderate and severe ascites of clinical symptoms;Uncontrolled or moderate or greater pleural effusion or pericardial effusion Poorly controlled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg in the case of regular antihypertensive therapy) and prior hypertensive crisis or hypertensive encephalopathy Severe cardiovascular and cerebrovascular diseases;Have clinical heart symptoms or diseases that are not well controlledSubjects with a history of myocardial infarction or unstable angina pectoris Subject with current interstitial pneumonia or interstitial lung disease, or with a previous history of interstitial pneumonia or interstitial lung disease requiring hormone therapy Previous treatment with targeted T cell costimulatory molecules and immune checkpoint inhibitors;Previous treatment with antiepidermal growth factor receptor or any antiangiogenic drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1701 in combination with BP102 and XELOX（Phase 2）<br> | Drug: SHR-1701、 BP102 、XELOX<br>* Phase 2：Single Group Drug:SHR-1701 30mg/kg，IV ,every 3 week Drug：BP102 7.5mg/kg，IV,every 3 week Drug: Oxaliplatin 130mg/m2 ，IV,every 3 week Drug:Capecitabine The total daily dose was 2000mg/m2, OR，Each cycle was administered for 2 consecutive weeks, followed by a week of rest, with a treatment cycle every 21 days<br>|
| Experimental: SHR-1701 in combination with BP102 and XELOX （Phase 3）<br> | Drug: SHR-1701、 BP102 、XELOX<br>* Phase 3：Randomized Drug:SHR-1701 30mg/kg，IV ,every 3 week Drug：BP102 7.5mg/kg，IV,every 3 week Drug: Oxaliplatin 130mg/m2 ，IV,every 3 week Drug:Capecitabine The total daily dose was 2000mg/m2, OR，Each cycle was administered for 2 consecutive weeks, followed by a week of rest, with a treatment cycle every 21 days<br>|
| Placebo Comparator: placebo in combination with BP102 and XELOX<br> | Drug: placebo、 BP102、 XELOX<br>* Phase 3：Randomized Drug:Placebo 30mg/kg，IV ,every 3 week Drug：BP102 7.5mg/kg，IV,every 3 week Drug: Oxaliplatin 130mg/m2 ，IV,every 3 week Drug:Capecitabine The total daily dose was 2000mg/m2, OR，Each cycle was administered for 2 consecutive weeks, followed by a week of rest, with a treatment cycle every 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2:ORR | Objective response rate (assessed by the investigators based on RECIST v1.1) | up to 2 years | 
| Phase 2:Incidence of Adverse Events (AEs) by CTCAE v5.0 | Assess safety and tolerability of SHR-1701 in combination with BP102 and XELOX | up to 2 years | 
| Phase 3:PFS | Progression-free survival (assessed by independent radiological review committee (IRRC) based on RECIST v1.1) | from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DCR | Disease control rate，the proportion of patients with the best overall response of CR, PR, or stable disease (SD) 。 | up to 2 years | 
| OS | Overall survival ，from the date of first dose unitl the date of death from any cause。 | up to 2 years | 
| PFS | Progression-free survival from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed (assessed by independent radiological review committee (IRRC) based on iRECIST，by the investigators based on RECIST v1.1))。 | up to 2 years | 
| Duration of response | Duration of response，from the date when CR or PR (whichever recorded earlier) is firstly achieved until the date when disease progression or death is firstly recorded (whichever occurs earlier),assessed | up to 2 years |