A Trial of SHR-2002 Injection or Combined With Other Anti-cancer Medication in Advanced Malignant Tumors of Patients

Study Overview
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Brief Summary
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The study is being conducted to evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of SHR-2002 injection monotherapy and in combination with other anti-cancer therapy for advanced malignant tumors of patients. To explore the reasonable dosage of SHR-2002 injection monotherapy and dosage regimen of combination therapy for advanced malignant tumors of patients.

Official Title
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A Phase I Clinical Study on the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of SHR-2002 Injection or in Combination With Other Anti-cancer Therapy in Advanced Malignant Tumors of Patients

Conditions
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Advanced Malignant Tumors

Intervention / Treatment
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* Drug: SHR-2002 injection、Camrelizumab for Injection, SHR-1316 injection, SHR-1701 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and voluntarily agrees to participate by giving written informed consent for the study; Male or female aged ≥18 years and ≤70 years at the time of signing the ICF; Histopathologically or cytologically documented advanced or metastatic malignancies; An Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; Life expectancy ≥12 weeks; Adequate organ functions as defined; Female and male patients of reproductive potential must agree to use highly effective contraception during the study treatment period and within 6 months after the last investigational drug administration; Female of childbearing potential must have a negative serum human chorionic gonadotropin (HCG) test within 7 days before the first dose of the investigational drugs and must not be breastfeeding. Exclusion Criteria: Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis; Patients with active brain metastasis (without medical control or with clinical symptoms), cancerous meningitis, spinal cord compression, or patients with a history of primary tumors of the central nervous system ; Patients with tumor-related pain that cannot be controlled as determined by the investigator; Uncontrollable third-space effusion, such as pleural effusion, pericardial effusion or peritoneal effusion; Systemic anti-tumor therapy within 28 days prior to the first dose of the study treatment; Surgical procedures requiring general anesthesia within 28 days prior to the first dose of the study treatment; Patients who have received >30 Gy of radical radiotherapy within 28 days before the first dose of study treatment; Unresolved CTCAE Grade >1 toxicity attributed to any prior anti-tumor therapy; Use of live attenuated vaccines within 28 days before the first dose of the study treatment; Patients who have received any systemic immunosuppressants within 14 days prior to the first dose of study treatment; Patients with interstitial pneumonitis or interstitial lung disease; past history of interstitial pneumonitis or interstitial lung disease requiring hormone therapy; History of autoimmune diseases; History of clinically significant bleeding symptom or bleeding tendency within 3 months before the first dose of study treatment; History of clinically significant cardiovascular or cerebrovascular diseases within 6 months prior to the first dose of study treatment; Evidence or history of arterial/venous thrombosis within 3 months before the first dose; Prior malignancy (other than current malignant tumor) within 5 ears before the first dose of study treatment; Known history of serious allergic reactions to the investigational product or its main ingredients; History of immunodeficiency; Presence of active hepatitis B or active hepatitis C; Severe infections within 4 weeks prior to the first study treatment; Evidence or history of active pulmonary tuberculosis within 1 year before study entry; any other conditions that are not suitable for participation in the study in the investigator's opinion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Interventional Model Description: SHR-2002 injection monotherapy and in combination with other anti-cancer therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Group<br> | Drug: SHR-2002 injection、Camrelizumab for Injection, SHR-1316 injection, SHR-1701 injection<br>* Firstly Dose Escalation and Dose Expansion of SHR-2002 injection monotherapy should be conducted. After RP2D and MTD of the SHR-2002 injection monotherapy were confirmed, Dose Escalation, Dose Expansion and Efficacy Expansion of SHR-2002 injection in combination with other anti-cancer treatment would be completed, including Camrelizumab for Injection, or SHR-1316 injection, or SHR-1701 injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose | The Maximum tolerated dose of SHR-2002 injection monotherapy or in combination with Camrelizumab for Injection, or SHR-1316 injection, or SHR-1701 injection | first dose of study medication up to 21 days | 
| Recommended phase II dose | The Recommended phase II dose of SHR-2002 injection monotherapy or in combination with Camrelizumab for Injection, or SHR-1316 injection, or SHR-1701 injection | first dose of study medication up to 21 days | 
| Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) | Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | from signature completion of ICF to 90 days after the last dose or to the beginning of the new anti-cancer therapy, whichever came first, assessed up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | PK parameters of single dose of SHR-2002 injection monotherapy | 0.5 hour before first dose to the 336 hours after first dose | 
| Cmax | PK parameters of single dose of SHR-2002 injection monotherapy | 0.5 hour before first dose to the 336 hours after first dose | 
| AUC0-t | PK parameters of single dose of SHR-2002 injection monotherapy | 0.5 hour before first dose to the 336 hours after first dose | 
| AUC0-∞ | PK parameters of single dose of SHR-2002 injection monotherapy | 0.5 hour before first dose to the 336 hours after first dose | 
| t1/2 | PK parameters of single dose of SHR-2002 injection monotherapy | 0.5 hour before first dose to the 336 hours after first dose | 
| CL | PK parameters of single dose of SHR-2002 injection monotherapy | 0.5 hour before first dose to the 336 hours after first dose | 
| Vss | PK parameters of single dose of SHR-2002 injection monotherapy | 0.5 hour before first dose to the 336 hours after first dose | 
| Cmax, ss | PK parameters of multiple doses of SHR-2002 monotherapy | 0.5 hour before second dose to the 30 days after last dose | 
| Ctrough, ss | PK parameters of multiple doses of SHR-2002 monotherapy | 0.5 hour before second dose to the 30 days after last dose | 
| Rac | PK parameters of multiple doses of SHR-2002 monotherapy | 0.5 hour before second dose to the 30 days after last dose | 
| RO | Receptor occupancy, PD indicators of SHR-2002 injection monotherapy | 0.5 hour before second dose to the 30 days after last dose | 
| Cytokine concentration | PD indicators of SHR-2002 injection monotherapy | 0.5 hour before second dose to the 30 days after last dose | 
| Ctrough, ss | PK parameters of SHR -2002, Camrelizumab for Injection, SHR-1316 injection and SHR-1701 injection during combination therapy period | 0.5 hour before second dose to the 90 days after last dose | 
| Rac | PK parameters of SHR -2002, Camrelizumab for Injection, SHR-1316 injection and SHR-1701 injection during combination therapy period | 0.5 hour before second dose to the 90 days after last dose | 
| ADA | Anti-drug antibody, Immunogenicity of SHR-2002 in monotherapy and combination therapy, Camrelizumab for Injection, SHR-1316 injection and SHR-1701 injection | 0.5 hour before second dose to the 90 days after last dose | 
| NAb | Immunogenicity of Camrelizumab for Injection, SHR-1316 injection and SHR-1701 injection | 0.5 hour before second dose to the 90 days after last dose | 
| ORR | Objective Response Rate, Efficacy endpoints of SHR-2002 injection monotherapy or in combination with Camrelizumab for Injection, or SHR-1316 injection, or SHR-1701 injection in treatment of patients with Advanced Malignant Tumors | from the date of the first dose to the date of disease progression evaluated based on RECIST v1.1 criteria, death, lost to follow-up, voluntary withdrawal, or initiation of other anti-tumor treatment, whichever occurs first, assessed up to 6 months] | 
| DoR | Duration of response, Efficacy endpoints of SHR-2002 injection monotherapy or in combination with Camrelizumab for Injection, or SHR-1316 injection, or SHR-1701 injection in treatment of patients with Advanced Malignant Tumors | from the date of the firstly documented tumor response to the date of the firstly documented disease progression or the date of death for any reason, assessed up to 6 months | 
| DCR | Disease control rate, Efficacy endpoints of SHR-2002 injection monotherapy or in combination with Camrelizumab for Injection, or SHR-1316 injection, or SHR-1701 injection in treatment of patients with Advanced Malignant Tumors | from the date of the first dose to the date of the firstly documented disease progression (evaluated based on RECIST v1.1 criteria) or the date of death for any reason, assessed up to 6 months | 
| PFS | Progression-free survival, Efficacy endpoints of SHR-2002 injection monotherapy or in combination with Camrelizumab for Injection, or SHR-1316 injection, or SHR-1701 injection in treatment of patients with Advanced Malignant Tumors | from the date of the first dose to the date of the firstly documented disease progression (evaluated based on RECIST v1.1 criteria) or the date of death for any reason, assessed up to 6 months | 
| OS | Overall survival, Efficacy endpoints of SHR-2002 injection monotherapy or in combination with Camrelizumab for Injection, or SHR-1316 injection, or SHR-1701 injection in treatment of patients with Advanced Malignant Tumors | from the date of the first dose to the date of death for any reason，assessed up to 100 months |