A Phase 1 Dose Escalation and Expansion Study Of SHR-1916 In Subjects With Locally Advanced Or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This is a first in human, open-label, dose escalation and expansion Phase 1 study of SHR-1916 in adult patients with locally advanced or metastatic solid tumors.

Official Title
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An Open-Label, Multicenter, Dose Escalation And Expansion Study Of SHR-1916 In Subjects With Locally Advanced Or Metastatic Solid Tumor Malignancies

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: SHR-1916


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and the willingness to sign a written informed consent document； Aged between 18-75 years old; Histologically or cytologically confirmed advanced or metastatic malignant tumor; Presence of at least of one measurable lesion in agreement to RECIST criteria; Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1; Life expectancy >12 weeks; Adequate organ performance based on laboratory blood tests; Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Exclusion Criteria: Patients who have received cytokines (IL-2, IFN-α)as anti-tumor therapy within 6 months before the first dose; Previous systemic therapy within 28 days before the first dose; Previous therapeutic surgery within 28 days, and diagnostic surgery within 14 days prior to the first dose; Received live attenuated vaccine within 28 days before the first dose, or expected to receive live attenuated vaccine during the study treatment period; Patients who received systemic immunosuppressive therapy within 14 days before the first dose; Patients with known or suspected brain metastasis； Subjects with interstitial pneumonia or interstitial lung disease, with a history of interstitial pneumonia or interstitial lung disease limiting self care ADL or with life-threatening respiratory compromise, with a history of pulmonary fibrosis, lasting pneumonia, drug- or radiation-induced pneumonia, and congenital pneumonia that may otherwise interfere with the judgement of immune-related pulmonary toxicity, or with any evidence of active pneumonia as shown on chest CT scans; Patients with history of autoimmune diseases; History of immunodeficiency (including HIV infection) or organ transplantation; Known active hepatitis B or C infection; Other serious accompanying illnesses, which, in the researcher's opinion, could seriously adversely affect the safety of the treatment.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1916<br> | Drug: SHR-1916<br>* All participants receive SHR-1906 alone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limited Toxicity (DLT) |  | 21 Days (first cycle) | 
| Maximum tolerable dose (MTD) |  | 21 Days (first cycle) | 
| Recommended dose for phase II (RP2D) |  | Up to 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs （Adverse Events） |  | 30 days after last dose | 
| Area under the plasma concentration time curve in the dosing interval AUC(TAU) of SHR-1916 |  | 30 days after last dose | 
| Maximum observed plasma concentration (Cmax) of SHR-1916 |  | 30 days after last dose | 
| Minimum observed plasma concentration (Cmin) of SHR-1916 |  | 30 days after last dose | 
| Time of maximum observed plasma concentration (Tmax) of SHR-1916 |  | 30 days after last dose | 
| Percentage of NK cell and CD8+ T cell by flow cytometry |  | 30 days after last dose | 
| Absolute count values of NK cell and CD8+ T cell by flow cytometry |  | 30 days after last dose | 
| Peripheral plasma concentration of sCD25 |  | 30 days after last dose | 
| Immunogenicity analysis to assess anti-drug antibodies (ADA) to SHR-1916 in human serum |  | 30 days after last dose | 
| ORR（Objective Response Rate） |  | at the time point of every 9 weeks | 
| DCR（Disease Control Rate） |  | at the time point of every 9 weeks | 
| DoR（Duration of Response） |  | up to 2 years | 
| PFS（Progression-Free-Survival） |  | up to 2 years | 
| 12-month-survival Rate |  | up to 2 years |