IBI397 or Combination Therapies in Patients With Advanced Malignancies

Study Overview
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Brief Summary
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The primary objective of this phase Ia/Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of IBI397 or its Combination Therapies in Patients with Advanced Malignancies

Official Title
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A Phase Ia/Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of IBI397 or Combination Therapies in Patients With Advanced Malignancies

Conditions
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Advanced Malignancies

Intervention / Treatment
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* Drug: IBI397
* Drug: IBI397+Sintilimab
* Drug: IBI397+Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Have failed the standard treatment for locally advanced, recurrent or metastatic solid tumor or have failed at least the second line standard treatment (including autologous stem cell transplantation) or have failed the first line standard treatment and are not eligible for autologous stem cell transplantation Willing to and able to provide written informed consent for the trial and able to comply with protocol-specified visits and related procedures ≥ 18 and ≤ 75 years of age on the day of signing the informed consent Have a performance scale of 0 or 1 on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) Subjects with solid tumor: Have at least one measurable or assessable lesion as defined by RECIST v1.1; Subjects with lymphoma: Have at least one measurable or assessable lesion as defined by Lugano2014 criteria Exclusion Criteria: Has been previously exposed to any CD47 antibody, SIRPα antibody, or CD47/SIRPα recombinant protein or other inhibitors that target the same pathway Is currently participating in another interventional study, except for observational (non-interventional) study or in the survival follow-up phase of an interventional study Requires long-term systemic hormone or any other immunosuppressive drug therapy, excluding inhaled hormone therapy Has acute or chronic active hepatitis B (defined as hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody positive [HBcAb] and hepatitis B virus [HBV] DNA copy number ≥ 1 × 104 copies/ml or ≥ 2000 IU/ml or higher than the lower limit of detection) or acute or chronic active hepatitis C virus (HCV) antibody positive; HCV antibody positive but RNA negative subjects are allowed Has a known history of severe allergic reaction to other monoclonal antibodies, or is allergic to any component of the IBI397 formulation. Is pregnant or breastfeeding

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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI397 single-agent dose escalation<br> | Drug: IBI397<br>* IBI397 single-agent dose escalation： Subjects will receive IBI397 until disease progression, unacceptable toxicity, withdrawal of consent, occurrence of other conditions that require discontinuation of study treatment, or the treatment duration has reached 24 months, whichever occurs first<br>|
| Experimental: IBI397+ Rituximab<br> | Drug: IBI397<br>* IBI397 single-agent dose escalation： Subjects will receive IBI397 until disease progression, unacceptable toxicity, withdrawal of consent, occurrence of other conditions that require discontinuation of study treatment, or the treatment duration has reached 24 months, whichever occurs first<br>Drug: IBI397+Rituximab<br>* IBI397 in combination with rituximab： Subjects will receive IBI397 combination therapy with rituximab until disease progression, unacceptable toxicity, withdrawal of consent, occurrence of other conditions that require discontinuation of study treatment, or the treatment duration has reached 24 months, whichever occurs first<br>|
| Experimental: IBI397 + Sintilimab<br> | Drug: IBI397<br>* IBI397 single-agent dose escalation： Subjects will receive IBI397 until disease progression, unacceptable toxicity, withdrawal of consent, occurrence of other conditions that require discontinuation of study treatment, or the treatment duration has reached 24 months, whichever occurs first<br>Drug: IBI397+Sintilimab<br>* IBI397 in combination with sintilimab： Subjects will receive IBI397 combination therapy with sintilimab until disease progression, unacceptable toxicity, withdrawal of consent, occurrence of other conditions that require discontinuation of study treatment, or the treatment duration has reached 24 months, whichever occurs first<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with treatment related AEs | Number of patients who experienced a treatment related AEs from the frist dose until 90 days after the last dose | Up to 90 days post last dose | 
| Percentage of Subjects with Dose-Limiting Toxicities (DLTs) | To evaluate the safety and tolerability of IBI397 alone or in combination with Sintilimab | Up to 28 Days following first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| area under the plasma concentration-time curve (AUC) |  | Up to 90 days post last dose | 
| maximum concentration (Cmax) |  | Up to 90 days post last dose | 
| clearance (CL) |  | Up to 90 days post last dose | 
| volume of distribution (V) |  | Up to 90 days post last dose | 
| half-life (t1/2) |  | Up to 90 days post last dose | 
| anti-drug antibody (ADA) | Number of Anti-Drug Antibodies (ADA) positive subjects will be counted and percentage of ADA positive subjects will be calculated to evaluate immunogenicity of IBI397 | Up to 90 days post last dose | 
| Objective response rate (ORR) | Objective Response Rate (ORR) is the percentage of Complete Response (CR) plus partial response (PR) assessed per RECIST v1.1 criteria for solid tumors or per Lugano2014 criteria for lymphomas | Up to 2 years after enrollment |