A Study of ILB2109 in Patients With Advanced Solid Malignancies

Study Overview
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Brief Summary
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This is a multicenter, open-label, phase Ia study to evaluate the safety, tolerability and preliminary efficacy of ILB2109, a A2a receptor antagonist, in patients with locally advanced or metastatic solid malignancies.

Detailed Description
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This is a two-part study consists of dose escalation and dose expansion. The dose escalation part adopts a 3+3 protocol design and consists of 5 cohorts. Based on the data obtained from the escalation study, selected cohorts will be expanded to further investigate the safety and efficacy of the study drug. The escalation part consists of a single-dose cycle (Cycle 0) followed by multiple-dose cycles (Cycle 1 and above). Subjects will be assessed for safety and efficacy outcomes at pre-specified time points.

Official Title
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A Phase Ia, Multicenter, Open-label Study of ILB2109 in Patients With Advanced Solid Malignancies

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: ILB2109


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytological confirmed, solid, malignant tumor that is refractory to standard therapy or for which no standard of care regimen currently exists; At least one assessable tumor lesion according to RECIST v1.1 in dose escalation part of the study ; At least one measurable tumor lesion according to RECIST v1.1 in dose expansion part of the study; Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; Major organ functions are normal, meets pre-specified lab requirements; Females of reproductive age must have a negative serological hCG test during the screening period; Subjects of reproductive age (both male and female) must agree to use contraceptive methods from signing Informed Consent to 90 days post the last dose; Exclusion Criteria: Has received any investigational medicinal product or other systemic anticancer treatment within 4 weeks prior to the first dose of study treatment; Unable to take medication orally, or has impaired GI function; Has received systemic glucocorticoids (prednisone>10 mg/ day or an equivalent dose of another drug of the same class) or other immunosuppressants within 14 days prior to the first dose of study treatment; Has received live, attenuated vaccines within 4 weeks prior to the first dose of study treatment; Has active infection that requires intravenous anti-infective therapy; History of HIV infection, or other acquired, congenital immunodeficiency disease, or a history of organ transplantation; History of serious cardiovascular and cerebrovascular diseases; History of adverse effect from previous antineoplastic therapy that has not returned to CTCAE grade 5.0 ≤1; Cerebral parenchymal or meningeal metastasis; History of ≥ Grade 3 irAE or ≥ Grade 2 myocarditis from previous immune therapy;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment Arm<br> | Drug: ILB2109<br>* ILB2109 tablets by mouth once per day at dosages prespecified by the protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of DLTs | The incidence rate of Dose Limiting Toxicities (DLTs) | At the end of Cycle 0 and 1 (Cycle 0 is 3 days, Cycle 1 is 21 days) | 
| MTD | Determining the maximum tolerated dose (MTD) for subsequent studies | 21 Months | 
| RD | Determining the Recommended Dose (RD) for subsequent studies | 21 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Outcomes | Determining the incidence rate, type and severity of Treatment Emergent Adverse Event (TEAE), Treatment Emergent Serious Adverse Event (TESAE), and lab abnormalities (hematology and major organ function lab tests) based on NCI-CTCAE 5.0; | From Informed Consent to 28 days after the last dose, expected follow-up period 6 months | 
| Objective Response Rate (ORR) |  | Tumor assessment every 6 weeks (+/- 7 days) until disease progression, expected follow-up period 6 months | 
| Progression Free Survival (PFS) |  | Tumor assessment every 6 weeks (+/- 7 days) until disease progression, expected follow-up period 6 months | 
| Overall Survival (OS) |  | Tumor assessment every 6 weeks (+/- 7 days) until disease progression, expected follow-up period 6 months | 
| 1-Year OS |  | Tumor assessment every 6 weeks (+/- 7 days) until disease progression, expected follow-up period 6 months | 
| Time To Response (TTR) | Time from the start of treatment to the first objective tumor response | Tumor assessment every 6 weeks (+/- 7 days) until disease progression, expected follow-up period 6 months | 
| Duration Of Response (DOR) | The time from response to progression/death | Tumor assessment every 6 weeks (+/- 7 days) until disease progression, expected follow-up period 6 months | 
| Clinical Benefit Response (CBR) | The total percentage of patients who achieved a complete response, partial response, or had stable disease for 6 months or more. | Tumor assessment every 6 weeks (+/- 7 days) until disease progression, expected follow-up period 6 months | 
| Maximum Plasma Concentration (Cmax) | Characterize the single-dose and multiple-dose plasma concentration of ILB2109 | Blood samples will be collected at pre-specified time points in Cycles 0, 1 and 2 (Cycle 0 is 3 days, Cycles 1&2 each is 21 days) | 
| Area Under the plasma drug concentration-time Curve (AUC) | Characterize the single-dose and multiple-dose plasma concentration of ILB2109 | Blood samples will be collected at pre-specified time points in Cycles 0, 1 and 2 (Cycle 0 is 3 days, Cycles 1&2 each is 21 days) |