JAB-BX102 Monotherapy and Combination With Pembrolizumab in Adult Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is to evaluate the safety and tolerability of JAB-BX102 monotherapy and combination therapy with pembrolizumab in adult participants with advanced solid tumors.

Detailed Description
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The primary objective of this study is to evaluate the safety and tolerability of JAB-BX102 monotherapy to determine the MTD(maximum tolerated dose) and RP2D(Recommended Phase 2 Dose) during Dose Escalation phase; then to evaluate preliminary antitumor activity when JAB-BX102 is administered in combination with pembrolizumab during Dose Expansion phase in patients with advanced solid tumors.

Official Title
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A Phase 1/2a, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-BX102 Monotherapy and Combination With Pembrolizumab in Adult Patients With Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Biological: JAB-BX102 (anti-CD73 monoclonal antibody)
* Biological: pembrolizumab (anti-PD-1 monoclonal antibody)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to provide an archived tumor sample Must have histologically or cytologically confirmed metastatic or locally advanced solid tumor Must be refractory to or become intolerant of existing therapy(ies) known to provide clinical benefit for their condition, or patient has no access to SOC treatment. Must have at least 1 measurable lesion per RECIST v1.1 Must have adequate organ functions Exclusion Criteria: Has central nervous system(CNS) metastases or carcinomatous meningitis, except if CNS metastases treated and no evidence of radiographic progression or hemorrhage for at least 28 days Active infection requiring systemic treatment within 7 days Active hepatitis C virus(HBV), hepatitis C virus(HCV), or HIV Any severe and/or uncontrolled medical conditions Left ventricular ejection fraction(LVEF) ≤50% assessed by echocardiogram (ECHO) or multigated acquisition scan (MUGA) QTcF(Corrected QT interval - Fredericia formula) interval >470 msec Experiencing unresolved CTCAE 5.0 Grade >1 toxicities

Ages Eligible for Study
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Minimum Age: 18 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: Arm A, JAB-BX102 monotherapy, Phase 1, Dose Escalation<br>Dose escalation of JAB-BX102 will be administered as monotherapy to determine the MTD and RP2D. | Biological: JAB-BX102 (anti-CD73 monoclonal antibody)<br>* Administered by intravenous infusion (IV)<br>|
| Experimental: Arm B, JAB-BX102 combination with pembrolizumab, Phase 2a, Dose Expansion<br>JAB-BX102 will be administered in combination with pembrolizumab in specific solid tumor patients to evaluate the preliminary antitumor activity. | Biological: JAB-BX102 (anti-CD73 monoclonal antibody)<br>* Administered by intravenous infusion (IV)<br>Biological: pembrolizumab (anti-PD-1 monoclonal antibody)<br>* Administered by intravenous infusion (IV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation phase Number of participants with dose limiting toxicities (DLTs) | A DLT is defined as the clinically significant TRAE(treatment-related adverse events) or abnormal laboratory values assessment during the first 21 days of Cycle 1 and excludes events that are deemed clearly related to underlying disease, progression, or intercurrent illness. | First 21 days of Cycle 1 | 
| Dose Escalation and Dose Expansion phase: Number of participants with adverse events | Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE 5.0. | Up to 3 years | 
| Dose Expansion phase: Overall response rate (ORR) | ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1. | Up to 3 years - from baseline to RECIST confirmed Progressive Disease | 
| Expansion phase: Duration of response (DOR) | DOR is defined as the time from the participant's initial objective response (CR or PR) to disease progression per CTCAE v1.1 or death due to any cause, whichever occurs first. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize the pharmacokinetics(PK) profile of JAB-BX102 as a single agent and in combination with Pembrolizumab | observed plasma concentration of JAB-BX102 | Up to 3 years | 
| Dose Escalation phase: Overall response rate (ORR) | The percentage of participants with complete response (CR) or partial response (PR) on RECIST v 1.1. | Up to 3 years - from baseline to RECIST confirmed Progressive Disease | 
| Dose Escalation phase: Duration of response (DOR) | DOR is defined as the time from the participant's initial objective response (CR or PR) to disease progression per CTCAE v1.1 or death due to any cause, whichever occurs first. | Up to 3 years | 
| Dose Escalation and Dose Expansion phase: Disease Control Rate (DCR) | DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) per CTCAE v1.1. | Up to 3 years | 
| Dose Escalation and Dose Expansion phase: Progression-free survival (PFS) | PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression per CTCAE v1.1 or death which occurs first | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumor