A Phase 1 Study of BB3008 in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1 dose escalation study to evaluate the safety, tolerability, pharmacokinetics, efficacy and preliminary food effect of BB3008 as monotherapy in subjects with advanced solid tumors.

Detailed Description
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This first-in-human (FIH) study of BB3008 will evaluate safety, tolerability, pharmacokinetics (PK) efficacy and preliminary food effect of BB3008 in subjects with advanced solid tumors. The primary objective is to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of BB3008 as monotherapy, and to evaluate the safety and tolerability of BB3008. The secondary objectives include the assessments of PK profile, preliminary efficacy, preliminary food effect (FE) and preliminary metabolites identification of BB3008. The exploratory objectives are to explore biomarkers and C-QTcF analysis.

Official Title
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A Phase I, Open-label, Multicenter Study to Assess Safety, Tolerability, Pharmacokinetic, Efficacy and Preliminary Food Effect of BB3008 Tablet Administered Orally to Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: BB3008 tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fully informed of the study and voluntarily signed the informed consent form (ICF), and willing to follow and have the ability to complete all trial procedures. Subjects with histologically or cytologically confirmed advanced solid tumors who are lacking standard therapy, progressing after adequate standard therapy, or intolerant of standard therapy. ECOG score ≤1. At least one evaluable or measurable lesion as defined by RECIST v1.1. Expected survival ≥ 3 months. adequate organ function. Female subjects of childbearing potential must have a negative pregnancy test prior to the first dose and are required to use effective contraception from signing the ICF until 6 months after the last dose of study treatment. Exclusion Criteria: History of dual-source cancer within 5 years. Presence of known active central nervous system (CNS) and/or leptomeningeal metastases. History of clinically serious cardiovascular and cerebrovascular disease within 6 months. Active infection (including, but not limited to HBV or HCV). Received radical radiotherapy within 12 weeks. Received live virus vaccination within 4 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BB3008 monotherapy<br>The study is composed of fasted dose cohorts and fed dose cohort. BB3008 will be administered orally daily alone as monotherapy in all cohorts. In the fasted dose cohorts, the subjects will receive once daily of BB3008 monotherapy fasted across approximately 6 ascending dose levels. The starting dose is 80 mg/day. In the fed dose cohort, the subjects will receive once daily of BB3008 monotherapy in a fed condition. The dose selected for fed dose cohort must be deemed safe as assessed by safety monitoring committee (SMC). | Drug: BB3008 tablet<br>* BB3008 tablets will be administered orally once daily (QD).<br>* Other names: BB3008;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with dose limiting toxicities (DLTs) | To assess the safety and tolerability of BB3008 tablet as monotherapy in subjects with advanced solid tumors and to determine the maximum tolerated dose (MTD) of BB3008 tablet, and to provide a basis for determination of the recommended dose (RP2D) for Phase II clinical trials. | Single dose to the end of Cycle 1 (each cycle is 21 days) | 
| Number of subjects with adverse events (AEs) and serious adverse events (SAEs) | AEs and SAEs will be characterized by type, seriousness, relationship to study treatment, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0) and timing. | From screening (Day -28 to Day -1) through up to 12 months or until disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Assessments: Peak Plasma Concentration (Cmax) | Blood samples will be collected for PK analyses | Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days) | 
| Pharmacokinetic Assessments: Time to Peak Concentration (Tmax) | Blood samples will be collected for PK analyses | Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days) | 
| Pharmacokinetic Assessments: Area under the plasma concentration-time curve (AUC) | Blood samples will be collected for PK analyses | Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days) | 
| Pharmacokinetic Assessments: Elimination half-life (t½) | Blood samples will be collected for PK analyses | Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days) | 
| Objective response rate (ORR) | Tumor response measured by radiologic imaging techniques at baseline and throughout the study. | From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Duration of response (DOR) | Tumor response measured by radiologic imaging techniques at baseline and throughout the study. | From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Disease control rate (DCR) | Tumor response measured by radiologic imaging techniques at baseline and throughout the study. | From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Progression-free survival (PFS) | Tumor response measured by radiologic imaging techniques at baseline and throughout the study. | From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BB3008, HPK1, First-in-Human, Dose Escalation