Study of the CHK1 Inhibitor BBI-355, an ecDNA-directed Therapy, in Subjects With Tumors With Oncogene Amplifications

Study Overview
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Brief Summary
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BBI-355 is an orally available, potent, and selective checkpoint kinase 1 (or CHK1) small molecule inhibitor in development as an ecDNA (extrachromosomal DNA) directed therapy (ecDTx). This is a first-in-human, open-label, non-randomized, 3-part, Phase 1/2 study to determine the safety profile and identify the maximum tolerated dose and recommended Phase 2 dose of BBI-355 administered as a single agent or in combination with select therapies.

Detailed Description
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BBI-355 will be administered orally every other day to subjects with locally advanced or metastatic non-resectable solid tumors harboring oncogene amplifications, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.

Official Title
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An Open-Label, First-in-Human, Dose-Escalation and Dose-Expansion, Phase 1/2 Study of BBI-355 and BBI-355 in Combination With Select Therapies in Subjects With Locally Advanced or Metastatic Solid Tumors With Oncogene Amplifications

Conditions
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Liposarcoma, Ovarian Cancer, Endometrial Cancer, Non-small Cell Lung Cancer, Non-Small Cell Lung Adenocarcinoma, Non-Small Cell Squamous Lung Cancer, Head and Neck Squamous Cell Carcinoma, Esophageal Cancer, Gastric Cancer, Breast Cancer, Bladder Cancer

Intervention / Treatment
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* Drug: BBI-355


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Locally advanced or metastatic non-resectable solid tumors, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists, Evidence of oncogene amplification, Availability of FFPE tumor tissue, archival or newly obtained, Measurable disease as defined by RECIST Version 1.1, Adequate hematologic function, Adequate hepatic and renal function, Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1, Other inclusion criteria per study protocol. Key Exclusion Criteria: Prior exposure to CHK1 inhibitors, Hematologic malignancies, Primary CNS malignancy, leptomeningeal disease, or symptomatic active CNS metastases, with exceptions per study protocol, Prior or concurrent malignancies, with exceptions per study protocol, History of HBV, HCV or HIV infection, Clinically significant cardiac condition, Active or history of interstitial lung disease (ILD) or pneumonitis, or history of ILD or pneumonitis requiring steroids or other immunosuppressive medications, QTcF > 470 msec, Prior organ allograft transplantations or allogeneic peripheral blood stem cell/bone marrow transplantation, Other exclusion criteria per study protocol.

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
Interventional Model Description: BBI-355 single agent therapy dose escalation and expansion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Agent Therapy Dose Escalation<br>Single agent therapy BBI-355, administered orally every other day in 28-day cycles | Drug: BBI-355<br>* Oral CHK1 inhibitor<br>|
| Experimental: Single Agent Therapy Dose Expansion<br>Single agent therapy BBI-355, administered orally every other day in 28-day cycles | Drug: BBI-355<br>* Oral CHK1 inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-355 | TEAEs will be assessed and severity assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. | Start of Cycle 1 until 30 days following last dose (each cycle is 28 days) | 
| Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of BBI-355 | The MTD and/or RP2D of BBI-355 will be determined. | Start of Cycle 1 until 30 days following last dose (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of BBI-355 | Maximum observed plasma concentration (Cmax) of BBI-355 will be determined. | Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) | 
| Trough observed plasma concentration (Ctrough) of BBI-355 | Trough observed plasma concentration (Ctrough) of BBI-355 will be determined. | Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) | 
| Time to Cmax (Tmax) of BBI-355 | Time to Cmax (Tmax) of BBI-355 will be determined. | Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) | 
| Area under the concentration time curve (AUC) of BBI-355 | Area under the concentration time curve (AUC) of BBI-355 will be determined. | Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) | 
| Anti-tumor activity of BBI-355 | Tumor response will be determined by RECISTv1.1. | 1-2 years: Start of Cycle 1 until documented disease progression or death (each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ecDNA, extrachromosomal DNA, Amplification, Oncogene Amplification, Checkpoint kinase 1, CHK1