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

Sponsor

Boundless Bio (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05827614

Collaborator

(none)

Enrollment

Locations

Arms

33.3

Anticipated Duration (Months)

15.7

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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 Ovarian Cancer Endometrial Cancer Liposarcoma	Drug: BBI-355	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

47 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

BBI-355 single agent therapy dose escalation and expansionBBI-355 single agent therapy dose escalation and expansion

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Apr 24, 2023

Anticipated Primary Completion Date :

Jan 31, 2025

Anticipated Study Completion Date :

Jan 31, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Single Agent Therapy Dose Escalation

Single agent therapy BBI-355, administered orally every other day in 28-day cycles

Drug: BBI-355

Oral CHK1 inhibitor

Experimental: Single Agent Therapy Dose Expansion

Single agent therapy BBI-355, administered orally every other day in 28-day cycles

Drug: BBI-355

Oral CHK1 inhibitor

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.