Study of the CHK1 Inhibitor BBI-355, an EcDNA-directed Therapy (ecDTx), in Subjects with Tumors with Oncogene Amplifications (POTENTIATE)

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Status and phase: Enrolling; Phase 1

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

Treatments: Drug: BBI-355; Drug: Futibatinib; Drug: Erlotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05827614

BBI-355-101

Details and patient eligibility

About

BBI-355 is an oral, potent, 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, 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.

Full description

BBI-355 is administered orally in various dosing schedules 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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,
• Single agent arm: Evidence of oncogene amplification,
• BBI-355 combination with erlotinib arm: Evidence of amplification of wildtype EGFR,
• BBI-355 combination with futibatinib arm: Evidence of amplification of wildtype FGFR1, FGFR2, FGFR3, or FGFR4,
• 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:

• Well-known tumor activating oncogene mutations or fusions,
• Prior exposure to CHK1 inhibitors,
• BBI-355 combination with erlotinib arm: Prior exposure to EGFR inhibitors,
• BBI-355 combination with futibatinib arm: Prior exposure to FGFR 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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150 participants in 4 patient groups

Single Agent Dose Escalation

Experimental group

Description:

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

Treatment:

Drug: BBI-355

Single Agent Dose Expansion

Experimental group

Description:

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

Treatment:

Drug: BBI-355

Dose Escalation in Combination with EGFR Inhibitor

Experimental group

Description:

Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.

Treatment:

Drug: Erlotinib

Drug: BBI-355

Dose Escalation in Combination with FGFR Inhibitor

Experimental group

Description:

Combination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles.

Treatment:

Drug: Futibatinib

Drug: BBI-355