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

Description
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.

Objective
Primary:
-To assess the safety, tolerability, and DLTs of BBI-355 as a single agent administered orally at escalating dose levels in adult subjects with locally advanced or metastatic solid tumors with oncogene amplifications.
-To assess the safety, tolerability, and DLTs of BBI-355 in combination with each of the following agents: erlotinib, futibatinib, or abemaciclib, at escalating dose levels in adults with locally advanced or metastatic solid tumors with corresponding oncogene amplifications.
-To determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of BBI-355 as a single agent.
-To determine the MTD and the RP2D of BBI-355 in combination with each of the following agents: erlotinib, futibatinib, or abemaciclib.

Treatment 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.

Key Eligibility 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.

Applicable Disease Sites
Anal; Any Site; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital