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

Breast Cancer Clinical Trial

— POTENTIATE  

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05827614
• Other study ID #: BBI-355-101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 24, 2023
• Est. completion date: September 30, 2027

Study information

• Verified date: February 2024
• Source: Boundless Bio
• Contact: Sara Weymer
• Phone: 16198211090
• Email: ClinicalDevelopment[@]boundlessbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: September 30, 2027
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

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.

Related Conditions & MeSH terms

• Adenocarcinoma of Lung
• Bladder Cancer
• Breast Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Esophageal Cancer
• Gastric Cancer
• Head and Neck Squamous Cell Carcinoma
• Liposarcoma
• Lung Neoplasms
• Non-small Cell Lung Cancer
• Ovarian Cancer
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• BBI-355
Oral CHK1 inhibitor
• Erlotinib
EGFR Inhibitor
• Futibatinib
FGFR1-4 Inhibitor

Locations

Country	Name	City	State
United States	NEXT Oncology	Fairfax	Virginia
United States	START Midwest	Grand Rapids	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NEXT Oncology	San Antonio	Texas
United States	Sarcoma Oncology	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Boundless Bio

Country where clinical trial is conducted

United States, 

References & Publications (4)

Kim H, Nguyen NP, Turner K, Wu S, Gujar AD, Luebeck J, Liu J, Deshpande V, Rajkumar U, Namburi S, Amin SB, Yi E, Menghi F, Schulte JH, Henssen AG, Chang HY, Beck CR, Mischel PS, Bafna V, Verhaak RGW. Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nat Genet. 2020 Sep;52(9):891-897. doi: 10.1038/s41588-020-0678-2. Epub 2020 Aug 17. — View Citation

Lange JT, Rose JC, Chen CY, Pichugin Y, Xie L, Tang J, Hung KL, Yost KE, Shi Q, Erb ML, Rajkumar U, Wu S, Taschner-Mandl S, Bernkopf M, Swanton C, Liu Z, Huang W, Chang HY, Bafna V, Henssen AG, Werner B, Mischel PS. The evolutionary dynamics of extrachromosomal DNA in human cancers. Nat Genet. 2022 Oct;54(10):1527-1533. doi: 10.1038/s41588-022-01177-x. Epub 2022 Sep 19. — View Citation

Turner KM, Deshpande V, Beyter D, Koga T, Rusert J, Lee C, Li B, Arden K, Ren B, Nathanson DA, Kornblum HI, Taylor MD, Kaushal S, Cavenee WK, Wechsler-Reya R, Furnari FB, Vandenberg SR, Rao PN, Wahl GM, Bafna V, Mischel PS. Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature. 2017 Mar 2;543(7643):122-125. doi: 10.1038/nature21356. Epub 2017 Feb 8. — View Citation

Wu S, Bafna V, Chang HY, Mischel PS. Extrachromosomal DNA: An Emerging Hallmark in Human Cancer. Annu Rev Pathol. 2022 Jan 24;17:367-386. doi: 10.1146/annurev-pathmechdis-051821-114223. Epub 2021 Nov 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-355 as a single agent and in combination with each of the following agents: erlotinib or futibatinib	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)
Primary	Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of BBI-355 as a single agent and in combination with either erlotinib or futibatinib	The MTD and/or RP2D of BBI-355 as a single agent and in combination with either erlotinib or futibatinib, will be determined.	Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)
Secondary	Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, and futibatinib	Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, and futibatinib will be determined.	Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Secondary	Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, and futibatinib	Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, and futibatinib will be determined.	Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Secondary	Time to Cmax (Tmax) of BBI-355, erlotinib, and futibatinib	Time to Cmax (Tmax) of BBI-355, erlotinib, and futibatinib will be determined.	Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Secondary	Area under the concentration time curve (AUC) of BBI-355, erlotinib, and futibatinib	Area under the concentration time curve (AUC) of BBI-355, erlotinib, and futibatinib will be determined.	Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Secondary	Anti-tumor activity of BBI-355 as a single agent and in combination with either erlotinib or futibatinib	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)