Clinical trial NCT05827614: Study of the CHK1 Inhibitor BBI-355, an ecDNA-directed Therapy (ecDTx), in Subjects With Tumors With Oncogene Amplifications
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: 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
Keywords: ecDNA
extrachromosomal DNA
Amplification
Oncogene Amplification
Checkpoint kinase 1
CHK1
EGFR amplification
FGFR1 amplification
FGFR2 amplification
FGFR3 amplification
Lead sponsor: Boundless Bio
Sponsor class: INDUSTRY
First posted: 2023-04-25
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: BBI-355 single agent dose escalation and expansion, and BBI-355 dose escalation in combination with select targeted therapies.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)
measure: 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
timeFrame: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, and futibatinib
timeFrame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
measure: Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, and futibatinib
timeFrame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
measure: Time to Cmax (Tmax) of BBI-355, erlotinib, and futibatinib
timeFrame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
measure: Area under the concentration time curve (AUC) of BBI-355, erlotinib, and futibatinib
timeFrame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
measure: Anti-tumor activity of BBI-355 as a single agent and in combination with either erlotinib or futibatinib
timeFrame: 1-2 years: Start of Cycle 1 until documented disease progression or death (each cycle is 28 days)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology
state: California
city: Denver
country: United States
facility: HealthONE
state: Colorado
city: Lake Mary
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Fairway
country: United States
facility: The University of Kansas
state: Kansas
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: NEXT Oncology - Dallas
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Seattle
country: United States
facility: University of Washington, Fred Hutchinson Cancer Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Boundless Bio
name: Robert Doebele, MD, PhD
role: STUDY_DIRECTOR
References:
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.
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.
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.
citation: 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.