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

• ClinicalTrials.gov Identifier: NCT05827614
• Recruitment Status: Recruiting
• First Posted: April 25, 2023
• Last Update Posted: February 28, 2024
• Sponsor: Boundless Bio
• Information provided by (Responsible Party): Boundless Bio

Tracking Information

• First Submitted Date: March 27, 2023
• First Posted Date: April 25, 2023
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: March 24, 2023
• Estimated Primary Completion Date: September 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 27, 2024)

• 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 [ Time Frame: 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 as a single agent and in combination with either erlotinib or futibatinib [ Time Frame: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days) ]
  The MTD and/or RP2D of BBI-355 as a single agent and in combination with either erlotinib or futibatinib, will be determined.

Original Primary Outcome Measures (submitted: April 12, 2023)

• Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-355 [ Time Frame: 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 [ Time Frame: 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.

Current Secondary Outcome Measures (submitted: February 27, 2024)

• Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, and futibatinib [ Time Frame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) ]
  Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, and futibatinib will be determined.
• Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, and futibatinib [ Time Frame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) ]
  Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, and futibatinib will be determined.
• Time to Cmax (Tmax) of BBI-355, erlotinib, and futibatinib [ Time Frame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) ]
  Time to Cmax (Tmax) of BBI-355, erlotinib, and futibatinib will be determined.
• Area under the concentration time curve (AUC) of BBI-355, erlotinib, and futibatinib [ Time Frame: 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, erlotinib, and futibatinib will be determined.
• Anti-tumor activity of BBI-355 as a single agent and in combination with either erlotinib or futibatinib [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: April 12, 2023)

• Maximum observed plasma concentration (Cmax) of BBI-355 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

BBI-355 single agent dose escalation and expansion, and BBI-355 dose escalation in combination with select targeted therapies.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• 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

Intervention

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

Study Arms

• Experimental: Single Agent Dose Escalation
  Single agent BBI-355, administered orally in 28-day cycles
  Intervention: Drug: BBI-355
• Experimental: Single Agent Dose Expansion
  Single agent BBI-355, administered orally in 28-day cycles
  Intervention: Drug: BBI-355
• Experimental: Dose Escalation in Combination with EGFR Inhibitor
  Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.
  Interventions:

  • Drug: BBI-355
  • Drug: Erlotinib
• Experimental: Dose Escalation in Combination with FGFR Inhibitor
  Combination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles.
  Interventions:

  • Drug: BBI-355
  • Drug: Futibatinib

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 27, 2024): 150
• Original Estimated Enrollment (submitted: April 12, 2023): 47
• Estimated Study Completion Date: September 30, 2027
• Estimated Primary Completion Date: September 30, 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sara Weymer; 16198211090; ClinicalDevelopment@boundlessbio.com

Contact: Rebecca Reynolds; 16198211090; ClinicalDevelopment@boundlessbio.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05827614
• Other Study ID Numbers: BBI-355-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Boundless Bio
• Original Responsible Party: Same as current
• Current Study Sponsor: Boundless Bio
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Klaus Wagner, MD, PhD; Boundless Bio

• PRS Account: Boundless Bio
• Verification Date: February 2024