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Study of PBI-200 in Subjects With NTRK-Fusion-Positive Solid Tumors

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ClinicalTrials.gov Identifier: NCT04901806
Recruitment Status : Recruiting
First Posted : May 26, 2021
Last Update Posted : October 21, 2021
Sponsor:
Information provided by (Responsible Party):
Pyramid Biosciences

Tracking Information
First Submitted Date  ICMJE May 20, 2021
First Posted Date  ICMJE May 26, 2021
Last Update Posted Date October 21, 2021
Actual Study Start Date  ICMJE July 20, 2021
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2021)
  • Phase 1: Number of patients with AEs [ Time Frame: Through study completion, estimated as an average of 36 months ]
    Severity of AEs will be assessed according to the NCI CTCAE v5.0
  • Phase 1: Recommended Phase 2 Dose [ Time Frame: Approximately 12 months ]
  • Phase 2: Cohort A - Overall Response Rate (ORR) [ Time Frame: Through study completion, estimated as an average of 36 months ]
    Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Phase 2: Cohort B - ORR [ Time Frame: Through study completion, estimated as an average of 36 months ]
    Assessed using Response Assessment in Neuro-Oncology (RANO) criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2021)
  • Phase 1: Area under the plasma drug concentration-time curve from 0 to 24 hours after one dose and after 28 doses [ Time Frame: 29 days ]
  • Phase 1: ORR [ Time Frame: Through study completion, estimated as an average of 36 months ]
    Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors
  • Duration of Response (DoR) [ Time Frame: Through study completion, estimated as an average of 36 months ]
    Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors
  • Progression-free Survival [ Time Frame: Through study completion, estimated as an average of 36 months ]
    Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of PBI-200 in Subjects With NTRK-Fusion-Positive Solid Tumors
Official Title  ICMJE A Phase 1/2 Study of PBI-200 in Subjects With NTRK-Fusion-Positive Advanced or Metastatic Solid Tumors
Brief Summary This is a first-in-human, Phase 1/2 open-label, multicenter, dose-escalation, safety, PK, and biomarker study of PBI-200 in subjects with NTRK-fusion-positive advanced or metastatic solid tumors.
Detailed Description

This is a first-in-human, Phase 1/2 open-label, multicenter, dose-escalation, safety, PK, and biomarker study of PBI-200 in subjects with NTRK-fusion-positive advanced or metastatic solid tumors. Phase 1 will also include subjects with NTRK-amplified advanced or metastatic solid tumors or refractory EWSR1-WT1-fusion-positive desmoplastic small round cell tumors (DSRCTs).

Phase 1 is the dose-escalation portion of the study in which the evaluation of safety and tolerability and establishing the RP2D are primary objectives. Once the RP2D has been established, two expansion cohorts will open to accrual, a Non-Brain Primary Tumor cohort and a Primary Brian Tumor cohort.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Dose Escalation: Single-subject cohorts will be enrolled initially, until a subject has a Grade 2 or greater adverse event (AE), at which time a 3+3 design will be utilized. Dose escalation will continue until the maximum-tolerated dose (MTD) is reached, or the Recommended Phase 2 Dose (RP2D) is established.

Cohort Expansion: Two cohorts will be opened to accrual. Cohort A will enroll subjects with a non-brain primary tumor and Cohort B will enroll subjects with a primary brain tumor.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor, Adult
  • Brain Tumor, Primary
  • Desmoplastic Small Round Cell Tumor
Intervention  ICMJE Drug: PBI-200
PBI-200 will be administered orally over continuous 28-day cycles
Study Arms  ICMJE
  • Experimental: Phase 1 Dose Escalation
    Intervention: Drug: PBI-200
  • Experimental: Phase 2 Cohort Expansion
    Intervention: Drug: PBI-200
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 20, 2021)
74
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Subject has one of the following solid tumors which has progressed on or following at least one systemic therapy regimen administered for advanced or metastatic disease or for which no approved therapy exists:

    • NTRK-fusion-positive, locally advanced (i.e., not amenable to surgical resection) or metastatic solid tumor Note: Subjects with any grade of malignant glioma previously treated with systemic therapy are eligible.

Phase 1

  • NTRK-gene amplified, locally advanced or metastatic solid tumor
  • EWSR1-WT1-positive DSRCTs.
  • Subjects with NTRK-fusion-positive solid tumors other than primary brain tumors must have previously received treatment with a TRK inhibitor, unless the subject does not have access to TRK-inhibitor therapy (e.g., no TRK inhibitor is marketed and available to the subject in the subject's country) or the subject has declined treatment with available marketed TRK inhibitors.
  • Subjects with NTRK-gene amplified solid tumors, primary brain tumors or EWSR1-WT1-positive DSRCTs may have received prior treatment with a TRK inhibitor but this is not required.

Phase 2

  • Has measurable disease by RECIST v1.1 for subjects with non-brain primary tumors or RANO criteria for subjects with primary brain tumors.
  • Subjects with non-brain primary tumors must have previously received treatment with a TRK inhibitor and a documented resistance mutation(s) (e.g., solvent front, gatekeeper or xDFG mutation). Archival tissue from a prior biopsy taken after the subject completed TRK inhibitor treatment but prior to additional systemic therapy may be used to meet this eligibility criterion with Medical Monitor approval.
  • Subjects with primary brain tumors may have received prior treatment with a TRK inhibitor but this is not required. Biopsies of brain tumors are not required for eligibility.

Key Exclusion Criteria:

  • Cytotoxic chemotherapy, biologic agent, investigational agent, or radiation therapy ≤ 3 weeks prior to the first dose of PBI-200 (6 weeks for nitrosoureas).

    • Subjects with either primary brain tumors or brain metastasis must have completed brain radiation therapy 12 weeks prior to the brain MRI obtained within 4 weeks of the first dose of PBI-200.
  • Small-molecule kinase inhibitors or hormonal agents ≤ 14 days and within 5 half-lives prior to the first dose of PBI-200.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dir. Clinical Operations 650-283-3963 dchapman@pyramidbio.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04901806
Other Study ID Numbers  ICMJE PBI-200-101
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  ICMJE
Plan to Share IPD: No
Responsible Party Pyramid Biosciences
Study Sponsor  ICMJE Pyramid Biosciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Chief Medical Officer Pyramid Biosciences
PRS Account Pyramid Biosciences
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP