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

• ClinicalTrials.gov Identifier: NCT04901806
• Recruitment Status: Recruiting
• First Posted: May 26, 2021
• Last Update Posted: May 11, 2023
• Sponsor: Pyramid Biosciences
• Information provided by (Responsible Party): Pyramid Biosciences

Tracking Information

• First Submitted Date: May 20, 2021
• First Posted Date: May 26, 2021
• Last Update Posted Date: May 11, 2023
• Actual Study Start Date: July 20, 2021
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of PBI-200 in Subjects With NTRK-Fusion-Positive Solid Tumors
• Official Title: 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: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

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

• Solid Tumor, Adult
• Brain Tumor, Primary
• Desmoplastic Small Round Cell Tumor

Intervention

Drug: PBI-200

PBI-200 will be administered orally over continuous 28-day cycles

Study Arms

• Experimental: Phase 1 Dose Escalation
  Intervention: Drug: PBI-200
• Experimental: Phase 2 Cohort Expansion
  Intervention: Drug: PBI-200

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 20, 2021): 74
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

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

Contacts

Contact: Mel McMahon; 888-850-0650; support+nct@sparkcures.com

• Listed Location Countries: Australia, Denmark, France, Germany, Hong Kong, Italy, Korea, Republic of, Singapore, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04901806
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Pyramid Biosciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Pyramid Biosciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Chief Medical Officer; Pyramid Biosciences

• PRS Account: Pyramid Biosciences
• Verification Date: May 2023