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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04901806
Recruitment Status : Recruiting
First Posted : May 26, 2021
Last Update Posted : May 11, 2023
Sponsor:
Information provided by (Responsible Party):
Pyramid Biosciences

Study Description
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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.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Brain Tumor, Primary Desmoplastic Small Round Cell Tumor Drug: PBI-200 Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
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
Official Title: A Phase 1/2 Study of PBI-200 in Subjects With NTRK-Fusion-Positive Advanced or Metastatic Solid Tumors
Actual Study Start Date : July 20, 2021
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase 1 Dose Escalation Drug: PBI-200
PBI-200 will be administered orally over continuous 28-day cycles
Experimental: Phase 2 Cohort Expansion Drug: PBI-200
PBI-200 will be administered orally over continuous 28-day cycles


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. Phase 1: Recommended Phase 2 Dose [ Time Frame: Approximately 12 months ]
  3. 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

  4. 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


Secondary Outcome Measures :
  1. 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 ]
  2. 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

  3. 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

  4. 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


Eligibility Criteria
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04901806


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

Locations
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Sponsors and Collaborators
Pyramid Biosciences
Investigators
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Study Director: Chief Medical Officer Pyramid Biosciences
More Information
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Additional Information:

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Responsible Party: Pyramid Biosciences
ClinicalTrials.gov Identifier: NCT04901806    
Other Study ID Numbers: PBI-200-101
First Posted: May 26, 2021    Key Record Dates
Last Update Posted: May 11, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pyramid Biosciences:
NTRK
NTRK Fusion
Resistance Mutation
Additional relevant MeSH terms:
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Neoplasms
Brain Neoplasms
Desmoplastic Small Round Cell Tumor
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
 Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type