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

A Phase 1/2 Study of PBI-200 in Subjects With NTRK-Fusion-Positive Advanced or Metastatic Solid Tumors

This is a first-in-human, open-label, multicenter, dose-escalation, safety, PK, and biomarker study of PBI-200 in subjects with NTRK-fusion-positive advanced or metastatic solid tumors.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor, Adult; Desmoplastic Small Round Cell Tumor; Brain Tumor, Primary
• Intervention / Treatment: Drug: PBI-200

Detailed Description

This is a first-in-human, 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.

Although this was intended to be a Phase 1/2 trial, the trial was terminated without proceeding to Phase 2.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mel McMahon; Phone Number: 888-850-0650; Email: support+nct@sparkcures.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Centre
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, University Hospital of Copenhagen
• France
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Lyon, France, 69008
    • Centre Leon Bérard
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou
  • Poitiers, France, 86000
    • CHU Poitiers - Hôpital la Milétrie
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Frankfurt am Main, Germany, 60528
    • Dr. Senckenberg Institute of Neurooncology
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Herne, Germany, 44625
    • Marienhospital Herne
• Hong Kong
  • Pok Fu Lam, Hong Kong
    • Queen Mary Hospital
  • Sha Tin, Hong Kong
    • Prince of Wales Hospital
• Italy
  • Ancona, Italy, 60126
    • Azienda Ospedaliero Universitaria delle Marche
  • Milano, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale Tumori
  • Milano, Italy, 20141
    • IRCCS (IEO) Istituto Europeo di Oncologia
  • Napoli, Italy, 80131
    • IRCCS Istituto Nazionale Tumori Fondazione Pascale
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata Verona
• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hosptial, Yonsei University Health System
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea Soul St. Mary's Hosptial
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hosptial
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 16247
      • The Catholic University of Korea St. Vincent Hosptial
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall D Hebron
  • L'Hospitalet De Llobregat, Spain, 08908
    • ICO l Hospitalet
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Sant Cugat Del Vallès, Spain, 08195
    • Hospital General de Catalunya
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital Institute Cancer Research
• United States
  • California
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute at St. Johns Health Center
    • Stanford, California, United States, 94305
      • Stanford Hospital and Clinics
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Florida Cancer Specialists
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center (University of Miami)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • New York
    • Hawthorne, New York, United States, 10532
      • Westchester Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Number of patients with AEs	Severity of AEs will be assessed according to the NCI CTCAE v5.0	Through study completion, estimated as an average of 36 months
Phase 1: Recommended Phase 2 Dose		Approximately 12 months
Phase 2: Cohort A - Overall Response Rate (ORR)	Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Through study completion, estimated as an average of 36 months
Phase 2: Cohort B - ORR	Assessed using Response Assessment in Neuro-Oncology (RANO) criteria	Through study completion, estimated as an average of 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Area under the plasma drug concentration-time curve from 0 to 24 hours after one dose and after 28 doses		29 days
Phase 1: ORR	Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors	Through study completion, estimated as an average of 36 months
Duration of Response (DoR)	Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors	Through study completion, estimated as an average of 36 months
Progression-free Survival	Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors	Through study completion, estimated as an average of 36 months

Collaborators and Investigators

• Sponsor: Pyramid Biosciences
• Investigators: Study Director: Chief Medical Officer, Pyramid Biosciences

Publications and helpful links

Helpful Links

• Click here to learn more about the PBI-200-101 trial

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): July 26, 2023
• Study Completion (Actual): July 26, 2023

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: NTRK; NTRK Fusion; Resistance Mutation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Sarcoma; Neoplasms; Brain Neoplasms; Desmoplastic Small Round Cell Tumor
• Other Study ID Numbers: PBI-200-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No