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

NCT ID: NCT04901806

Last Updated: 2024-03-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-20
• Study Completion Date: 2023-07-26

Brief Summary

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.

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Dose Escalation

Group Type: EXPERIMENTAL

PBI-200

Intervention Type: DRUG

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

Phase 2 Cohort Expansion

Group Type: EXPERIMENTAL

PBI-200

Intervention Type: DRUG

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

Interventions

PBI-200

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

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pyramid Biosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Medical Officer

Role: STUDY_DIRECTOR

Pyramid Biosciences

Locations

John Wayne Cancer Institute at St. Johns Health Center

Santa Monica, California, United States

Stanford Hospital and Clinics

Stanford, California, United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Florida Cancer Specialists

Lake Mary, Florida, United States

Sylvester Comprehensive Cancer Center (University of Miami)

Miami, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Westchester Medical Center

Hawthorne, New York, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Rigshospitalet, University Hospital of Copenhagen

Copenhagen, , Denmark

Institut Bergonie

Bordeaux, , France

Centre Léon Bérard

Lyon, , France

Hopital Europeen Georges Pompidou

Paris, , France

CHU Poitiers - Hopital la Miletrie

Poitiers, , France

Institut Gustave Roussy

Villejuif, , France

Dr. Senckenberg Institute of Neurooncology

Frankfurt am Main, , Germany

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

Marienhospital Herne

Herne, , Germany

Queen Mary Hospital

Pok Fu Lam, , Hong Kong

Prince of Wales Hospital

Shatin, , Hong Kong

Azienda Ospedaliero Universitaria delle Marche

Ancona, , Italy

IRCCS Ospedale San Raffaele

Milan, , Italy

Fondazione IRCCS Istituto Nazionale Tumori

Milan, , Italy

IRCCS (IEO) Istituto Europeo di Oncologia

Milan, , Italy

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Napoli, , Italy

Azienda Ospedaliera Universitaria Integrata Verona

Verona, , Italy

National Cancer Centre Singapore

Singapore, , Singapore

Seoul National University Bundang Hosptial

Seongnam-si, Gyeonggi-do, South Korea

The Catholic University of Korea St. Vincent Hosptial

Suwon, Gyeonggi-do, South Korea

Severance Hosptial, Yonsei University Health System

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea Soul St. Mary's Hosptial

Seoul, , South Korea

Hospital Universitari Vall d Hebron

Barcelona, , Spain

ICO l Hospitalet

L'Hospitalet de Llobregat, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital General de Catalunya

Sant Cugat del Vallès, , Spain

The Christie

Manchester, , United Kingdom

Royal Marsden Hospital Institute Cancer Research

Sutton, , United Kingdom

Countries

United States; Australia; Denmark; France; Germany; Hong Kong; Italy; Singapore; South Korea; Spain; United Kingdom

Other Identifiers

PBI-200-101

Identifier Type: -

Identifier Source: org_study_id