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

NCT04901806 | Terminated Phase 1 FDA Drug

• 1 other identifier: PBI-200-101
• Study Type: interventional
• Target: 29
• Locations: 11 countries
• Sites: 42

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.

Conditions

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

Keywords

NTRK; NTRK Fusion; Resistance Mutation

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• 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

  Through study completion, estimated as an average of 36 months

• Duration of Response (DoR)

  Through study completion, estimated as an average of 36 months

• Progression-free Survival

  Through study completion, estimated as an average of 36 months

Study Arms (2)

Phase 1 Dose Escalation

EXPERIMENTAL

Drug: PBI-200

Phase 2 Cohort Expansion

EXPERIMENTAL

Drug: PBI-200

Interventions

PBI-200 DRUG

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

Phase 1 Dose Escalation; Phase 2 Cohort Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pyramid Biosciences: lead

Study Sites (42)

John Wayne Cancer Institute at St. Johns Health Center

Santa Monica, California, 90404, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Lake Mary, Florida, 32746, United States

Location

Sylvester Comprehensive Cancer Center (University of Miami)

Miami, Florida, 33136, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Westchester Medical Center

Hawthorne, New York, 10532, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Rigshospitalet, University Hospital of Copenhagen

Copenhagen, 2100, Denmark

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

CHU Poitiers - Hopital la Miletrie

Poitiers, 86000, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Dr. Senckenberg Institute of Neurooncology

Frankfurt am Main, 60528, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Marienhospital Herne

Herne, 44625, Germany

Location

Queen Mary Hospital

Pok Fu Lam, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Azienda Ospedaliero Universitaria delle Marche

Ancona, 60126, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione IRCCS Istituto Nazionale Tumori

Milan, 20133, Italy

Location

IRCCS (IEO) Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Napoli, 80131, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona

Verona, 37126, Italy

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Seoul National University Bundang Hosptial

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

The Catholic University of Korea St. Vincent Hosptial

Suwon, Gyeonggi-do, 16247, South Korea

Location

Severance Hosptial, Yonsei University Health System

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

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

Seoul, 06591, South Korea

Location

Hospital Universitari Vall d Hebron

Barcelona, 08035, Spain

Location

ICO l Hospitalet

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital General de Catalunya

Sant Cugat del Vallès, 08195, Spain

Location

The Christie

Manchester, M20 4BX, United Kingdom

Location

Royal Marsden Hospital Institute Cancer Research

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Brain Neoplasms; Desmoplastic Small Round Cell Tumor

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Study Officials

• Chief Medical Officer

  Pyramid Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 20, 2021
• First Posted: May 26, 2021
• Study Start: July 20, 2021
• Primary Completion: July 26, 2023
• Study Completion: July 26, 2023
• Last Updated: March 28, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1); FR (5); US (11); IT (6); KR (5); HK (2); GB (2); AU (1); DK (1); DE (3); ES (5)