Study of PBI-200 in Subjects With NTRK-Fusion-Positive Solid Tumors
- Conditions
- Brain Tumor, PrimaryDesmoplastic Small Round Cell TumorSolid Tumor, Adult
- Interventions
- Registration Number
- NCT04901806
- Lead Sponsor
- Pyramid Biosciences
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 29
-
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
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1 Dose Escalation PBI-200 - Phase 2 Cohort Expansion PBI-200 -
- Primary Outcome Measures
Name Time Method Phase 2: Cohort B - ORR Through study completion, estimated as an average of 36 months Assessed using Response Assessment in Neuro-Oncology (RANO) criteria
Phase 1: Recommended Phase 2 Dose Approximately 12 months Phase 1: Number of patients with AEs Through study completion, estimated as an average of 36 months Severity of AEs will be assessed according to the NCI CTCAE v5.0
Phase 2: Cohort A - Overall Response Rate (ORR) Through study completion, estimated as an average of 36 months Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Secondary Outcome Measures
Name Time Method Phase 1: Area under the plasma drug concentration-time curve from 0 to 24 hours after one dose and after 28 doses 29 days Duration of Response (DoR) 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
Phase 1: ORR 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 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
Trial Locations
- Locations (42)
CHU Poitiers - Hopital la Miletrie
🇫🇷Poitiers, France
Centre Léon Bérard
🇫🇷Lyon, France
Hospital Universitari Vall d Hebron
🇪🇸Barcelona, Spain
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
John Wayne Cancer Institute at St. Johns Health Center
🇺🇸Santa Monica, California, United States
Florida Cancer Specialists
🇺🇸Lake Mary, Florida, United States
Stanford Hospital and Clinics
🇺🇸Stanford, California, United States
Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Sylvester Comprehensive Cancer Center (University of Miami)
🇺🇸Miami, Florida, 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
Institut Bergonie
🇫🇷Bordeaux, France
Rigshospitalet, University Hospital of Copenhagen
🇩🇰Copenhagen, Denmark
Hopital Europeen Georges Pompidou
🇫🇷Paris, France
ICO l Hospitalet
🇪🇸L'Hospitalet De Llobregat, Spain
Institut Gustave Roussy
🇫🇷Villejuif, France
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Dr. Senckenberg Institute of Neurooncology
🇩🇪Frankfurt am Main, Germany
Prince of Wales Hospital
ðŸ‡ðŸ‡°Sha Tin, Hong Kong
Azienda Ospedaliero Universitaria delle Marche
🇮🇹Ancona, Italy
Marienhospital Herne
🇩🇪Herne, Germany
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
IRCCS (IEO) Istituto Europeo di Oncologia
🇮🇹Milano, Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale
🇮🇹Napoli, Italy
Fondazione IRCCS Istituto Nazionale Tumori
🇮🇹Milano, Italy
The Catholic University of Korea St. Vincent Hosptial
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Azienda Ospedaliera Universitaria Integrata Verona
🇮🇹Verona, Italy
Seoul National University Bundang Hosptial
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Severance Hosptial, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
The Catholic University of Korea Soul St. Mary's Hosptial
🇰🇷Seoul, Korea, Republic of
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
The Christie
🇬🇧Manchester, United Kingdom
Hospital General de Catalunya
🇪🇸Sant Cugat Del Vallès, Spain
Royal Marsden Hospital Institute Cancer Research
🇬🇧Sutton, United Kingdom
Queen Mary Hospital
ðŸ‡ðŸ‡°Pok Fu Lam, Hong Kong