Solid Tumor, AdultPhase 1NCT04901806
Study of PBI-200 in Subjects With NTRK-Fusion-Positive Solid Tumors
A Phase 1 study testing PBI-200 in people with Solid Tumor, Adult and Brain Tumor, Primary, run by Pyramid Biosciences at 42 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Adult, Brain Tumor, Primary, Desmoplastic Small Round Cell Tumor
- What is being tested?
- PBI-200
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 42 sitesin 11 countries
- Study dates
- 20 Jul 2021to 26 Jul 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
42 sites in 11 countries.
42 sites in 11 countries
United States11 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
Westchester Medical Center
Hawthorne, New York, 10532
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Florida Cancer Specialists
Lake Mary, Florida, 32746
Sylvester Comprehensive Cancer Center (University of Miami)
Miami, Florida, 33136
Miami Cancer Institute
Miami, Florida, 33176
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
John Wayne Cancer Institute at St. Johns Health Center
Santa Monica, California, 90404
Stanford Hospital and Clinics
Stanford, California, 94305
Italy6 sites
Azienda Ospedaliero Universitaria delle Marche
Ancona, 60126
IRCCS Ospedale San Raffaele
Milan, 20132
Fondazione IRCCS Istituto Nazionale Tumori
Milan, 20133
IRCCS (IEO) Istituto Europeo di Oncologia
Milan, 20141
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Naples, 80131
Azienda Ospedaliera Universitaria Integrata Verona
Verona, 37126
France5 sites
Institut Bergonie
Bordeaux, 33076
Centre Léon Bérard
Lyon, 69008
Hopital Europeen Georges Pompidou
Paris, 75015
CHU Poitiers - Hopital la Miletrie
Poitiers, 86000
Institut Gustave Roussy
Villejuif, 94805
South Korea5 sites
Seoul National University Bundang Hosptial
Seongnam-si, Gyeonggi-do, 13620
Severance Hosptial, Yonsei University Health System
Seoul, 03722
Samsung Medical Center
Seoul, 06351
The Catholic University of Korea Soul St. Mary's Hosptial
Seoul, 06591
The Catholic University of Korea St. Vincent Hosptial
Suwon, Gyeonggi-do, 16247
Spain5 sites
Hospital Universitari Vall d Hebron
Barcelona, 08035
ICO l Hospitalet
L'Hospitalet de Llobregat, 08908
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario La Paz
Madrid, 28046
Hospital General de Catalunya
Sant Cugat del Vallès, 08195
Germany3 sites
Dr. Senckenberg Institute of Neurooncology
Frankfurt am Main, 60528
Universitaetsklinikum Heidelberg
Heidelberg, 69120
Marienhospital Herne
Herne, 44625
Hong Kong2 sites
Queen Mary Hospital
Pok Fu Lam
Prince of Wales Hospital
Shatin
United Kingdom2 sites
The Christie
Manchester, M20 4BX
Royal Marsden Hospital Institute Cancer Research
Sutton, SM2 5PT
Denmark1 site
Rigshospitalet, University Hospital of Copenhagen
Copenhagen, 2100
About this study
Official title: 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.
Read the 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.
- Being tested
- PBI-200
- Keywords
- NTRK, NTRK Fusion, Resistance Mutation
- Medical subject headings
- Brain Neoplasms, Desmoplastic Small Round Cell Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBI-200Drug
PBI-200 will be administered orally over continuous 28-day cycles
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Dose Escalation | Experimental | Not described Receives: Drug: PBI-200 |
| Phase 2 Cohort Expansion | Experimental | Not described Receives: Drug: PBI-200 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of patients with AEs
Severity of AEs will be assessed according to the NCI CTCAE v5.0
Measured: Through study completion, estimated as an average of 36 months
Phase 1: Recommended Phase 2 Dose
Measured: Approximately 12 months
Phase 2: Cohort A - Overall Response Rate (ORR)
Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: Through study completion, estimated as an average of 36 months
Phase 2: Cohort B - ORR
Assessed using Response Assessment in Neuro-Oncology (RANO) criteria
Measured: 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
Measured: 29 days
Phase 1: ORR
Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors
Measured: 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
Measured: 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
Measured: Through study completion, estimated as an average of 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2021
- Study start20 Jul 2021
- Primary completion26 Jul 2023
- Study completion26 Jul 2023
Why it stopped: Sponsor terminated development of PBI-200
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pyramid Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Study director, Pyramid Biosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04901806
- Sponsor's protocol ID
- PBI-200-101
- Status last verified
- Mar 2024
- First submitted
- 20 May 2021
- Last updated
- 28 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of PBI-200 in Subjects With NTRK-Fusion-Positive Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT04901806
- Acronym / sponsor ID
- PBI-200-101
- Keywords
- NTRK, NTRK Fusion, Resistance Mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor terminated development of PBI-200
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Pyramid BiosciencesIndustry (pharma, biotech, devices)
- Study start
- 20 Jul 2021 (actual)
- Primary completion
- 26 Jul 2023 (actual)
- Study completion
- 26 Jul 2023 (actual)
- First posted
- 26 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Dose Escalation | Experimental | Drug: PBI-200 |
| Phase 2 Cohort Expansion | Experimental | Drug: PBI-200 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- 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.
Key exclusion criteria (3 listed)
- Cytotoxic chemotherapy, biologic agent, investigational agent, or radiation therapy ≤ 3 weeks prior to the first dose of PBI-200 (6 weeks for nitrosoureas).
- Small-molecule kinase inhibitors or hormonal agents ≤ 14 days and within 5 half-lives prior to the first dose of PBI-200.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PBI-200PBI-200 will be administered orally over continuous 28-day cycles | Drug | Phase 1 Dose Escalation, Phase 2 Cohort Expansion |
Primary outcome
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
Phase 1: Recommended Phase 2 Dose
Time frame: Approximately 12 months
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
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
4 secondary outcomes
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
Phase 1: ORR
Time frame: Through study completion, estimated as an average of 36 months
Duration of Response (DoR)
Time frame: Through study completion, estimated as an average of 36 months
Progression-free Survival
Time frame: Through study completion, estimated as an average of 36 months
Results and safety
The study was stopped early (reason given: Sponsor terminated development of PBI-200). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chief Medical Officer study director
Pyramid Biosciences
42 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PBI-200 in people with Solid Tumor, Adult and Brain Tumor, Primary, run by Pyramid Biosciences at 42 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in United States, Italy, France, South Korea, Spain and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor terminated development of PBI-200). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Number of patients with AEs (time frame: Through study completion, estimated as an average of 36 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2024.