Description:
This is a first-in-human, Phase 1/2 open-label, multicenter, dose-escalation, safety, PK, and
biomarker study of PBI-200 in subjects with NTRK-fusion-positive advanced or metastatic solid
tumors.
Title
- Brief Title: Study of PBI-200 in Subjects With NTRK-Fusion-Positive Solid Tumors
- Official Title: A Phase 1/2 Study of PBI-200 in Subjects With NTRK-Fusion-Positive Advanced or Metastatic Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
PBI-200-101
- NCT ID:
NCT04901806
Conditions
- Solid Tumor, Adult
- Brain Tumor, Primary
- Desmoplastic Small Round Cell Tumor
Interventions
Drug | Synonyms | Arms |
---|
PBI-200 | | Phase 1 Dose Escalation |
Purpose
This is a first-in-human, Phase 1/2 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, Phase 1/2 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1 Dose Escalation | Experimental | | |
Phase 2 Cohort Expansion | Experimental | | |
Eligibility Criteria
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Phase 1: Number of patients with AEs |
Time Frame: | Through study completion, estimated as an average of 36 months |
Safety Issue: | |
Description: | Severity of AEs will be assessed according to the NCI CTCAE v5.0 |
Secondary Outcome Measures
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | Phase 1: ORR |
Time Frame: | Through study completion, estimated as an average of 36 months |
Safety Issue: | |
Description: | Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors |
Measure: | Duration of Response (DoR) |
Time Frame: | Through study completion, estimated as an average of 36 months |
Safety Issue: | |
Description: | Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors |
Measure: | Progression-free Survival |
Time Frame: | Through study completion, estimated as an average of 36 months |
Safety Issue: | |
Description: | Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Pyramid Biosciences |
Trial Keywords
- NTRK
- NTRK Fusion
- Resistance Mutation
Last Updated
August 2, 2021