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

Sponsor

Pyramid Biosciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04901806

Collaborator

(none)

Enrollment

Locations

Arms

34.4

Anticipated Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor, Adult Brain Tumor, Primary Desmoplastic Small Round Cell Tumor	Drug: PBI-200	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

74 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Study of PBI-200 in Subjects With NTRK-Fusion-Positive Advanced or Metastatic Solid Tumors

Actual Study Start Date :

Jul 20, 2021

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 Dose Escalation	Drug: PBI-200 PBI-200 will be administered orally over continuous 28-day cycles
Experimental: Phase 2 Cohort Expansion	Drug: PBI-200 PBI-200 will be administered orally over continuous 28-day cycles

Arm

Intervention/Treatment

Experimental: Phase 1 Dose Escalation

Drug: PBI-200

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

Experimental: Phase 2 Cohort Expansion

Drug: PBI-200

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

Outcome Measures

Primary Outcome Measures

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 1: Recommended Phase 2 Dose [Approximately 12 months]
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
Phase 2: Cohort B - ORR [Through study completion, estimated as an average of 36 months]
Assessed using Response Assessment in Neuro-Oncology (RANO) criteria

Secondary Outcome Measures

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]
Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John Wayne Cancer Institute at St. Johns Health Center	Santa Monica	California	United States	90404
2	Stanford Hospital and Clinics	Stanford	California	United States	94305
3	Sarah Cannon Research Institute at HealthONE	Denver	Colorado	United States	80218
4	Florida Cancer Specialists	Lake Mary	Florida	United States	32746
5	Sylvester Comprehensive Cancer Center (University of Miami)	Miami	Florida	United States	33136
6	Miami Cancer Institute	Miami	Florida	United States	33176
7	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
8	Westchester Medical Center	Hawthorne	New York	United States	10532
9	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
10	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
11	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
12	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
13	Seoul National University Bundang Hosptial	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
14	The Catholic University of Korea St. Vincent Hosptial	Suwon-si	Gyeonggi-do	Korea, Republic of	16247
15	Severance Hosptial, Yonsei University Health System	Seoul		Korea, Republic of	03722
16	Samsung Medical Center	Seoul		Korea, Republic of	06351
17	The Catholic University of Korea Soul St. Mary's Hosptial	Seoul		Korea, Republic of	06591