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

Solid Tumor, Adult Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04901806
• Other study ID #: PBI-200-101
• Status: Terminated
• Phase: Phase 1
• Start date: July 20, 2021
• Est. completion date: July 26, 2023

Study information

• Verified date: March 2024
• Source: Pyramid Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: July 26, 2023
• Est. primary completion date: July 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumor, Primary
• Desmoplastic Small Round Cell Tumor
• Neoplasms
• Solid Tumor, Adult

Intervention

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

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Denmark	Rigshospitalet, University Hospital of Copenhagen	Copenhagen
France	Institut Bergonie	Bordeaux
France	Centre Léon Bérard	Lyon
France	Hopital Europeen Georges Pompidou	Paris
France	CHU Poitiers - Hopital la Miletrie	Poitiers
France	Institut Gustave Roussy	Villejuif
Germany	Dr. Senckenberg Institute of Neurooncology	Frankfurt am Main
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Marienhospital Herne	Herne
Hong Kong	Queen Mary Hospital	Pok Fu Lam
Hong Kong	Prince of Wales Hospital	Sha Tin
Italy	Azienda Ospedaliero Universitaria delle Marche	Ancona
Italy	Fondazione IRCCS Istituto Nazionale Tumori	Milano
Italy	IRCCS (IEO) Istituto Europeo di Oncologia	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	IRCCS Istituto Nazionale Tumori Fondazione Pascale	Napoli
Italy	Azienda Ospedaliera Universitaria Integrata Verona	Verona
Korea, Republic of	Seoul National University Bundang Hosptial	Seongnam-si	Gyeonggi-do
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hosptial, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Soul St. Mary's Hosptial	Seoul
Korea, Republic of	The Catholic University of Korea St. Vincent Hosptial	Suwon-si	Gyeonggi-do
Singapore	National Cancer Centre Singapore	Singapore
Spain	Hospital Universitari Vall d Hebron	Barcelona
Spain	ICO l Hospitalet	L'Hospitalet De Llobregat
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital General de Catalunya	Sant Cugat Del Vallès
United Kingdom	The Christie	Manchester
United Kingdom	Royal Marsden Hospital Institute Cancer Research	Sutton
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	Westchester Medical Center	Hawthorne	New York
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Florida Cancer Specialists	Lake Mary	Florida
United States	Miami Cancer Institute	Miami	Florida
United States	Sylvester Comprehensive Cancer Center (University of Miami)	Miami	Florida
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	John Wayne Cancer Institute at St. Johns Health Center	Santa Monica	California
United States	Stanford Hospital and Clinics	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Pyramid Biosciences

Countries where clinical trial is conducted

United States,  Australia,  Denmark,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase 1: Recommended Phase 2 Dose		Approximately 12 months
Primary	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
Primary	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	Phase 1: Area under the plasma drug concentration-time curve from 0 to 24 hours after one dose and after 28 doses		29 days
Secondary	Phase 1: ORR	Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors	Through study completion, estimated as an average of 36 months
Secondary	Duration of Response (DoR)	Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors	Through study completion, estimated as an average of 36 months
Secondary	Progression-free Survival	Assessed by RECIST for subjects with non-brain primary tumors and by RANO for subjects with primary brain tumors	Through study completion, estimated as an average of 36 months