Neoplasms

Immune System Diseases

All Conditions

Blood and Lymph Conditions

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Behaviors and Mental Disorders

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

Mastocytosis

Leukemia

Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Renal Insufficiency

Glioma

Sarcoma

Lung Neoplasms

Gastrointestinal Stromal Tumors

Aggression

Mastocytosis, Systemic

Mast Cell Activation Disorders

Leukemia, Mast-Cell

Ichthyosis, X-Linked

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Soft Tissue Sarcoma

Germ Cells Tumors

Penile Cancer

Systemic Mastocytosis

Escalation Phase: DCC-2618 tablets in escalating dose cohorts given orally BID (twice daily) every 12 hours or once daily (QD) for repeated 28-day cycles. Participants may continue to receive study drug until discontinuation criteria are met. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received 3 prior therapies. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received 4 prior therapies. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received at least one prior therapy and no more than 2 prior therapies. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with systemic mastocytosis and other hematologic malignancies.\[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with malignant gliomas.\[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with other solid tumors. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with melanomas. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with soft tissue sarcomas.\[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with germ cell, penile cancer and non-small cell lung carcinoma (NSCLC). \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST and other solid tumors with renal impairment. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles for active patients from the Escalation and Extension Phases.

DCC-2618

Deciphera Pharmaceuticals, LLC

This is a Phase 1, open-label, first-in-human (FIH) dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of DCC-2618, administered orally (PO), in adult patients with advanced malignancies. The study consists of 2 parts, a dose-escalation phase, and an expansion phase. All active patients (from both dose-escalation and expansion phases) will then transition into an extension phase.

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

A Multicenter Phase 1, Open-Label Study of DCC-2618 to Assess Safety, Tolerability, Efficacy, and Pharmacokinetics in Patients With Advanced Malignancies

Dose limiting toxicities, AEs, SAEs, discontinuation of drug due to toxicity, physical exams and ECOG PS, ophthalmologic examinations, changes from baseline in laboratory parameters, electrocardiograms, LVEF, and vital signs.

Objective response rate (ORR); Disease control rate (DCR)

Deciphera Pharmaceuticals LLC

Connective Tissue Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Sunitinib

Tyrosine Kinase Inhibitors

Imatinib Mesylate

Tyrosine

Participants with unresectable or metastatic GIST who will receive orally administered THE-630.

Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase.

Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib and 0-1 additional lines of therapy in the advanced/metastatic setting, who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase.

Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib (including in the adjuvant setting) and who have not received additional systemic therapy for advanced GIST, who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase.

Oral THE-630 administered once daily in a continuous regimen

THE-630

Stew Kroll

This study will assess the safety, efficacy, and pharmacokinetics of THE-630 in participants with advanced gastrointestinal stromal tumors (GIST).

The drug being tested in this study is called THE-630, an orally administered KIT tyrosine kinase inhibitor. The study will be conducted in two parts: a dose escalation phase, followed by an expansion phase. The patient population of the initial dose escalation phase (Phase 1) of the trial will include patients with unresectable or metastatic GIST. Patients must have disease progression on or be intolerant to imatinib therapy and have also received at least 1 of the following: sunitinib, regorafenib, ripretinib, or avapritinib. The primary objective of the dose escalation phase is to determine the safety profile of oral THE-630, including the dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and the recommended Phase 2 dose (RP2D).

Once a recommended dose has been determined in the escalation phase, the expansion phase (Phase 2) will enroll 3 cohorts of patients with unresectable or metastatic GIST defined by prior therapy:

* Cohort 1: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib (≥5th Line).
* Cohort 2: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib and 0-1 additional lines of therapy in the advanced/metastatic setting (3rd-4th Line).
* Cohort 3: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib (including in the adjuvant setting) and who have not received additional systemic therapy for advanced GIST (2nd Line).

The safety and tolerability of orally administered THE-630 will continue to be assessed in the expansion cohorts. However, the primary objective of the expansion component of the trial is to evaluate the anti-tumor activity of THE-630 in these GIST patient populations.

A Study of THE-630 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)

A Phase 1/2 Study of the Safety, Pharmacokinetics and Anti-Tumor Activity of the Oral KIT Inhibitor THE-630 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)

Cmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses

Tmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses

AUC 0-24 of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses

AUC 0-t of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses

Theseus Pharmaceuticals

Avapritinib will be administered orally at 300 mg QD.

Avapritinib

Blueprint Medicines

This record comprises the currently available Expanded Access Programs (EAP) for avapritinib (BLU-285):

1) A Post Trial Access (PTA) program to provide continued access to treatment with avapritinib to BLU-285-1107 participants with solid tumors who are unable to access commercially available avapritinib after trial BLU-285-1107 (NCT04908176) has ended.

Expanded Access Program for Avapritinib

Expanded Access Program (EAP) for Avapritinib

Blueprint Medicines Corporation

Part 1: Patients received a starting dose of 30 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 60 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 90 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 135 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 200 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation. .

Part 1: Patients received a starting dose of 300 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation. Patients that received at least one dose of avapritinib were included in the Part 2 analysis.

Part 1: Patients received a starting dose of 400 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Patients that received at least one dose of avapritinib were included in the Part 2 analysis.

Part 1: Patients received a starting dose of 600 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1 and Part 2: Patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD were included in the Part1/Part 2 safety and efficacy analysis.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (formerly BLU-285), administered orally (PO), in adult patients with unresectable GIST or other relapsed or refractory solid tumors. The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).

(NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors

A Phase 1 Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors

Patients with event(s) of dose-limiting toxicity

The overall safety profile of the drug was assessed by reviewing the number of patients with AEs, SAEs and other events. There was no formal statistical analysis. Safety assessments continued for the duration of treatment.

To evaluate objective response rate (ORR) determined by central radiology assessment per mRECIST, version 1.1 in patients with advanced GIST treated with avapritinib. A complete response per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Overall Response (OR) = CR + PR

Maximum plasma drug concentration (Cmax) following a single dose of avapritinib

Cycle 1 Day 1 PK time to maximum plasma drug concentration (Tmax)

Plasma drug concentration at 24 hours postdose prior to the next daily dose (C24) following a single dose of avapritinib

Area under the plasma concentration-time curve from time 0 to 24 hours (AUC 0-24) following a single dose of avapritinib

Apparent oral clearance unadjusted for bioavailability (CL/F) following a single dose of avapritinib

Apparent volume of distribution, unadjusted for bioavailability (Vz/F) following a single dose of avapritinib

Terminal elimination half-life (t1/2) following a single dose of avapritinib

Maximum plasma drug concentration (Cmax) at steady state following 15 days of QD dosing

Time of maximal concentration (Tmax) at steady state following 15 days of QD dosing

Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at steady state (C24,ss) following 15 days of QD dosing

Area under the plasma concentration-time curve over the dosing interval at steady sate (AUC0-τ,ss) (τ=24 h) following 15 days of QD dosing

Progression-free survival is defined as the time in months from the start of treatment to the date of first documented progression or death due to any cause. Progression-free survival determined by central radiological assessment per modified Response Evaluation Criteria in Solid Tumors (mRECIST), version 1.1 in patients with advanced GIST. A progressively growing tumor must meet the following criteria: a) the target lesions must be greater or equal to 2cm in size and be a new GIST active lesion or b) the target lesions must be expanding on at least 2 sequential imaging studies.

Apparent oral clearance at steady state, unadjusted for bioavailability (CLss/F) following 15 days of QD dosing

Percent of patients with a complete response, partial response or stable disease lasting more than 16 weeks. A complete response per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Stable disease is defined as a tumor that does not meet the criteria for progression or for response. A progressively growing tumor must meet the following criteria: a) the target lesions must be greater or equal to 2cm in size and be a new GIST active lesion or b) the target lesions must be expanding on at least 2 sequential imaging studies.

A complete response is defined as complete disappearance of all target lesions. A partial response is ≥10% decrease tumor size at computed tomography (CT) or ≥15% decrease in tumor attenuation at computed tomography (CT) and no new lesions. The response rate is defined as complete response plus partial response.

Duration from time to first documented CR/PR to date of first documented disease progression or death.

A complete response per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Overall Response (OR) = CR + PR

Progression Free Survival (PFS) is defined as the time in months from the start of treatment to the date of first documented disease progression or death due to any cause, which ever occurs first. PFS on last prior anti-cancer therapy is defined as the time in months from the start of last prior anti-cancer therapy to progression on that therapy.

Change of mutant allele fraction (MAF) summarizes the largest fold change. Change from baseline only displayed for patients with pre and post treatment MAF measurements. A positive number represents an increase in MAF. Data is only provided for patients that had both a baseline measurement and an end of treatment measurement.

Change in mutations in tumor tissue at baseline and end of treatment (EOT). EOT tumor biopsies were optional and there were no EOT samples collected.

Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD

Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD

Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD

Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD

Part 1: Patients received a starting dose of 200 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD

Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD

Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 or 400 mg QD

Part 1 and Part 2: Patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD were included in the Part1/Part 2 safety and efficacy analysis.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Includes 13 patients from Part 1

Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 mg or 400 mg QD

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Belgium

France

Germany

Netherlands

Poland

South Korea

Spain

United Kingdom

United States

Region of Enrollment

Body Mass Index was only calculated for patients with both a height and weight measurement at Baseline

Body Mass Index (BMI)

Medical Information

Experimental: Part 1 Avapritinib (Formerly BLU-285) 300 mg QD

Experimental: Part 1 Avapritinib (Formerly BLU-285) 400 mg QD

Patients that completed Part 1 or had a DLT

Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib

Participants with an Adverse Event

Participants with a Serious Adverse Event

Part 1 and Part 2: Patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD were included in the Part1/Part 2 safety and efficacy analysis. 13 patients in this group were enrolled in Part 1

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 mg or 400 mg QD

Safety Population - all patients that received at least one dose of avapritinib

Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE)

Patients with a PDGFRA D842V Mutation, any line of treatment

Patients With a PDGFRA D842V Mutation

Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy

2L Patients Without a PDGFRA D842V Mutation

Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy

3L Patients Without a PDGFRA D842V Mutation

patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg, including 13 patients enrolled in Part 1

Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1

Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1 Avapritinib (Formerly BLU-285) 300 mg QD

Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1 Avapritinib (Formerly BLU-285) 400 mg QD

Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK

Maximum Plasma Drug Concentration (Cmax)

Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD

Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD

Patients enrolled in Part 1 and Part 2 with available samples for PK

Time to Maximum Plasma Drug Concentration (Tmax)

Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples

Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose (C24)

Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC 0-24)

Apparent Oral Clearance Unadjusted for Bioavailability (CL/F)

Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available PK samples

Apparent Volume of Distribution, Unadjusted for Bioavailability (Vz/F)

Terminal Elimination Half-life (t1/2)

Maximum Plasma Drug Concentration (Cmax) at Steady State

Time of Maximal Concentration (Tmax) at Steady State

Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at Steady State (C24,ss)

Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-τ,ss) (τ=24 h)

Patients with a PDGFRA D842V mutation, any line of treatment

Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD

Progression-free Survival Per mRECIST Version 1.1

Apparent Oral Clearance at Steady State, Unadjusted for Bioavailability (CLss/F)

patients with a starting dose of 300 or 400 mg QD

Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1

Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg

Response Rate Determined by Central Radiology Assessment Per Choi Criteria

Patients With PDGFRA D842V Mutation

Patients in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD. Only patients that achieved a CR or PR are included in this analysis

Duration of Response Determined by Central Radiology Assessment Per mRECIST, Version 1.1

Patients enrolled on any dose (Part 1 and Part 2) with data on progression-free survival for the most recent prior therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies	NCT02571036	Gastrointestina... Advanced System... Advanced Cancer...	DCC-2618 DCC-2618	18 Years -	Deciphera Pharmaceuticals LLC
A Study of THE-630 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)	NCT05160168	Gastrointestina... Neoplasms, Conn... Neoplasms, Conn... Neoplasms by Hi... Neoplasms Gastrointestina... Digestive Syste... Digestive Syste... Gastrointestina...	THE-630	18 Years -	Theseus Pharmaceuticals
Expanded Access Program for Avapritinib	NCT04714086	Solid Tumors	Avapritinib	18 Years -	Blueprint Medicines Corporation
(NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors	NCT02508532	Gastrointestina... Other Relapsed ...	Avapritinib	18 Years -	Blueprint Medicines Corporation
Efficiency of Imatinib Treatment After 10 Years of Treatment in Patients With Gastrointestinal Stromal Tumours (GIST) (Gist-Ten)	NCT05009927	Metastatic Gast... C-KIT Mutation Advanced Gastro...	Imatinib tablet...	18 Years -	Centre Leon Berard
A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies	NCT02571036	Gastrointestina... Advanced System... Advanced Cancer...	DCC-2618 DCC-2618	18 Years -	Deciphera Pharmaceuticals LLC
Expanded Access Program for Avapritinib	NCT04714086	Solid Tumors	Avapritinib	18 Years -	Blueprint Medicines Corporation
Phase II Study of Sunitinib Malate for Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma	NCT00400569	Liposarcoma Leiomyosarcoma Fibrosarcoma Malignant Fibro...	Sunitinib Malat...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for gastrointestinal stromal tumors (gist)