Phase 1
N=46
(NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors
Gastrointestinal Stromal Tumors (GIST) · Other Relapsed or Refractory Solid Tumors
Bottom Line
View on ClinicalTrials.gov: NCT02508532 ↗Enrolled (actual)
46
Serious AEs
66.0%
Results posted
Jun 2021
Primary outcome: Primary: Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib — 0; 0; 0; 0 patients with event(s) of dose-limiting
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Avapritinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Blueprint Medicines Corporation
- Primary completion
- Mar 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) |
6; 6; 6; 6; 6; 3 | — |
| PRIMARY Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 |
36; 10; 20; 2; 40; 108 | — |
| SECONDARY Maximum Plasma Drug Concentration (Cmax) |
305; 343 | — |
| SECONDARY Time to Maximum Plasma Drug Concentration (Tmax) |
4.0; 4.02 | — |
| SECONDARY Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose (C24) |
134; 185 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC 0-24) |
4510; 5310 | — |
| SECONDARY Apparent Oral Clearance Unadjusted for Bioavailability (CL/F) |
31.5; 29.9 | — |
| SECONDARY Apparent Volume of Distribution, Unadjusted for Bioavailability (Vz/F) |
1310; 1340 | — |
| SECONDARY Terminal Elimination Half-life (t1/2) |
32.1; 43.5 | — |
| SECONDARY Maximum Plasma Drug Concentration (Cmax) at Steady State |
905; 1140 | — |
| SECONDARY Time of Maximal Concentration (Tmax) at Steady State |
4.0; 3.99 | — |
| SECONDARY Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at Steady State (C24,ss) |
593; 760 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-τ,ss) (τ=24 h) |
16900; 21300 | — |
| SECONDARY Progression-free Survival Per mRECIST Version 1.1 |
27.6; 5.5; 3.7 | — |
| SECONDARY Apparent Oral Clearance at Steady State, Unadjusted for Bioavailability (CLss/F) |
21.8; 22.8 | — |
| SECONDARY Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1 |
37; 26; 51; 1; 24; 77 | — |
| SECONDARY Response Rate Determined by Central Radiology Assessment Per Choi Criteria |
37; 18; 45; 1; 32; 83 | — |
| SECONDARY Duration of Response Determined by Central Radiology Assessment Per mRECIST, Version 1.1 |
22.1; 19.2; 10.2 | — |
| SECONDARY Median PFS on Last Prior Anti-cancer Therapy |
5.9; 31.0; 6.4 | — |
| SECONDARY Change From Baseline in Levels of KIT and PDGFRα Mutant Allele Fractions in Peripheral Blood |
8.702; 14.398 | — |
| SECONDARY KIT, PDGFRA, and Other Cancer-relevant Mutations Present in Tumor Tissue at Baseline and EOT |
— | — |
Summary
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).
Eligibility Criteria
Inclusion Criteria
- For Part 1: Histologically- or cytologically-confirmed diagnosis of unresectable GIST or another advanced solid tumor. Patients with unresectable GIST must have disease that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib or an experimental kinase-inhibitor agent, or disease with a D842 mutation in the PDGFRα gene. Patients with an advanced solid tumor other than GIST must have relapsed or refractory disease without an available effective therapy.
OR For Part 2:
- Group 1: Patients must have a confirmed diagnosis of unresectable GIST that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib, or an experimental kinase-inhibitor agent, and the patient does not have a D842V mutation in PDGFRα.
- Group 2: Patients must have a confirmed diagnosis of unresectable GIST with a D842V mutation in the PDGFRα gene. The PDGFRα mutation will be identified by local or central assessment, either in an archival tissue sample or a new tumor biopsy obtained prior to treatment with avapritinib.
- Group 3: Patients must have a confirmed diagnosis of unresectable GIST that has progressed and/or patients must have experienced intolerance to imatinib and not received additional kinase-inhibitor therapy. Patients must not have a known D842V mutation in PDGFRα.
- Groups 1, 2 and 3: At least 1 measurable lesion defined by mRECIST 1.1 for patients with GIST.
- Groups 1 and 2: A tumor sample (archival tissue or a new tumor biopsy) has been submitted for mutational testing.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Exclusion Criteria
- QT interval corrected using Fridericia's formula (QTcF) >450 milliseconds
- Platelet count 3 x the upper limit of normal (ULN) if no hepatic metastases are present; >5 × ULN if hepatic metastases are present
- Total bilirubin >1.5 × ULN; >3 × ULN with direct bilirubin, >1.5 × ULN in the presence of Gilbert's Disease
- Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min Brain malignancy or metastases to the brain
- History of a seizure disorder or requirement for anti-seizure medication
- Group 3: Patients known to be KIT wild type.
Data sourced from ClinicalTrials.gov (NCT02508532). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.