Lung NeoplasmsPhase 1NCT04862780
(SYMPHONY) Phase 1/2 Study Targeting EGFR Resistance Mechanisms in NSCLC
A Phase 1 study testing BLU-945 and osimertinib in people with Lung Neoplasms and Carcinoma, Non-Small-Cell Lung, run by Blueprint Medicines Corporation at 26 sites in 10 countries.
Trial summary
This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of BLU-945, a selective EGFR inhibitor, as monotherapy or in combination with osimertinib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms
- What is being tested?
- BLU-945 and osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 177 participants
- Where
- 26 sitesin 10 countries
- Study dates
- 29 Jun 2021to 7 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years of age at the time of signing the informed consent.
- Pathologically confirmed, definitively diagnosed, metastatic NSCLC harboring an activating EGFR mutation.
- Previously received at least 1 prior EGFR-targeted TKI with activity against the T790M mutation, such as osimertinib.
- Phase 1 Part 1B and Phase 2 Group 4: Patients must have experienced progressive disease while on osimertinib, and were able to tolerate prior osimertinib 80 mg QD dose.
- Tumor mutation profile determined locally via a Sponsor-approved testing methodology, using tumor tissue (ideally from a progressing lesion) and/or ctDNA in plasma. For Phase 1, it is preferable that samples used for analysis be obtained during or after disease progression on the last EGFR-targeted TKI received. For Phase 2, pre-treatment tumor sample must be obtained during or after disease progression on the last EGFR-targeted TKI received.
- Dose Escalation (Phase 1 Part 1A and Part 1B): At each dose level, slots may be reserved for patients with the mutations of interest.
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- BLU-945 Monotherapy Expansion Groups (Phase 2 Group 1, Group 2, and Group 3): Patients must have NSCLC harboring EGFR T790M and C797S mutation (Group 1); EGFR T790M but not C797S (Group 2); or EGFR C797S but not T790M (Group 3).
- BLU-945 with Osimertinib Expansion (Phase 2 Group 4): Slots may be reserved for patients with mutations of interest, but at least 12 slots will be allocated to patients with NSCLC harboring EGFR T790M and C797S mutation.
- Pretreatment tumor sample (either an archival sample or a sample obtained by pretreatment biopsy) submitted for central analysis. For Phase 1, it is preferable that pretreatment tumor samples be obtained from a progression lesion, during or after disease progression on the last EGFR-targeted TKI received. For Phase 2, pre-treatment tumor sample must be obtained during or after disease progression on the last EGFR-targeted TKI received.
- Patients without appropriate archival tissue available, where biopsy is not considered safe and/or medically feasible, may be discussed with the study medical monitor and may be approved for enrollment on a case-by-case basis.
- Phase 2 Expansion Groups: Patient has at least 1 measurable target lesion evaluable by RECIST 1.1 as assessed by the investigator.
- Eastern Cooperative Oncology Group (ECOG) performance status is 0-1.
- Agrees to use contraception consistent with the protocol and local regulations
Who cannot join
- Tumor harbors any additional known driver alterations (including but not limited to EGFR exon 20 insertion, or pathologic abnormalities of KRAS, BRAF V600E, NTRK1/2/3, HER2, ALK, ROS1, MET, or RET).
- NSCLC with mixed cell histology or a tumor with histologic transformation (NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition).
- Received the following anticancer therapy:
- EGFR-targeted TKI within 7 days prior to the first dose of study drug.
- Any immunotherapy or other antibody therapy (including EGFR-targeted antibodies or bi-specific antibodies) within 28 days prior to the first dose of study drug (immune-related toxicities must have resolved to < Grade 2 prior to starting BLU 945).
- Any other systemic anticancer therapy within 14 days or 5 half-lives prior to the first dose of study drug, whichever is the shortest, but with a minimum of 7 days in all circumstances. BLU 945 may be started within these washout periods if considered by the Investigator to be safe and within the best interest of the patient, with prior Sponsor approval.
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- Radiotherapy to a large field or including a vital organ (including whole brain radiotherapy or stereotactic radiosurgery to brain) within 14 days before the first dose of study drug. Participant received radiotherapy to a focal site of disease that did not include a vital organ (such as a limb) within 7 days before the first dose of study drug.
- CNS metastases or spinal cord compression that is associated with progressive neurological symptoms or requires increasing doses of corticosteroids to control the CNS disease. If a patient requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks preceding treatment. Asymptomatic CNS and leptomeningeal disease is allowed and, when measurable, should be captured as target lesions.
- Any of the following abnormalities on the most recent laboratory test prior to the first dose of study drug (ie, Cycle 1 Day 1 [C1D1] or screening):
- Absolute neutrophil count (ANC) <1.0×109/L.
- Platelet count <75×109/L.
- Hemoglobin ≤8.0 g/dL (red blood cell transfusion and erythropoietin may be used to reach at least 8.0 g/dL, but must have been administered at least 2 weeks prior to the first dose of study drug).
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3× 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 in presence of Gilbert's disease.
- Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min.
- International normalized ratio (INR) >2.3 or prothrombin time (PT) >6 seconds above control or a patient-specific INR or PT abnormality that the treating investigator considers clinically relevant and/or increases the risk for hemorrhage in that individual patient.
- Known intracranial hemorrhage and/or bleeding diatheses.
- Clinically active ongoing interstitial lung disease (ILD) of any etiology, including drug-induced ILD, and radiation pneumonitis within 28 days prior to initiation of study treatment. Patients with prior ILD associated with clinically resolved COVID 19 infection may be enrolled upon discussion with, and approval by, the Medical Monitor.
- Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or that have not resolved to baseline at the time of starting the study. Exceptions include alopecia and fatigue, and, upon discussion with and approval by the Medical Monitor, other toxicities that are not thought to present a risk to patient safety.
- Mean resting QT interval corrected using Fridericia's formula (QTcF) >450 msec, a history of prolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QT syndrome.
- Clinically significant, uncontrolled, cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias, including bradyarrhythmia that may cause QT prolongation (eg, Type II second degree heart block or third-degree heart block).
- History of another primary malignancy (other than completely resected carcinomas in situ) that has been diagnosed or required therapy within 2 years prior to initiation of study treatment. However, upon discussion with the Sponsor, the following categories of patients with prior malignancy are eligible to participate:
- Patients with a previous malignancy that completed all anticancer treatment at least 2 years before and with no evidence of residual disease from the prior malignancy at registration
- Patients who have another concurrent malignancy (not lung cancer) that is clinically stable and does not require tumor-directed treatment. (Examples include, but are not limited to, completely resected basal cell carcinoma and squamous cell carcinoma of skin, curatively treated prostate cancer, breast cancer and early gastric cancer cured by endoscopic mucosal resection or endoscopic submucosal dissection.)
- Active, uncontrolled infection (viral, bacterial, or fungal) or active tuberculosis, hepatitis B, hepatitis C, AIDS-related illness, or known COVID 19 infection. Controlled infections, including HIV and "cured" hepatitis C (no active fever, no evidence of systemic inflammatory response syndrome) that are stable on antiviral treatment may be eligible if benefit/risk is justified and permission is granted from the Sponsor.
- Dose-escalation (Parts 1A and 1B): Received neutrophil or platelet growth factor support within 14 days of the first dose of study drug.
- Requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration. BLU 945 may be started within 14 days or 5 half-lives of these therapies if considered by the Investigator to be safe and within the best interest of the patient, with prior Sponsor approval.
- Major surgical procedure within 14 days of the first dose of study drug (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
Trial locations and contacts
26 sites in 10 countries.
26 sites in 10 countries
United States10 sites
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, 90048
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
NYU Langone Health, Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
UC Irvine Health, Chao Family Comprehensive Cancer Center
Orange, California, 92868
South Korea5 sites
Seoul National University, Department of Internal Medicine
Seoul, 03080
Yonsei Cancer Center, Severance Hospital, Yonsei University
Seoul, 03722
Asan Medical Center, Department of Oncology
Seoul, 05505
Samsung Medical Center
Seoul, 06351
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591
Japan3 sites
National Cancer Center Hospital
Chuo Ku, Tokyo, 104-0045
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515
France2 sites
Institut Claudius Regaud (IUCT-O) - Cancer Comprehensive Center
Toulouse, 31059
Institut Gustave Roussy - DITEP
Villejuif, 94805
Netherlands1 site
The Netherlands Cancer Institute - Antoni van Leeuwenhoek
Amsterdam, 1066 CX
Spain1 site
Vall d'Hebron University Hospital, Oncology Department
Barcelona, 08035
United Kingdom1 site
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
About this study
Official title: A Phase 1/2 Study Targeting Acquired Resistance Mechanisms in Patients With EGFR Mutant Non-Small Cell Lung Cancer
This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of BLU-945, a selective EGFR inhibitor, as monotherapy or in combination with osimertinib.
Read the detailed description
The study will include an initial Phase 1 portion to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BLU-945 as monotherapy (initially in a QD regimen with the option to evaluate BID dosing, if supported by emerging PK and safety data), as well as an additional dose-escalation portion to determine the RP2D of BLU-945 in combination with osimertinib. The BLU-945 monotherapy Phase 2 expansion groups will consist of patients with tumors harboring specific mutation profiles (EGFR T790M and C797S mutation [Group 1]; EGFR T790M but not C797S [Group 2]; or EGFR C797S but not T790M [Group 3]). The BLU-945 with osimertinib Phase 2 expansion (Group 4) will include approximately 24 evaluable patients, with at least 12 slots reserved for patients with EGFR T790M and C797S mutation.
- Conditions
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms, Neoplasms, Neoplasms by Site, Lung Diseases
- Being tested
- BLU-945, osimertinib
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms, Neoplasms, Neoplasms by Site, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BLU-945Drug
Oral administration
osimertinibDrug
Also called Tagrisso
Osimertinib tablets for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Part 1A: BLU-945 as monotherapy | Experimental | Phase 1 dose escalation of BLU-945 as monotherapy at various dose levels Receives: Drug: BLU-945 |
| Part 1B: BLU-945 with osimertinib | Experimental | Phase 1 dose escalation of BLU-945 in combination with osimertinib 80 mg tablets for oral administration Receives: Drug: BLU-945; Drug: osimertinib |
| Phase 2, Group 1: BLU-945 as monotherapy | Experimental | Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR T790M and C797S mutations Receives: Drug: BLU-945 |
| Phase 2, Group 2: BLU-945 as monotherapy | Experimental | Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR T790M mutations Receives: Drug: BLU-945 |
| Phase 2, Group 3: BLU-945 as monotherapy | Experimental | Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR C797S mutations Receives: Drug: BLU-945 |
| Phase 2, Group 4: BLU-945 with osimertinib | Experimental | Phase 2 expansion group for BLU-945 with osimertinib at a dose determined during Part 1B in patients Receives: Drug: BLU-945; Drug: osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
[Phase 1] Determine the maximum tolerated dose (MTD) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
MTD determination: dose limiting toxicity (DLT) rate
Measured: Up to 12 months
[Phase 1] Rate and severity of adverse events of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Measured: Up to 12 months
[Phase 1] Determine recommended Phase 2 dose (RP2D) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
RP2D determination: DLT, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary safety and anticancer activity data
Measured: Up to 12 months
[Phase 2] Overall response rate (ORR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
ORR, defined as the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1
Measured: Up to 30 months
Secondary outcomes (21)
[Phase 1 and Phase 2] Cmax
Measured: Up to 42 months
[Phase 1 and Phase 2] Tmax
Measured: Up to 42 months
[Phase 1 and Phase 2] Tlast
Measured: Up to 42 months
[Phase 1 and Phase 2] AUC (0-24)
Measured: Up to 42 months
[Phase 1 and Phase 2] Ctrough
Measured: Up to 42 months
[Phase 1 and Phase 2] Vz/F
Measured: Up to 42 months
[Phase 1 and Phase 2] T 1/2
Measured: Up to 42 months
[Phase 1 and Phase 2] CL/F
Measured: Up to 42 months
[Phase 1] Overall response rate (ORR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
ORR, defined as the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1
Measured: Up to 12 months
[Phase 1 and Phase 2] Duration of response (DOR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
DOR, defined as the time from first documented response of complete response (CR) or partial response (PR) to the date of first documented progressive disease or death due to any cause, whichever occurs first
Measured: Up to 42 months
[Phase 1 and Phase 2] Accumulation ratio
Measured: Up to 42 months
[Phase 1 and Phase 2] Assess treatment-induced modulation of EGFR pathway biomarkers.
Profile pharmacodynamic changes in the EGFR pathway biomarker expression levels of dual specificity phosphatase (DUSP6) and sprouty RTK signaling antagonist 4 (SPRY4).
Measured: Up to 42 months
[Phase 2] Disease control rate (DCR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
DCR, defined as the proportion of patients who experience a best response of CR, PR, or stable disease (SD) according to RECIST 1.1
Measured: Up to 30 months
[Phase 2] Clinical benefit rate (CBR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
CBR, defined as the proportion of patients who experience a confirmed CR or PR, or stable disease (SD) with a duration of at least 16 weeks according to RECIST 1.1
Measured: Up to 30 months
[Phase 2] Progression free survival (PFS) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
PFS, defined as the time from the first dose of BLU-945 until the date of first documented progressive disease or death due to any cause, whichever occurs first
Measured: Up to 42 months
[Phase 2] Overall survival (OS) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
OS, defined as the time from the first dose of BLU-945 until the date of death due to any cause
Measured: Up to 42 months
[Phase 2] Central Nervous System Overall Response Rate (CNS-ORR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
CNS-ORR - proportion of patients with measurable (target) intracranial metastases at baseline who experience a confirmed intracranial CR or PR according to RECIST 1.1 principles
Measured: Up to 42 months
[Phase 2] Central Nervous System Duration of Response (CNS-DOR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
CNS-DOR - time from first documented intracranial CR or PR to the date of first documented intracranial PD
Measured: Up to 42 months
[Phase 2] Central Nervous System Progression Rate of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
CNS progression rate - proportion of patients with CNS progression as a component of first disease progression on study
Measured: Up to 42 months
[Phase 2] Rate and severity of adverse events of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Measured: Up to 42 months
[Phase 2] QTc Assessment
Effects of BLU-945 on ECG parameters extracted from continuous 12 lead Holter recordings
Measured: Up to 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2021
- Study start29 Jun 2021
- Primary completion7 Oct 2024
- Study completion7 Oct 2024
Why it stopped: Sponsor decision, not related to safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 177 participants (actual)
Sponsor and investigators
- Lead sponsor
- Blueprint Medicines Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04862780
- Sponsor's protocol ID
- BLU-945-1101
- Status last verified
- Feb 2025
- First submitted
- 21 Apr 2021
- Last updated
- 10 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study Targeting Acquired Resistance Mechanisms in Patients With EGFR Mutant Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT04862780
- Acronym / sponsor ID
- BLU-945-1101
- Conditions
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms, Neoplasms, Neoplasms by Site, Lung Diseases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision, not related to safety concerns
- Enrolment
- 177 participants (actual)
- Lead sponsor
- Blueprint Medicines CorporationIndustry (pharma, biotech, devices)
- Study start
- 29 Jun 2021 (actual)
- Primary completion
- 7 Oct 2024 (actual)
- Study completion
- 7 Oct 2024 (actual)
- First posted
- 28 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of BLU-945, a selective EGFR inhibitor, as monotherapy or in combination with osimertinib.
Detailed description
The study will include an initial Phase 1 portion to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BLU-945 as monotherapy (initially in a QD regimen with the option to evaluate BID dosing, if supported by emerging PK and safety data), as well as an additional dose-escalation portion to determine the RP2D of BLU-945 in combination with osimertinib. The BLU-945 monotherapy Phase 2 expansion groups will consist of patients with tumors harboring specific mutation profiles (EGFR T790M and C797S mutation [Group 1]; EGFR T790M but not C797S [Group 2]; or EGFR C797S but not T790M [Group 3]). The BLU-945 with osimertinib Phase 2 expansion (Group 4) will include approximately 24 evaluable patients, with at least 12 slots reserved for patients with EGFR T790M and C797S mutation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part 1A: BLU-945 as monotherapy | Experimental | Drug: BLU-945Phase 1 dose escalation of BLU-945 as monotherapy at various dose levels |
| Part 1B: BLU-945 with osimertinib | Experimental | Drug: BLU-945, Drug: osimertinibPhase 1 dose escalation of BLU-945 in combination with osimertinib 80 mg tablets for oral administration |
| Phase 2, Group 1: BLU-945 as monotherapy | Experimental | Drug: BLU-945Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR T790M and C797S mutations |
| Phase 2, Group 2: BLU-945 as monotherapy | Experimental | Drug: BLU-945Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR T790M mutations |
| Phase 2, Group 3: BLU-945 as monotherapy | Experimental | Drug: BLU-945Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR C797S mutations |
| Phase 2, Group 4: BLU-945 with osimertinib | Experimental | Drug: BLU-945, Drug: osimertinibPhase 2 expansion group for BLU-945 with osimertinib at a dose determined during Part 1B in patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- ≥18 years of age at the time of signing the informed consent.
- Pathologically confirmed, definitively diagnosed, metastatic NSCLC harboring an activating EGFR mutation.
- Previously received at least 1 prior EGFR-targeted TKI with activity against the T790M mutation, such as osimertinib.
- Tumor mutation profile determined locally via a Sponsor-approved testing methodology, using tumor tissue (ideally from a progressing lesion) and/or ctDNA in plasma. For Phase 1, it is preferable that samples used for analysis be obtained during or after disease progression on the last EGFR-targeted TKI received. For Phase 2, pre-treatment tumor sample must be obtained during or after disease progression on the last EGFR-targeted TKI received.
- Pretreatment tumor sample (either an archival sample or a sample obtained by pretreatment biopsy) submitted for central analysis. For Phase 1, it is preferable that pretreatment tumor samples be obtained from a progression lesion, during or after disease progression on the last EGFR-targeted TKI received. For Phase 2, pre-treatment tumor sample must be obtained during or after disease progression on the last EGFR-targeted TKI received.
Key exclusion criteria (28 listed)
- Tumor harbors any additional known driver alterations (including but not limited to EGFR exon 20 insertion, or pathologic abnormalities of KRAS, BRAF V600E, NTRK1/2/3, HER2, ALK, ROS1, MET, or RET).
- NSCLC with mixed cell histology or a tumor with histologic transformation (NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition).
- Received the following anticancer therapy:
- CNS metastases or spinal cord compression that is associated with progressive neurological symptoms or requires increasing doses of corticosteroids to control the CNS disease. If a patient requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks preceding treatment. Asymptomatic CNS and leptomeningeal disease is allowed and, when measurable, should be captured as target lesions.
- Any of the following abnormalities on the most recent laboratory test prior to the first dose of study drug (ie, Cycle 1 Day 1 [C1D1] or screening):
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BLU-945Oral administration | Drug | Part 1A: BLU-945 as monotherapy, Part 1B: BLU-945 with osimertinib, Phase 2, Group 1: BLU-945 as monotherapy, Phase 2, Group 2: BLU-945 as monotherapy, Phase 2, Group 3: BLU-945 as monotherapy, Phase 2, Group 4: BLU-945 with osimertinib |
| osimertinibAlso: TagrissoOsimertinib tablets for oral administration | Drug | Part 1B: BLU-945 with osimertinib, Phase 2, Group 4: BLU-945 with osimertinib |
Primary outcome
[Phase 1] Determine the maximum tolerated dose (MTD) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 12 months
MTD determination: dose limiting toxicity (DLT) rate
[Phase 1] Rate and severity of adverse events of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 12 months
[Phase 1] Determine recommended Phase 2 dose (RP2D) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 12 months
RP2D determination: DLT, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary safety and anticancer activity data
[Phase 2] Overall response rate (ORR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 30 months
ORR, defined as the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1
21 secondary outcomes
[Phase 1 and Phase 2] Cmax
Time frame: Up to 42 months
[Phase 1 and Phase 2] Tmax
Time frame: Up to 42 months
[Phase 1 and Phase 2] Tlast
Time frame: Up to 42 months
[Phase 1 and Phase 2] AUC (0-24)
Time frame: Up to 42 months
[Phase 1 and Phase 2] Ctrough
Time frame: Up to 42 months
[Phase 1 and Phase 2] Vz/F
Time frame: Up to 42 months
[Phase 1 and Phase 2] T 1/2
Time frame: Up to 42 months
[Phase 1 and Phase 2] CL/F
Time frame: Up to 42 months
[Phase 1] Overall response rate (ORR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 12 months
[Phase 1 and Phase 2] Duration of response (DOR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 42 months
[Phase 1 and Phase 2] Accumulation ratio
Time frame: Up to 42 months
[Phase 1 and Phase 2] Assess treatment-induced modulation of EGFR pathway biomarkers.
Time frame: Up to 42 months
[Phase 2] Disease control rate (DCR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 30 months
[Phase 2] Clinical benefit rate (CBR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 30 months
[Phase 2] Progression free survival (PFS) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 42 months
[Phase 2] Overall survival (OS) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 42 months
[Phase 2] Central Nervous System Overall Response Rate (CNS-ORR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 42 months
[Phase 2] Central Nervous System Duration of Response (CNS-DOR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 42 months
[Phase 2] Central Nervous System Progression Rate of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 42 months
[Phase 2] Rate and severity of adverse events of BLU-945 as monotherapy and BLU-945 in combination with osimertinib
Time frame: Up to 42 months
[Phase 2] QTc Assessment
Time frame: Up to 25 months
Results and safety
The study was stopped early (reason given: Sponsor decision, not related to safety concerns). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
26 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BLU-945 and osimertinib in people with Lung Neoplasms and Carcinoma, Non-Small-Cell Lung, run by Blueprint Medicines Corporation at 26 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, South Korea, Japan, France, Canada and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor decision, not related to safety concerns). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
[Phase 1] Determine the maximum tolerated dose (MTD) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib (time frame: Up to 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2025.