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(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC

Primary Purpose

Lung Neoplasm, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BLU-701
osimertinib
carboplatin
pemetrexed
Sponsored by
Blueprint Medicines Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Neoplasm focused on measuring Targeted therapy, EGFR, NSCLC, non-small cell lung cancer, EGFR mutant NSCLC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. ≥18 years of age at the time of signing the informed consent.
  2. Pathologically confirmed metastatic NSCLC.
  3. Tumor mutation profile determined locally via next generation sequencing (NGS), using tumor tissue (preferably 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, samples used for analysis must be obtained during or after disease progression on the last EGFR-targeted TKI received.

    1. All Parts: activating EGFR mutation (Ex19Del or L858R)
    2. Part 2A: Tumor must additionally harbor an EGFR C797X resistance mutation.
  4. Previously received:

    1. Part 1A and 2A: At least 1 prior third-generation EGFR-targeted TKI, such as osimertinib
    2. Part 1B: Patients must have experienced progressive disease while on osimertinib, were able to tolerate prior osimertinib 80 mg QD dose, and continuing on osimertinib is deemed to be in the patient's best interests in the opinion of the Investigator.

      Patients who have discontinued osimertinib may be eligible, if no more than 6 weeks elapse between the discontinuation of prior osimertinib and resumption of osimertinib on study.

    3. Part 1C: At least 1 prior EGFR-targeted TKI
  5. Willing to provide pretreatment tumor sample (either an archival sample or a sample obtained by pretreatment biopsy. For Phase 1, it is preferable that pretreatment tumor sample be obtained from a progressing lesion and during or after disease progression on the last EGFR-targeted TKI received. For Phase 2, pretreatment tumor sample must be obtained during or after disease progression on the last EGFR-targeted TKI treatment 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 approved for enrollment on a case-by-case basis.
  6. Part 2A: at least 1 measurable target lesion per RECIST 1.1 as assessed by the Investigator
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  8. Agrees to use contraception consistent with local regulations

Exclusion Criteria:

  1. Have disease that is suitable for local therapy administered with curative intent.
  2. Have tumor that harbors EGFR T790M mutation or any additional known driver alterations (including but not limited to, EGFR exon 20 insertions, or pathologic abnormalities of KRAS, BRAF V600E, NTRK1/2/3, HER2, ALK, ROS1, MET, or RET).
  3. Have NSCLC with mixed cell histology or a tumor with known histologic transformation (NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition).
  4. Have received the following anticancer therapy:

    1. Any third-generation EGFR TKI (such as osimertinib) within 7 days prior to the planned first dose of study drug. Note: patients in Part 1B do not require a wash-out period for osimertinib.
    2. Part 2A: Previous therapy with first- or second-generation EGFR TKI, such as erlotinib, gefitinib, afatinib or dacomitinib.
    3. Part 1C: Prior platinum-based chemotherapy for advanced or metastatic disease.
    4. Any immunotherapy or other antibody therapy (including EGFR-targeted antibodies or bi-specific antibodies) within 21 days prior to the first dose of study drug.
    5. 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-701 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.
  5. 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. 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.
  6. Have 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.
  7. Have any of the following laboratory abnormalities on last laboratory assessment prior to initiation of study drug (i.e., C1D1 or Screening):

    1. Absolute neutrophil count (ANC) <1.0×109/L (for patients in Part 1C: <1.5×109/L)
    2. Platelet count <75×109/L (for patients in Part 1C: <100×109/L)
    3. 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).
    4. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5× the upper limit of normal (ULN) if no hepatic metastases are present; >5× ULN if hepatic metastases are present.
    5. Total bilirubin >1.5× ULN; >3× ULN in presence of Gilbert's disease.
    6. Estimated (Cockroft-Gault formula, Appendix 1) or measured creatinine clearance <60 mL/min.
    7. International normalized ratio (INR) >2.3 or prothrombin time (PT) >6 seconds above ULN 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.
  8. Have known intracranial hemorrhage and/or bleeding diatheses.
  9. Have 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. Grade 1 asymptomatic ILD is not exclusionary.
  10. Have 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.
  11. Have 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.
  12. Have 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 (e.g., Type II second degree heart block or third degree heart block).
  13. Have 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, patients who have another concurrent malignancy (not lung cancer) that is clinically stable and does not require tumor-directed treatment may be eligible to participate. 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.
  14. Have active, uncontrolled infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B, hepatitis C, AIDS-related illness, or COVID19 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 are not exclusionary.
  15. For Parts 1A, 1B, and 1C: have received neutrophil or platelet growth factor support within 14 days of the first dose of study drug.
  16. Require treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration. BLU-701 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.
  17. Have 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).

Sites / Locations

  • Dana-Farber Cancer Institute
  • Henry Ford Hospital
  • New York University (NYU) Langone Medical Center
  • Memorial Sloan Kettering Cancer Center
  • Sarah Cannon Research Institute
  • NEXT Virginia
  • Seattle Cancer Care Alliance

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1A: BLU-701 as monotherapy

Part 1B: BLU-701 with osimertinib

Part 1C: BLU-701 with platinum-based chemotherapy

Part 2A: BLU-701 as monotherapy

Arm Description

Phase 1 dose escalation of BLU-701 as monotherapy at various dose levels

BLU-701 in combination with osimertinib 40 mg or 80 mg tablets for oral administration

BLU-701 in combination with platinum-based chemotherapy (carboplatin and pemetrexed): Carboplatin - IV infusion dosed to target AUC of 5-6 mg/mL min q3w Pemetrexed - IV infusion dosed to 500 mg/m2 q3w

Phase 2 expansion group for BLU-701 as monotherapy at a dose determined during Part 1A in patients harboring the EGFR C797X resistance mutation

Outcomes

Primary Outcome Measures

[Phase 1] Determine the maximum tolerated dose (MTD) of BLU-701 monotherapy, BLU-701 in combination with osimertinib, and BLU-701 in combination with platinum-based chemotherapy
MTD determination: dose limiting toxicity (DLT) rate
[Phase 1] Determine the recommended Phase 2 dose (RP2D) of BLU-701 monotherapy, BLU-701 in combination with osimertinib, and BLU-701 in combination with platinum-based chemotherapy
RP2D determination: DLT, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary safety and antitumor activity data
[Phase 1] Overall safety profile
Rate and severity of adverse events
[Phase 2] Overall response rate (ORR)
ORR - the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1

Secondary Outcome Measures

[Phase 1] Overall response rate (ORR)
ORR - the proportion of patients who experience a best response of confirmed complete response (CR) or partial response (PR) according to RECIST 1.1
[Phase 1 and Phase 2] Duration of response (DOR)
DOR - time from first documented response of CR or PR to the date of first documented progressive disease or death due to any cause, whichever occurs first
[Phase 1 and Phase 2] To characterize the PK profile of BLU-701
maximum plasma drug concentration (Cmax) time to maximum plasma drug concentration (Tmax) time of last quantifiable plasma drug concentration (Tlast) area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-24 for QD and AUC0-12 for BID) trough concentration (Ctrough) apparent volume of distribution (Vz/F) terminal elimination half-life (t½) apparent oral clearance(CL/F) accumulation ratio (R)
[Phase 1] To assess treatment-induced modulation of EGFR pathway biomarkers for BLU-701 monotherapy
dual specificity phosphatase (DUSP6) sprouty RTK signaling antagonist 4 (SPRY4)
[Phase 2] Overall safety profile
Rate and severity of adverse events
[Phase 2]Disease Control Rate (DCR)
DCR - proportion of patients who experience a best response of CR, PR, or SD according to RECIST 1.1
[Phase 2] Clinical Benefit Rate (CBR)
CBR - proportion of patients who experience a confirmed CR or PR, or SD with a duration of at least 16 weeks according to RECIST 1.1
[Phase 2] Progression Free Survival (PFS)
PFS - time from the first dose of BLU-701 until the date of first documented PD or death due to any cause
[Phase 2] Overall Survival (OS)
OS - time from the first dose of BLU-701 until the date of death due to any cause
[Phase 2] Central Nervous System Overall Response Rate (CNS-ORR)
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
[Phase 2] Central Nervous System Duration of Response (CNS-DOR)
CNS-DOR - time from first documented intracranial CR or PR to the date of first documented intracranial PD
[Phase 2] Central Nervous System Progression Rate
CNS progression rate - proportion of patients with CNS progression as a component of first disease progression on study
[Phase 2] To assess the effect of BLU-701 on cardiovascular intervals, including QT, and rhythm
ECG parameters extracted from continuous 12-lead Holter recordings

Full Information

First Posted
November 30, 2021
Last Updated
June 15, 2023
Sponsor
Blueprint Medicines Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT05153408
Brief Title
(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC
Official Title
A Phase 1/2 Study of the Highly Selective EGFR Inhibitor, BLU-701, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Lack of efficacy
Study Start Date
January 13, 2022 (Actual)
Primary Completion Date
December 9, 2022 (Actual)
Study Completion Date
December 9, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Blueprint Medicines Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase 1/2, open-label, first-in-human (FIH) study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of BLU-701 as monotherapy or in combination with either osimertinib or platinum-based chemotherapy in patients with EGFRm NSCLC.
Detailed Description
The study was planned to include an initial Phase 1 portion to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BLU-701 as monotherapy (Part 1A; initially in a once daily (QD) regimen with the option to evaluate twice daily (BID) dosing if supported by emerging PK and safety data), as well as additional dose-escalation portions to determine the RP2D of BLU-701 in combination with osimertinib (Part 1B) or in combination with carboplatin and pemetrexed (Part 1C). A Phase 2 part was planned to further evaluate the efficacy and safety of BLU-701 as monotherapy at RP2D (Part 2A). Phase 1 Part 1 A was initiated; however, the study was terminated prior to establishing BLU-701 MTD and/or RP2D.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Neoplasm, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms, Neoplasms, Neoplasms by Site, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Adenocarcinoma, Carcinoma, Neoplasms by Histologic Type, Neoplasms, Nerve Tissue, EGFR C797S, EGFR C797A, EGFR L858R, EGFR Exon 19 Deletion, EGFR Gene Mutation, EGF-R Positive Non-Small Cell Lung Cancer, EGFR Mutation Resulting in Tyrosine Kinase Inhibitor Resistance, EGFR Activating Mutation, Thoracic Neoplasms, Antineoplastic Agents, Protein Kinase Inhibitors, EGFR C797G, EGFR C797X, Non Small Cell Lung Cancer
Keywords
Targeted therapy, EGFR, NSCLC, non-small cell lung cancer, EGFR mutant NSCLC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1A: BLU-701 as monotherapy
Arm Type
Experimental
Arm Description
Phase 1 dose escalation of BLU-701 as monotherapy at various dose levels
Arm Title
Part 1B: BLU-701 with osimertinib
Arm Type
Experimental
Arm Description
BLU-701 in combination with osimertinib 40 mg or 80 mg tablets for oral administration
Arm Title
Part 1C: BLU-701 with platinum-based chemotherapy
Arm Type
Experimental
Arm Description
BLU-701 in combination with platinum-based chemotherapy (carboplatin and pemetrexed): Carboplatin - IV infusion dosed to target AUC of 5-6 mg/mL min q3w Pemetrexed - IV infusion dosed to 500 mg/m2 q3w
Arm Title
Part 2A: BLU-701 as monotherapy
Arm Type
Experimental
Arm Description
Phase 2 expansion group for BLU-701 as monotherapy at a dose determined during Part 1A in patients harboring the EGFR C797X resistance mutation
Intervention Type
Drug
Intervention Name(s)
BLU-701
Intervention Description
BLU-701 for oral administration
Intervention Type
Drug
Intervention Name(s)
osimertinib
Other Intervention Name(s)
Tagrisso
Intervention Description
Osimertinib tablets for oral administration
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
IV infusion of carboplatin
Intervention Type
Drug
Intervention Name(s)
pemetrexed
Intervention Description
IV infusion of pemetrexed
Primary Outcome Measure Information:
Title
[Phase 1] Determine the maximum tolerated dose (MTD) of BLU-701 monotherapy, BLU-701 in combination with osimertinib, and BLU-701 in combination with platinum-based chemotherapy
Description
MTD determination: dose limiting toxicity (DLT) rate
Time Frame
Up to 12 months
Title
[Phase 1] Determine the recommended Phase 2 dose (RP2D) of BLU-701 monotherapy, BLU-701 in combination with osimertinib, and BLU-701 in combination with platinum-based chemotherapy
Description
RP2D determination: DLT, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary safety and antitumor activity data
Time Frame
Up to 12 months
Title
[Phase 1] Overall safety profile
Description
Rate and severity of adverse events
Time Frame
Up to 12 months
Title
[Phase 2] Overall response rate (ORR)
Description
ORR - the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1
Time Frame
Up to 30 months
Secondary Outcome Measure Information:
Title
[Phase 1] Overall response rate (ORR)
Description
ORR - the proportion of patients who experience a best response of confirmed complete response (CR) or partial response (PR) according to RECIST 1.1
Time Frame
Up to 12 months
Title
[Phase 1 and Phase 2] Duration of response (DOR)
Description
DOR - time from first documented response of CR or PR to the date of first documented progressive disease or death due to any cause, whichever occurs first
Time Frame
Up to 42 months
Title
[Phase 1 and Phase 2] To characterize the PK profile of BLU-701
Description
maximum plasma drug concentration (Cmax) time to maximum plasma drug concentration (Tmax) time of last quantifiable plasma drug concentration (Tlast) area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-24 for QD and AUC0-12 for BID) trough concentration (Ctrough) apparent volume of distribution (Vz/F) terminal elimination half-life (t½) apparent oral clearance(CL/F) accumulation ratio (R)
Time Frame
Up to 42 months
Title
[Phase 1] To assess treatment-induced modulation of EGFR pathway biomarkers for BLU-701 monotherapy
Description
dual specificity phosphatase (DUSP6) sprouty RTK signaling antagonist 4 (SPRY4)
Time Frame
Up to 42 months
Title
[Phase 2] Overall safety profile
Description
Rate and severity of adverse events
Time Frame
Up to 42 months
Title
[Phase 2]Disease Control Rate (DCR)
Description
DCR - proportion of patients who experience a best response of CR, PR, or SD according to RECIST 1.1
Time Frame
Up to 42 months
Title
[Phase 2] Clinical Benefit Rate (CBR)
Description
CBR - proportion of patients who experience a confirmed CR or PR, or SD with a duration of at least 16 weeks according to RECIST 1.1
Time Frame
Up to 42 months
Title
[Phase 2] Progression Free Survival (PFS)
Description
PFS - time from the first dose of BLU-701 until the date of first documented PD or death due to any cause
Time Frame
Up to 42 months
Title
[Phase 2] Overall Survival (OS)
Description
OS - time from the first dose of BLU-701 until the date of death due to any cause
Time Frame
Up to 42 months
Title
[Phase 2] Central Nervous System Overall Response Rate (CNS-ORR)
Description
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
Time Frame
Up to 42 months
Title
[Phase 2] Central Nervous System Duration of Response (CNS-DOR)
Description
CNS-DOR - time from first documented intracranial CR or PR to the date of first documented intracranial PD
Time Frame
Up to 42 months
Title
[Phase 2] Central Nervous System Progression Rate
Description
CNS progression rate - proportion of patients with CNS progression as a component of first disease progression on study
Time Frame
Up to 42 months
Title
[Phase 2] To assess the effect of BLU-701 on cardiovascular intervals, including QT, and rhythm
Description
ECG parameters extracted from continuous 12-lead Holter recordings
Time Frame
Up to 42 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥18 years of age at the time of signing the informed consent. Pathologically confirmed metastatic NSCLC. Tumor mutation profile determined locally via next generation sequencing (NGS), using tumor tissue (preferably 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, samples used for analysis must be obtained during or after disease progression on the last EGFR-targeted TKI received. All Parts: activating EGFR mutation (Ex19Del or L858R) Part 2A: Tumor must additionally harbor an EGFR C797X resistance mutation. Previously received: Part 1A and 2A: At least 1 prior third-generation EGFR-targeted TKI, such as osimertinib Part 1B: Patients must have experienced progressive disease while on osimertinib, were able to tolerate prior osimertinib 80 mg QD dose, and continuing on osimertinib is deemed to be in the patient's best interests in the opinion of the Investigator. Patients who have discontinued osimertinib may be eligible, if no more than 6 weeks elapse between the discontinuation of prior osimertinib and resumption of osimertinib on study. Part 1C: At least 1 prior EGFR-targeted TKI Willing to provide pretreatment tumor sample (either an archival sample or a sample obtained by pretreatment biopsy. For Phase 1, it is preferable that pretreatment tumor sample be obtained from a progressing lesion and during or after disease progression on the last EGFR-targeted TKI received. For Phase 2, pretreatment tumor sample must be obtained during or after disease progression on the last EGFR-targeted TKI treatment 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 approved for enrollment on a case-by-case basis. Part 2A: at least 1 measurable target lesion per RECIST 1.1 as assessed by the Investigator Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Agrees to use contraception consistent with local regulations Exclusion Criteria: Have disease that is suitable for local therapy administered with curative intent. Have tumor that harbors EGFR T790M mutation or any additional known driver alterations (including but not limited to, EGFR exon 20 insertions, or pathologic abnormalities of KRAS, BRAF V600E, NTRK1/2/3, HER2, ALK, ROS1, MET, or RET). Have NSCLC with mixed cell histology or a tumor with known histologic transformation (NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition). Have received the following anticancer therapy: Any third-generation EGFR TKI (such as osimertinib) within 7 days prior to the planned first dose of study drug. Note: patients in Part 1B do not require a wash-out period for osimertinib. Part 2A: Previous therapy with first- or second-generation EGFR TKI, such as erlotinib, gefitinib, afatinib or dacomitinib. Part 1C: Prior platinum-based chemotherapy for advanced or metastatic disease. Any immunotherapy or other antibody therapy (including EGFR-targeted antibodies or bi-specific antibodies) within 21 days prior to the first dose of study drug. 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-701 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. 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. 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. Have 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. Have any of the following laboratory abnormalities on last laboratory assessment prior to initiation of study drug (i.e., C1D1 or Screening): Absolute neutrophil count (ANC) <1.0×109/L (for patients in Part 1C: <1.5×109/L) Platelet count <75×109/L (for patients in Part 1C: <100×109/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) >2.5× 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, Appendix 1) or measured creatinine clearance <60 mL/min. International normalized ratio (INR) >2.3 or prothrombin time (PT) >6 seconds above ULN 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. Have known intracranial hemorrhage and/or bleeding diatheses. Have 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. Grade 1 asymptomatic ILD is not exclusionary. Have 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. Have 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. Have 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 (e.g., Type II second degree heart block or third degree heart block). Have 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, patients who have another concurrent malignancy (not lung cancer) that is clinically stable and does not require tumor-directed treatment may be eligible to participate. 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. Have active, uncontrolled infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B, hepatitis C, AIDS-related illness, or COVID19 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 are not exclusionary. For Parts 1A, 1B, and 1C: have received neutrophil or platelet growth factor support within 14 days of the first dose of study drug. Require treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration. BLU-701 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. Have 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).
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
New York University (NYU) Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
NEXT Virginia
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC

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