Clinical trial NCT03805841: Study of Tarloxotinib in Pts With NSCLC (EGFR Exon 20 Insertion, HER2-activating Mutations) & Other Solid Tumors With NRG1/ERBB Gene Fusions
Official title: Phase 2 Study - Evaluate the Clinical Activity of Tarloxotinib in Patients With Non-Small Cell Lung Cancer That Harbors an EGFR Exon 20 Insertion or HER2-Activating Mutation and Other Advanced Solid Tumors With NRG1/ERBB Family Gene Fusions
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: NSCLC, Stage IV
NSCLC Stage IIIB
NSCLC, Stage IIIC
NSCLC, Recurrent
EGFR Exon 20 Insertion Mutation
HER2-activating Mutation
ERBB Fusion
NRG1 Fusion
Lead sponsor: Rain Oncology Inc
Sponsor class: INDUSTRY
First posted: 2019-01-16
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Open-label, Phase 2, single treatment arm, 3 cohorts


Eligibility criteria: Key Inclusion Criteria:

* Histologically and/or cytologically confirmed primary diagnosis of NSCLC, Stage IV, Stage IIIB or IIIC not amenable to definitive curative intent therapy, or recurrent disease after prior diagnosis of Stage I-III disease. Cohort C locally advanced or metastatic solid tumor.
* Progression of disease on or after a platinum-based chemotherapy regimen (Cohorts A and B) or after standard of care (Cohort C)
* EGFR exon 20 insertion mutation (Cohort A) or HER2 activating mutation (Cohort B) or NRG1 or ERBB family gene fusions (Cohort C)
* Measurable disease according to RECIST v.1.1
* ECOG performance status of 0 or 1
* Serum creatinine ≤ 1.5 x ULN (or calculated creatinine clearance ≥ 60 mL/min using Cockcroft Gault equation)
* Total bilirubin: ≤ 1.5 x ULN or ≤ 3 x ULN in the presence of liver metastases
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, or ≤ 5 x ULN, in the presence of liver metastases
* Absolute neutrophil count (ANC) ≥ 1,500 cells/μL
* Hemoglobin ≥ 9 g/dL or 5.6 mmol/L
* Platelet count ≥ 100,000/μL
* No evidence of second or third degree atrioventricular block
* No clinically significant arrhythmia (i.e.; pauses of \> 4 seconds, VT of any duration, SVT \> 4 beats/minute)
* QRS interval ≤ 110 ms
* QTcF interval of \< 450 ms
* PR interval ≤ 200 ms
* Adequate pretreatment tumor sample (125 µm of FFPE block or at least 8 prepared slides)

Key Exclusion Criteria:

* Another known activating oncogene driver mutation
* (Cohorts A and B Only) Previously received anti EGFR or anti HER2 tyrosine kinase inhibitors
* (Cohorts A and B Only) Previously received anti EGFR or anti HER2 monoclonal antibodies or EGFR or HER2 antibody drug conjugates
* Investigational therapy administered within the 28 days or 5 half lives
* Chemotherapy or radiation within 14 days prior to Cycle 1 Day 1
* Immunotherapy within 21 days
* Clinically active or symptomatic interstitial lung disease (ILD) or interstitial pneumonitis, or a history of clinically significant ILD or radiation pneumonitis
* Untreated and/or symptomatic CNS malignancies (primary or metastatic);
* Receiving medication that prolongs QT interval, with a risk of causing Torsade de Pointes (TdP)
* Personal or familial history of Long QT Syndrome
* NYHA class III or IV or LVEF \< 55%
* Myocardial infarction, severe or unstable angina within 6 months
* History of TdP, ventricular arrhythmia
* Significant thrombotic or embolic events within 3 months
* Uncontrolled or severe cardiovascular disease
* Concurrent malignancy expected to require treatment within 2 years or interfere with study outcomes
* History of severe allergic reactions or hypersensitivity to compounds of similar chemical or biologic composition as tarloxotinib
* Known HIV infection or active Hepatitis B or C

Primary outcomes:
measure: ORR
timeFrame: Through study completion, an average of 10 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Irvine
country: United States
facility: RAIN-701 Study Site
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: San Francisco
country: United States
facility: University of California San Francisco, Helen Diller Cancer Center
state: California
city: Aurora
country: United States
facility: RAIN-701 Study Site
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Newnan
country: United States
facility: Comprehensive Care and Research Center, Atlanta
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Pittsburgh
country: United States
facility: RAIN-701 Study Site
state: Pennsylvania
city: Seattle
country: United States
facility: RAIN-701 Study Site
state: Washington
city: Toronto
country: Canada
facility: RAIN-701 Study Site
state: Ontario
city: Hong Kong
country: Hong Kong
facility: RAIN-701 Study Site
city: Kowloon
country: Hong Kong
facility: Hong Kong United Oncology Center
Study officials:
affiliation: Georgetown University
name: Stephen V Liu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ye L, Chen X, Zhou F. EGFR-mutant NSCLC: emerging novel drugs. Curr Opin Oncol. 2021 Jan;33(1):87-94. doi: 10.1097/CCO.0000000000000701.