Study of Tarloxotinib in Pts With NSCLC (EGFR Exon 20 Insertion, HER2-activating Mutations) & Other Solid Tumors With NRG1/ERBB Gene Fusions (RAIN)

• ClinicalTrials.gov Identifier: NCT03805841
• Recruitment Status: Terminated
• First Posted: January 16, 2019
• Last Update Posted: November 19, 2021
• Sponsor: Rain Oncology Inc
• Information provided by (Responsible Party): Rain Oncology Inc

Tracking Information

• First Submitted Date: January 11, 2019
• First Posted Date: January 16, 2019
• Last Update Posted Date: November 19, 2021
• Actual Study Start Date: March 13, 2019
• Actual Primary Completion Date: April 9, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2019)

ORR [ Time Frame: through study completion, an average of 10 months ]

Objective Response Rate (number of subjects with PR or CR)

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Brief Summary: Open-label, Phase 2, single treatment arm, 3 cohorts
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• NSCLC, Stage IV
• NSCLC Stage IIIB
• NSCLC, Stage IIIC
• NSCLC, Recurrent
• EGFR Exon 20 Insertion Mutation
• HER2-activating Mutation
• ERBB Fusion
• NRG1 Fusion

Intervention

Drug: tarloxotinib bromide

weekly intravenous infusion

Other Names:

• Tarlox
• tarloxotinib

Study Arms

Experimental: Active

tarloxotinib bromide

Intervention: Drug: tarloxotinib bromide

• Publications *: 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 11, 2021): 41
• Original Estimated Enrollment (submitted: January 14, 2019): 40
• Actual Study Completion Date: April 23, 2021
• Actual Primary Completion Date: April 9, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Hong Kong, United States
• Removed Location Countries: Singapore

Administrative Information

• NCT Number: NCT03805841
• Other Study ID Numbers: RAIN-701
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: No Plan

• Current Responsible Party: Rain Oncology Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Rain Oncology Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Stephen V Liu, MD; Georgetown University

• PRS Account: Rain Oncology Inc
• Verification Date: November 2021