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

NSCLC Stage IIIB Clinical Trial

— RAIN  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03805841
• Other study ID #: RAIN-701
• Status: Terminated
• Phase: Phase 2
• Start date: March 13, 2019
• Est. completion date: April 23, 2021

Study information

• Verified date: April 2023
• Source: Rain Oncology Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open-label, Phase 2, single treatment arm, 3 cohorts

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: April 23, 2021
• Est. primary completion date: April 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• EGFR Exon 20 Insertion Mutation
• ERBB Fusion
• HER2-activating Mutation
• NRG1 Fusion
• NSCLC Stage IIIB
• NSCLC, Recurrent
• NSCLC, Stage IIIC
• NSCLC, Stage IV

Intervention

Drug:
• tarloxotinib bromide
weekly intravenous infusion

Locations

Country	Name	City	State
Canada	RAIN-701 Study Site	Toronto	Ontario
Hong Kong	RAIN-701 Study Site	Hong Kong
Hong Kong	Hong Kong United Oncology Center	Kowloon
United States	RAIN-701 Study Site	Aurora	Colorado
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	RAIN-701 Study Site	Irvine	California
United States	Pacific Shores Medical Group	Long Beach	California
United States	Comprehensive Care and Research Center, Atlanta	Newnan	Georgia
United States	RAIN-701 Study Site	Pittsburgh	Pennsylvania
United States	Providence Cancer Institute	Portland	Oregon
United States	University of California San Francisco, Helen Diller Cancer Center	San Francisco	California
United States	RAIN-701 Study Site	Seattle	Washington
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Rain Oncology Inc

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	The primary objective of this study is to evaluate the objective response rate (ORR) of tarloxotinib according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for tumors assessed by CT or MRI: Complete Response (CR) - Disappearance of all target lesions and reduction in the short axis measurement of all pathologic lymph nodes to =10 mm. Partial Response (PR) - =30% decrease in the sum of the longest diameter of the target lesions compared with baseline.; The overall response rate in each cohort will be estimated as the number of subjects with a confirmed objective response (CR or PR) divided by the number of enrolled subjects in each respective cohort.	Through study completion, an average of 10 months.