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

Phase 2

Terminated

• Conditions: EGFR Exon 20 Insertion Mutation; HER2-activating Mutation; ERBB Fusion; NSCLC Stage IIIB; NRG1 Fusion; NSCLC, Stage IV; NSCLC, Stage IIIC; NSCLC, Recurrent
• Interventions: Drug: tarloxotinib bromide

• Registration Number: NCT03805841
• Lead Sponsor: Rain Oncology Inc

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-11
• Study First Submitted QC: 2019-01-14
• Study First Posted: 2019-01-16
• Study Start: 2019-03-13
• Primary Completion: 2021-04-09
• Study Completion: 2021-04-23
• Results First Submitted: 2023-03-28
• Status Verified: 2023-04
• Results First Submitted QC: 2023-06-27
• Last Update Submitted: 2023-06-27
• Results First Posted: 2023-06-28
• Last Update Posted: 2023-06-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 41

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Active	tarloxotinib bromide	tarloxotinib bromide

Primary Outcome Measures

Name	Time	Method
ORR	Through study completion, an average of 10 months.	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.

Trial Locations

Locations (9)

Pacific Shores Medical Group; 🇺🇸 Long Beach, California, United States

Providence Cancer Institute; 🇺🇸 Portland, Oregon, United States

University of California San Francisco, Helen Diller Cancer Center; 🇺🇸 San Francisco, California, United States

Georgetown University Medical Center; 🇺🇸 Washington, District of Columbia, United States

Northwestern University Feinberg School of Medicine; 🇺🇸 Chicago, Illinois, United States

Comprehensive Care and Research Center, Atlanta; 🇺🇸 Newnan, Georgia, United States

Henry Ford Cancer Institute; 🇺🇸 Detroit, Michigan, United States

RAIN-701 Study Site; 🇭🇰 Hong Kong, Hong Kong

Hong Kong United Oncology Center; 🇭🇰 Kowloon, Hong Kong