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

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

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C1
      • RAIN-701 Study Site
• Hong Kong
  • Hong Kong, Hong Kong
    • RAIN-701 Study Site
  • Kowloon, Hong Kong
    • Hong Kong United Oncology Center
• United States
  • California
    • Irvine, California, United States, 92697
      • RAIN-701 Study Site
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
    • San Francisco, California, United States, 94158
      • University of California San Francisco, Helen Diller Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • RAIN-701 Study Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Comprehensive Care and Research Center, Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • RAIN-701 Study Site
  • Washington
    • Seattle, Washington, United States, 98109
      • RAIN-701 Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; tarloxotinib bromide	Drug: tarloxotinib bromide; weekly intravenous infusion; Other Names: Tarlox; tarloxotinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: Rain Oncology Inc
• Investigators: Principal Investigator: Stephen V Liu, MD, Georgetown University

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2019
• Primary Completion (Actual): April 9, 2021
• Study Completion (Actual): April 23, 2021

Study Registration Dates

• First Submitted: January 11, 2019
• First Submitted That Met QC Criteria: January 14, 2019
• First Posted (Actual): January 16, 2019

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Anticonvulsants; Bromides
• Other Study ID Numbers: RAIN-701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No Plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No