Expanded Access to Ensartinib for Participants With ALK+ NSCLC

Expanded Access Intermediate-Size Patient Population Protocol

This is an open-label, multicenter, intermediate-sized expanded access treatment protocol to the existing IND 111,695 for ensartinib (X-396). The treatment plan is designed to provide ensartinib to participants with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC).

Study Overview

• Status: Available
• Conditions: Non-Small Cell Lung Cancer; ALK Gene Rearrangement Positive
• Intervention / Treatment: Drug: Ensartinib

Detailed Description

Open-label, multi-center, intermediate-sized expanded access treatment protocol for X396-CLI-101 (Phase I/II, First-in-Human, Dose-Escalation Study of X-396 in Patients with Advanced Solid Tumors and Expansion Phase in Patients with ALK+ Non-Small Cell Lung Cancer)

• Study Type: Expanded Access
• Expanded Access Type: Intermediate-size Population

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Available
      • Stanford University
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Available
      • Walter Reed National Military Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37240
      • Available
      • Vanderbilt University
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Available
      • University of Wisconsin Carbone Cancer Ctr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adult patients (>18 years-of-age) with advanced ALK-positive NSCLC as determined by an FDA approved test.
2. Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1.
3. Informed consent must be provided by each patient.
4. Patient is not eligible or does not have access for participation in any of the other ongoing clinical trials for ensartinib.
5. Ability to swallow and retain oral medication.
6. Male and female patients must agree to abstain or to use two highly effective forms of contraception during the treatment period and for 90 days after the last dose of study medication.
7. Adequate organ system function.
8. Patients with treated CNS metastases are eligible if they are asymptomatic with respect to the CNS metastases and do not require escalating doses of systemic corticosteroids. ALK-positive patients with untreated CNS lesions may be allowed to enroll as long as the patients are asymptomatic with respect to the CNS metastases and do not require systemic corticosteroids or anticonvulsants.

Exclusion Criteria:

1. Patients currently receiving cancer therapy.
2. Use of an investigational or targeted drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of ensartinib. A minimum of 10 days between termination of the treatment and administration of ensartinib is required. However, in the case of ALK TKIs, a 2-day window between termination of the TKI and the start of ensartinib is allowed. In addition, any drug-related toxicity should have recovered to Grade 1 or less, with the exception of alopecia.
3. Any major surgery or immunotherapy within the last 21 days (focal radiation does not require a washout period; ≥4 weeks for whole brain radiotherapy). Chemotherapy regimens with delayed toxicity within the last 4 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks.
4. Patients with a known allergy or delayed hypersensitivity reaction to drugs chemically related to ensartinib (e.g., crizotinib) or to the active ingredient of ensartinib or to tartrazine, a dye used in the ensartinib 100 mg capsules.
5. Patients receiving CYP3A substrates with narrow therapeutic indices, strong CYP3A inhibitors, and strong CYP3A inducers.
6. Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of ensartinib.
7. Clinically significant cardiovascular disease.
8. Patients who are immunosuppressed (including known HIV infection), have a serious active infection at the time of treatment, have known hepatitis C, or have any serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
9. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
10. Have a history or the presence at baseline of pulmonary interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis.
11. Females who are pregnant or breastfeeding.
12. Patient with any concurrent condition or receiving any concurrent medication that, in the investigator's opinion, would impart excessive risk associated with study participation or otherwise make it inappropriate for the patient to participate.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: Xcovery Holding Company, LLC

Publications and helpful links

General Publications

• Lovly CM, Heuckmann JM, de Stanchina E, Chen H, Thomas RK, Liang C, Pao W. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31. doi: 10.1158/0008-5472.CAN-10-3879. Epub 2011 May 25.
• Horn L, Infante JR, Reckamp KL, Blumenschein GR, Leal TA, Waqar SN, Gitlitz BJ, Sanborn RE, Whisenant JG, Du L, Neal JW, Gockerman JP, Dukart G, Harrow K, Liang C, Gibbons JJ, Holzhausen A, Lovly CM, Wakelee HA. Ensartinib (X-396) in ALK-Positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study. Clin Cancer Res. 2018 Jun 15;24(12):2771-2779. doi: 10.1158/1078-0432.CCR-17-2398. Epub 2018 Mar 21.

Study record dates

Study Major Dates

• Study Start: December 7, 2022
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: October 28, 2019
• First Submitted That Met QC Criteria: October 28, 2019
• First Posted (Actual): October 31, 2019

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: carcinoma; NSCLC; Non-Small Cell Lung Cancer; ALK positive; ensartinib; X-396; X396; anaplastic lymphoma kinase; ALK+; ALK inhibitor
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Ensartinib
• Other Study ID Numbers: X396-CLI-205

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No