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).

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)

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.