Ensartinib (X-396) for Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive by an FDA-approved assay, performed centrally. Patients must be ALK positive by local test prior to submitting tissue to the central lab. Randomization will occur after ALK positive confirmation is received from the central lab. Patients may have received up to 1 prior chemotherapy regimen for metastatic disease, which may also include maintenance therapy. Note that patients that have received adjuvant or neoadjuvant chemotherapy and developed metastatic disease within 6 months from the end of that therapy would be considered to have received 1 prior regimen for metastatic disease\n- Patients must have measurable disease per RECIST v. 1.1.\n- Willingness and ability to comply with the trial and follow-up procedures.\n- Ability to understand the nature of this trial and give written informed consent. Note the following pertains to patients enrolled in France\n- Specific to France: Subjects will be eligible for inclusion in this study only affiliated to the French Social Security system, and currently benefit from the corresponding rights and cover.\n- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2. (see Appendix A)\n- Life expectancy of at least 12 weeks.\n- Ability to swallow and retain oral medication.\n- Adequate organ system function, defined as follows: a. Absolute neutrophil count (ANC) ≥1.5 x 109/L b. Platelets ≥100 x 109/L c. Hemoglobin ≥9 g/dL (≥90 g/L). Note that transfusions are allowed to meet the required hemoglobin level d. Total bilirubin ≤1.5 times the upper limit of normal (ULN) e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN if no liver involvement or ≤5 x ULN with liver involvement. f. Creatinine ≤1.5 x ULN. If >1.5 x ULN, patient may still be eligible if calculated creatinine clearance ³50 mL/min (0.83 mL/s) as calculated by the Cockcroft-Gault method.\n- Brain metastases allowed if asymptomatic at study baseline. Patients with untreated brain metastases must not be on corticosteroids. If patients have neurological symptoms or signs due to CNS metastases, patients need to complete whole brain radiation or focal treatment at least 14 days before start of study treatment and be asymptomatic on stable or decreasing doses of corticosteroids at baseline.\n- Men with partners of childbearing potential willing to use adequate contraceptive measures during the study and for 90 days after the last dose of study medication.\n- Women who are not of child-bearing potential, and women of child-bearing potential who agree to use adequate contraceptive measures during the study and for 90 days after the last dose of study medication, and who have a negative serum or urine pregnancy test within 1 week prior to initial trial treatment.\n- Patients must be ≥18 years of age."}

Exclusion criteria

• {"criterion_text":"- Patients that have previously received an ALK TKI or PD-1/PD-L1 therapy, and patients currently receiving cancer therapy (i.e., other targeted therapies, chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization).\n- Patients at risk for GI perforation.\n- Clinically significant cardiovascular disease including: QTcF interval >450 ms for men and >470 ms for women, symptomatic bradycardia <45 beats per minute or other significant ECG abnormalities in the investigator’s opinion. Clinically uncontrolled hypertension in the investigator’s opinion (e.g., blood pressure >160/100 mmHg; note that isolated elevated readings considered to not be indicative of uncontrolled hypertension are allowed). The following within 6 months prior to Cycle 1 Day 1: Congestive heart failure (New York Heart Class III or IV (see Appendix D). Arrhythmia or conduction abnormality requiring medication. Note: patients with atrial fibrillation/flutter controlled by medication and arrhythmias controlled by pacemakers are eligible. Severe/unstable angina, coronary artery/peripheral bypass graft, or myocardial infarction. Cerebrovascular accident or transient ischemia.\n- Patients who are immunosuppressed (including known HIV infection), have a serious active infection at the time of treatment, have interstitial lung disease/pneumonitis, or have any serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. Patients with controlled hepatitis C, in the investigator’s opinion, are allowed. Patients with known hepatitis B must be HBeAg and HB viral DNA negative for enrollment. Note that, because of the high prevalence, all patients in the Asia-Pacific region (except Australia, New Zealand, and Japan) must be tested and, if HBsAg positive, must be HBeAg and HB viral DNA negative for enrollment.\n- Known hypersensitivity to tartrazine, a dye used in the ensartinib 100 mg capsule.\n- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.\n- Concurrent condition that in the investigator’s opinion would jeopardize compliance with the protocol or would impart excessive risk associated with study participation that would make it inappropriate for the patient to be enrolled.\n- Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol. Note the following pertains to patients enrolled in France.\n- Specific to France: Subjects will not be eligible when under legal protection.\n- Use of an investigational drug within 21 days prior to the first dose of study drug. Note that to be eligible, any drug-related toxicity should have recovered to Grade 1 or less, with the exception of alopecia.\n- Any chemotherapy within 4 weeks, or major surgery or radiotherapy within the last 14 days.\n- Patients with primary CNS tumors and leptomeningeal disease are ineligible.\n- Patients with a previous malignancy within the past 3 years (other than curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, or any cancer that is considered to be cured and have no impact on PFS and OS for the current NSCLC).\n- Concomitant systemic use of anticancer herbal medications. These should be stopped prior to study entry.\n- Patients receiving: a. Strong CYP3A inhibitors (including, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit, grapefruit juice) b. Strong CYP3A inducers (including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's Wort) c. CYP3A substrates with narrow therapeutic window (including, but not limited to, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus).\n- Women who are pregnant or breastfeeding.\n- Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of study medications."}

Primary endpoints

• {"endpoint_text":"- Progression-free survival (PFS) as assessed by independent radiology review (IRR) based on RECIST v. 1.1 criteria.","definition_or_measurement_approach":"Assessed by independent radiology review (IRR) using RECIST v.1.1 criteria."}

Secondary endpoints

• {"endpoint_text":"- Key Secondary Efficacy Endpoints: Overall survival, CNS response rate (based on IRR), time to CNS progression (based on IRR), objective response rate (based on IRR)","definition_or_measurement_approach":"Overall survival; CNS response rate, time to CNS progression, objective response rate assessed based on independent radiology review (IRR) as specified."}
• {"endpoint_text":"- PFS (based on investigator assessment)","definition_or_measurement_approach":"Progression-free survival assessed by investigator."}
• {"endpoint_text":"- ORR (based on investigator assessment)","definition_or_measurement_approach":"Objective response rate assessed by investigator."}
• {"endpoint_text":"- Time to response (based on investigator assessment and IRR)","definition_or_measurement_approach":"Time from randomization to first documented response assessed by investigator and independent radiology review (IRR)."}
• {"endpoint_text":"- Duration of response (based on investigator assessment and IRR)","definition_or_measurement_approach":"Time from first documented response to disease progression or death, assessed by investigator and IRR."}
• {"endpoint_text":"- CNS response rate (based on investigator assessment)","definition_or_measurement_approach":"Central nervous system response rate as assessed by investigator."}
• {"endpoint_text":"- Time to CNS progression (based on investigator assessment)","definition_or_measurement_approach":"Time to central nervous system progression assessed by investigator."}
• {"endpoint_text":"- Patient reported time to deterioration (TTD) as measured by the EORTC C30/LC13 QoL questionnaire and Lung Cancer Symptom Scale (LCSS)","definition_or_measurement_approach":"Patient-reported time to deterioration measured using EORTC QLQ-C30/LC13 and LCSS instruments."}
• {"endpoint_text":"- Patient reported health-related quality of life (HRQoL) as measured by the EORTC C30/LC13 QoL questionnaire and LCSS.","definition_or_measurement_approach":"Health-related quality of life measured using EORTC QLQ-C30/LC13 and LCSS instruments."}
• {"endpoint_text":"- Pharmacodynamic (PD) and possible pharmacogenetic (PG) assessments and biomarkers in blood or/and tissue sample. Biomarkers in the blood or tissue related to efficacy.","definition_or_measurement_approach":"PD and possible PG assessments and exploratory biomarkers measured in blood and/or tissue; biomarkers related to efficacy will be assessed per protocol."}

Belgium

Earliest CTIS Part Ii Submission Date

25-10-2024

Latest Decision Or Authorization Date

07-11-2024

Processing Time Days

13

Number Of Sites

1

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

25-10-2024

Latest Decision Or Authorization Date

31-12-2024

Processing Time Days

67

Number Of Sites

4

Number Of Participants

9

Italy

Earliest CTIS Part Ii Submission Date

25-10-2024

Latest Decision Or Authorization Date

18-11-2024

Processing Time Days

24

Number Of Sites

3

Number Of Participants

18

Spain

Earliest CTIS Part Ii Submission Date

25-10-2024

Latest Decision Or Authorization Date

06-11-2024

Processing Time Days

12

Number Of Sites

2

Number Of Participants

7

Netherlands

Earliest CTIS Part Ii Submission Date

25-10-2024

Latest Decision Or Authorization Date

06-11-2024

Processing Time Days

12

Number Of Sites

2

Number Of Participants

3

Poland

Earliest CTIS Part Ii Submission Date

25-10-2024

Latest Decision Or Authorization Date

11-11-2024

Processing Time Days

17

Number Of Sites

2

Number Of Participants

3

Czechia

Earliest CTIS Part Ii Submission Date

25-10-2024

Latest Decision Or Authorization Date

11-11-2024

Processing Time Days

17

Number Of Sites

2

Number Of Participants

5

Primary sponsor

Full Name

Xcovery Holding Co. LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Iqvia Biotech LLC

Name

Iqvia Biotech Limited

Name

Almac Clinical Services (Ireland) Limited

Responsibilities

QP Release/ Depot Distribution in EU

Name

Almac Clinical Services Limited

Responsibilities

QP Release/ Depot Distribution in EU

Name

Medidata Solutions Inc.

Third parties

• {"country":"United Kingdom","full_name":"Catalent U.K. Packaging Limited","duties_or_roles":"Packaging/Manufacturing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Biotech LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"QP Release/ Depot Distribution in EU","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"QP Release/ Depot Distribution in EU","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q2 Solutions","duties_or_roles":"Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Clinical microbiology, Histopathology, Serology/ endocrinology, PK, PD, ALK Testing and companion diagnostics","organisation_type":"SME"}
• {"country":"United States","full_name":"ERT (Clario)","duties_or_roles":"ECG Analysis / review","organisation_type":"Industry"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}