Authorised Therapeutic confirmatory (Phase III) Advanced ALK positive non-small cell lung cancer

Study with investigational drug PF-06463922 and comparator crizotinib in patients with a specific type of advanced lung cancer

EU CTIS ID: 2023-509169-19-00

What this study is testing

To demonstrate that lorlatinib as a single agent (Arm A) is superior to crizotinib alone (Arm B) in prolonging Progression Free Survival (PFS) in advanced ALK positive NSCLC participants who are treatment naïve.

Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Diagnosis: a. Study Population: Participants with histologically or cytologically confirmed diagnosis of locally advanced [(Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) by American Joint Committee on Cancer (AJCC) v 7.0] ALK positive NSCLC where ALK status is determined by the FDA approved (for use in US), CE (Conformité Européene) marked (for EU and other countries that accept CE marking), and PMDA(Pharmaceuticals and Medical Devices Agency) approved (for use in Japan) Ventana ALK (D5F3) Companion Diagnostic (CDx) IHC test performed on the Ventana ULTRA or XT platforms (refer to Section 6.1.1.1 for any prescreening activity related to ALK determination); b. Tumor Requirements: At least 1 extracranial measurable target lesion per RECIST v. 1.1 that has not been previously irradiated. CNS metastases are allowed if asymptomatic and: 1. Either untreated and not currently requiring corticosteroid treatment, or on a stable or decreasing dose of ≤10 mg QD prednisone or equivalent; or 2. Local treatment has been completed with full recovery from the acute effects of radiation therapy or surgery prior to randomization, and if corticosteroid treatment for these metastases has been withdrawn for at least 4 weeks with neurological stability; or 3. In case of leptomeningeal disease (LMD) or carcinomatous meningitis (CM) if visualized on magnetic resonance imaging (MRI), or if baseline CSF positive cytology is available. c. Tissue Requirements: All participants must have an archival formalin fixed, paraffin embedded (FFPE) tissue specimen available and collected prior to randomization. If archived tissue is unavailable, then a mandatory de novo biopsy must be performed.
10. Serum pregnancy test (for females of childbearing potential) negative at screening. Female participants of non childbearing potential must meet at least 1 of the following criteria: • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause (which may be confirmed with a serum follicle stimulating hormone [FSH] level confirming the postmenopausal state if appropriate); • Have undergone a documented hysterectomy and/or bilateral oophorectomy; • Have medically confirmed ovarian failure. All other female participants (including female participants with tubal ligations) are considered to be of childbearing potential.
11. Evidence of a personally signed and dated informed consent document indicating that the participant (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
12. Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
2. No prior systemic NSCLC treatment for advanced (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) disease, including molecularly targeted agents (eg, ALK TKIs), angiogenesis inhibitors, immunotherapy, or chemotherapy. Prior treatment for earlier Stages of the NSCLC only allowed if completed more than 12 months prior to randomization.
3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, or 2.

You likely can't join if

1. Spinal cord compression unless the participant has good pain control attained through therapy, and there is stabilization or recovery of neurological function for the 4 weeks prior to randomization.
10. Evidence of active malignancy (other than NSCLC, non melanoma skin cancer, or localized prostate cancer or any in situ cancer which does not currently require treatment) within the last 3 years prior to randomization.
11. Concurrent use of any of the following food or drugs (consult the sponsor if in doubt whether a food or a drug falls into any of the below categories) within 12 days prior to the first dose of lorlatinib or crizotinib. a. Known strong CYP3A inhibitors (eg, strong CYP3A inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits [eg, Seville oranges, pomelos], boceprevir, cobicistat, conivaptan, itraconazole, ketoconazole, posaconazole, ritonavir alone and with danoprevir or elvitegravir or indinavir or lopinavir or paritaprevir or ombitasvir or dasabuvir or saquinavir or tipranavir, telaprevir, troleandomycin, and voriconazole. The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed. b. Known CYP3A substrates with narrow therapeutic index, such as astemizole*, terfenadine*, cisapride*, pimozide, quinidine, tacrolimus, cyclosporine, sirolimus, alfentanil, fentanyl (including transdermal patch) or ergot alkaloids (ergotamine, dihydroergotamine) (*withdrawn from US market). c. Known strong CYP3A inducers (eg, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s Wort). d. Known P gp substrates with a narrow therapeutic index (eg, digoxin).
12. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
13. Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or participants who are Pfizer employees, including their family members, directly involved in the conduct of the study.
14. Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.

See the full eligibility criteria

Who can join

1. Diagnosis: a. Study Population: Participants with histologically or cytologically confirmed diagnosis of locally advanced [(Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) by American Joint Committee on Cancer (AJCC) v 7.0] ALK positive NSCLC where ALK status is determined by the FDA approved (for use in US), CE (Conformité Européene) marked (for EU and other countries that accept CE marking), and PMDA(Pharmaceuticals and Medical Devices Agency) approved (for use in Japan) Ventana ALK (D5F3) Companion Diagnostic (CDx) IHC test performed on the Ventana ULTRA or XT platforms (refer to Section 6.1.1.1 for any prescreening activity related to ALK determination); b. Tumor Requirements: At least 1 extracranial measurable target lesion per RECIST v. 1.1 that has not been previously irradiated. CNS metastases are allowed if asymptomatic and: 1. Either untreated and not currently requiring corticosteroid treatment, or on a stable or decreasing dose of ≤10 mg QD prednisone or equivalent; or 2. Local treatment has been completed with full recovery from the acute effects of radiation therapy or surgery prior to randomization, and if corticosteroid treatment for these metastases has been withdrawn for at least 4 weeks with neurological stability; or 3. In case of leptomeningeal disease (LMD) or carcinomatous meningitis (CM) if visualized on magnetic resonance imaging (MRI), or if baseline CSF positive cytology is available. c. Tissue Requirements: All participants must have an archival formalin fixed, paraffin embedded (FFPE) tissue specimen available and collected prior to randomization. If archived tissue is unavailable, then a mandatory de novo biopsy must be performed.
10. Serum pregnancy test (for females of childbearing potential) negative at screening. Female participants of non childbearing potential must meet at least 1 of the following criteria: • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause (which may be confirmed with a serum follicle stimulating hormone [FSH] level confirming the postmenopausal state if appropriate); • Have undergone a documented hysterectomy and/or bilateral oophorectomy; • Have medically confirmed ovarian failure. All other female participants (including female participants with tubal ligations) are considered to be of childbearing potential.
11. Evidence of a personally signed and dated informed consent document indicating that the participant (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
12. Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
2. No prior systemic NSCLC treatment for advanced (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) disease, including molecularly targeted agents (eg, ALK TKIs), angiogenesis inhibitors, immunotherapy, or chemotherapy. Prior treatment for earlier Stages of the NSCLC only allowed if completed more than 12 months prior to randomization.
3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, or 2.
4. Age ≥18 years (or ≥20 years as required by local regulation).
5. Adequate Bone Marrow Function, including: a. Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 or ≥1.5 x 109/L; b. Platelets ≥100,000/mm3 or ≥100 x 109/L; c. Hemoglobin ≥9 g/dL.
6. Adequate Pancreatic Function, including: a. Serum total amylase ≤1.5 x upper limit of normal (ULN)*; b. Serum lipase ≤1.5 x ULN. *if total amylase >1.5 x ULN, but pancreatic amylase is within the ULN, then participant may be enrolled.
7. Adequate Renal Function, including: a. Serum creatinine ≤1.5 x ULN or estimated creatinine clearance ≥60 mL/min as calculated using the method standard for the institution.
8. Adequate Liver Function, including: a. Total serum bilirubin ≤1.5 x ULN; b. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN (≤5.0 x ULN in case of liver metastases).
9. Acute effects of prior radiotherapy resolved to baseline severity or to CTCAE Grade ≤1 except for AEs that in the investigator’s judgment do not constitute a safety risk for the participant.

What rules you out

1. Spinal cord compression unless the participant has good pain control attained through therapy, and there is stabilization or recovery of neurological function for the 4 weeks prior to randomization.
10. Evidence of active malignancy (other than NSCLC, non melanoma skin cancer, or localized prostate cancer or any in situ cancer which does not currently require treatment) within the last 3 years prior to randomization.
11. Concurrent use of any of the following food or drugs (consult the sponsor if in doubt whether a food or a drug falls into any of the below categories) within 12 days prior to the first dose of lorlatinib or crizotinib. a. Known strong CYP3A inhibitors (eg, strong CYP3A inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits [eg, Seville oranges, pomelos], boceprevir, cobicistat, conivaptan, itraconazole, ketoconazole, posaconazole, ritonavir alone and with danoprevir or elvitegravir or indinavir or lopinavir or paritaprevir or ombitasvir or dasabuvir or saquinavir or tipranavir, telaprevir, troleandomycin, and voriconazole. The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed. b. Known CYP3A substrates with narrow therapeutic index, such as astemizole*, terfenadine*, cisapride*, pimozide, quinidine, tacrolimus, cyclosporine, sirolimus, alfentanil, fentanyl (including transdermal patch) or ergot alkaloids (ergotamine, dihydroergotamine) (*withdrawn from US market). c. Known strong CYP3A inducers (eg, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s Wort). d. Known P gp substrates with a narrow therapeutic index (eg, digoxin).
12. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
13. Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or participants who are Pfizer employees, including their family members, directly involved in the conduct of the study.
14. Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.
15. Pregnant female participants; breastfeeding female participants; fertile male participants and female participants of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 97 days, if male or 35 days if female, after the last dose of investigational product if under lorlatinib or 90 days if under crizotinib.
2. Major surgery within 4 weeks prior to randomization. Minor surgical procedures (eg, port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.
3. Radiation therapy within 2 weeks prior to randomization, including stereotactic or partial brain irradiation. Participants who complete whole brain irradiation within 4 weeks prior to randomization or palliative radiation therapy outside of the CNS within 48 hours prior to randomization will also not be included in the study.
4. Gastrointestinal abnormalities, including inability to take oral medication; requirement for intravenous alimentation; prior surgical procedures affecting absorption including total gastric resection or lap band; active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease; treatment for active peptic ulcer disease in the past 6 months; malabsorption syndromes.
5. Known prior or suspected severe hypersensitivity to study drugs or any component in their formulations.
6. Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV) or hepatitis C virus (HCV) (eg, in case of known HBsAg or HCV antibody positivity), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness.
7. Clinically significant vascular (both arterial and venous) and non vascular cardiac conditions, (active or within 3 months prior to enrollment), which may include, but are not limited to: • Arterial disease such as cerebral vascular accident/stroke (including Transient Ischemic Attack TIA), myocardial infarction, unstable angina; • Venous diseases such as cerebral venous thrombosis, symptomatic pulmonary embolism; • Non vascular cardiac disease such as congestive heart failure (New York Heart Association Classification Class ≥ II), second degree or third degree AV block (unless paced) or any AV block with PR >220 msec; or ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, uncontrolled atrial fibrillation of any grade, bradycardia defined as <50 bpm (unless participant is otherwise healthy such as long distance runners, etc.), machine read Electrocardiogram (ECG) with QTc >470 msec, or congenital long QT syndrome.
8. Participants with predisposing characteristics for acute pancreatitis according to investigator judgment (eg, uncontrolled hyperglycemia, current gallstone disease) in the last month prior to randomization.
9. History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis.

The study team makes the final eligibility decision.

Where it's taking place

Taiwan
Russian Federation
Australia
Korea, Republic of
India
Hong Kong
United States
Argentina
Singapore
Japan
Mexico
China
United Kingdom
Canada
Turkey

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Taiwan; Russian Federation; Australia; Korea, Republic of; India; Hong Kong and 9 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.