Comparing 4 approaches for NSCLC stage IV

Exclusion

• −Age ≥ 18 years old.
• −Participants with known history of severe hypersensitive reactions to docetaxel or to other drugs formulated with polysorbate 80.
• −History of allergic reactions to tislelizumab.
• −Known history of severe hypersensitive reactions to docetaxel or to other drugs formulated with polysorbate 80.
• −Ability to attend required study visits and return for adequate follow-upFollow-upContinued check-ins after the treatment part is finished.Read more →, as required by this protocolProtocolThe detailed plan a study must follow.Read more →.
• −Agreement to practice effective contraception for female participants of child-bearing potential and nonsterile males. Female participants of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Female participants of childbearing potential must have a negative serum pregnancy test at screeningScreeningThe checks done before joining, to see whether a study fits.Read more → and adhere to using a highly effective method of contraception (eg, tubal ligation, approved hormonal contraceptive associated with inhibition of ovulation, or an intrauterine device \[IUD\]) prior to screening and agree to continue its use during the study or be surgically sterilized (eg, hysterectomy) while on study and for 7 months post last dose of study drug. Male participants must agree to use barrier methods of birth controlControl groupThe group a new treatment is measured against.Read more → while on study and for 7 months post last dose of study drug.
• −Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks and have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study medication. Participants with asymptomatic brain metastases (ie, no neurological symptoms, no requirements for corticosteroids, and no lesion \>1.5 cm) may participate but will require regular imaging of the brain as a siteTrial siteA hospital or clinic where a study is actually run.Read more → of disease.
• −History of known active hepatitis B or C infection to be assessed within 6 months prior to enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more → using locally accepted standard of careStandard of careThe treatment normally given for a condition outside a study.Read more → measurements. (Resolved cases are allowed.)
• −Participants with known HIV infection must be receiving antiretroviral therapy and have an undetectable viral load at their most recent viral load test within 6 months prior to enrollment.
• −Have an active or uncontrolled hepatitis B and/or hepatitis C infection and are positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis B surface antigen \[HBsAg\], anti-hepatitis B surface antibody \[anti-HBs\], anti-hepatitis B core antibody \[anti-HBc\], or hepatitis B virus \[HBV\] DNA), and/or hepatitis C infection (as per hepatitis C virus \[HCV\] RNA) within 28 days of randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →. Participants are eligible if they:
• −Have received hepatitis B vaccination with only anti-HBs positivity and no clinical signs of hepatitis.
• −Have HbsAg+ with HBV infection for more than 6 months (ie, chronic HBV infection) meeting the following conditions:
• −i. HBV DNA viral load \< 2,000 IU/mL. ii. Have normal transaminase values, or, if liver metastases are present, abnormal transaminases with a result of AST/ALT \< 3 ULN that are not attributable to HBV infection.
• −c. Have been curatively treated for hepatitis.
• −Systemic autoimmune disease currently requiring treatment (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma). The participant must have been off treatment for 180 days.
• −History of any of the following: drug-induced severe cutaneous adverse reactionAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → (SCAR), including, but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), or dose-limiting immune-mediated reactions.
• −History of allogeneic hematopoietic stem cell transplant or organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring treatment with systemic steroids; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (eg, prednisone or hydrocortisone) and corticosteroids used to manage AEs are permitted.
• −Participants with AGA of ALK.
• −Active infection requiring antibiotic therapy.
• −Have known active central nervous system (CNS) metastases, carcinomatous meningitis, and/or spinal cord compression.
• −Body weight ≤ 40 kg at screening.
• −Active treatment with CYP3A4 inhibitors.
• −Received a live vaccine ≤ 4 weeks prior to the first dose of study drug(s).
• −History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• −Inadequate organ function, evidenced by the following laboratory results:
• −Absolute lymphocyte count \< institutional lower limit of normal (LLN) (ie, participant should have a normal lymphocyte count to enroll in the study).
• −Absolute neutrophil count ≤ 1,500 cells/mm3.
• −Platelet count ≤ 100,000 cells/mm3.
• −Participants with documented Gilbert's syndrome are to be excluded if total bilirubin is ≥ 3 × upper limit of normal (ULN) or direct bilirubin is \> ULN.
• −Aspartate aminotransferase (AST \[serum glutamic-oxaloacetic transaminase; SGOT\]) or alanine aminotransferase (ALT \[serum glutamic pyruvic transaminase; SGPT\]) \> 1.5 × ULN.
• −Alkaline phosphatase (ALP) levels \> 2.5 × ULN.
• −Hemoglobin \< 9.0 g/dL.
• −Serum creatinine \> 2.0 mg/dL or 177 μmol/L or creatinine clearance \< 40 mL/min (using the Cockcroft-Gault formula below):
• −Female = \[(140 - age in years) × weight in kg × 0.85\] / \[72 × serum creatinine in mg/dL\] Male = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\]
• −Have any of following:
• −Cirrhosis at a level of Child-Pugh B (or worse);
• −Cirrhosis (any degree) and a history of hepatic encephalopathy; or
• −Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
• −Participation in an investigational drug study within 21 days prior to the start of treatment on this study, except for hormone lowering therapy in participants with hormone-sensitive cancer. Participating in any other interventionalInterventional studyA study where participants are given something to see what happens.Read more → clinical trial during active participation in this clinical trial is not allowed.
• −Assessed by the InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → to be unable or unwilling to comply with the requirements of the protocol.
• −Confinement in an institution by order of a court or authority.
• −Inclusion CriteriaInclusion criteriaThe things you must have or be for a study to consider you.Read more →:
• −Able to understand and provide a signed informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → that fulfills the relevant IRBResearch Ethics Board (REB)The independent committee that must approve a study before it can run.Read more → or IEC guidelines.
• −Pathologically confirmed stage IV NSCLC disease.
• −Measurable tumor lesion(s) according to RECIST v1.1.
• −Have a life expectancy of at least 3 months.
• −Exclusion CriteriaExclusion criteriaThe things that would prevent someone from taking part.Read more →:
• −Autoimmune disease currently requiring systemic treatment (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma) except for autoimmune thyroiditis needing thyroid replacement and diabetes requiring insulin. The participant must have been off treatment for 60 days.
• −History of any of the following: drug-induced severe cutaneous adverse reaction (SCAR), including, but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), or dose-limiting immune-mediated reactions.
• −History of allogeneic hematopoietic stem cell transplant or organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring active treatment with systemic steroids or other systemic therapy; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (eg, prednisone or hydrocortisone) and corticosteroids used to manage AEs are permitted.
• −iii. Start or maintain antiviral treatment if clinically indicated as per the Investigator.
• −Active infection requiring systemic antibiotic therapy (antiviral therapy is allowed).
• −Have known active central nervous system (CNS) metastases, carcinomatous meningitis, and/or spinal cord compression.
• −Body weight ≤ 40 kg at screening.
• −Received a live vaccine ≤ 4 weeks prior to the first dose of study drug(s).
• −Inadequate organ function, evidenced by the following laboratory results:
• −Absolute lymphocyte count \< institutional LLN (ie, participant should have a normal lymphocyte count to enroll in the study).
• −Absolute neutrophil count ≤ 1,500 cells/mm3.
• −Platelet count ≤100,000 cells/mm3.
• −Total bilirubin \> 1.5 times the ULN, unless the participant has documented Gilbert's syndrome). Participants with documented Gilbert's syndrome are to be excluded if total bilirubin is ≥ 3 × ULN or direct bilirubin is \> ULN.
• −Aspartate aminotransferase (AST \[serum glutamic-oxaloacetic transaminase; SGOT\]) or alanine aminotransferase (ALT \[serum glutamic pyruvic transaminase; SGPT\]) \> 1.5 × ULN or \> 5 times ULN for participants with liver metastases.
• −Alkaline phosphatase (ALP) levels \> 2.5 × ULN, \> 5 times ULN for participants with known bone metastases.
• −Hemoglobin \< 9.0 g/dL.
• −Creatinine clearance \< 40 mL/min (using the Cockcroft-Gault formula below):
• −Female = \[(140 - age in years) × weight in kg × 0.85\] / \[72 × serum creatinine in mg/dL\] Male = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\]
• −Have any of the following:
• −Cirrhosis at a level of Child-Pugh B (or worse);
• −Cirrhosis (any degree) and a history of hepatic encephalopathy; or
• −Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
• −Participation in an investigational drug study within 28 days prior to the start of treatment on this study, except for hormone lowering therapy in participants with hormone-sensitive cancer. Participating in any other interventional clinical trial during active participation in this clinical trial is not allowed.
• −Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
• −Have a history of malignancy other than NSCLC, except:
• −Adequately resected non-melanoma skin cancer; or,
• −Curatively treated in situ disease or
• −Other curatively treated solid tumors, with no evidence of disease for ≥ 3 years; or
• −Other antineoplastic therapies intended to treat cancer, including herbal medicines or other prohibited concurrent medication(s) within 28 days prior to the start of treatment in the study.
• −Confinement in an institution by order of a court or authority.
• −ECOG performance status of 0 to 2.
• −Pregnant and nursing women.
• −Pregnant and nursing women.
• −Had major surgery within 28 days prior to study randomization. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating Investigator.
• −History of prior adverse reaction to immunotherapy that led to its permanent discontinuation.
• −Have acquired resistance to a regional Health Authority-approved immune plus platinum-based chemotherapy, defined as disease progression immediately following an initial response (of any duration) or stable disease (approximately 6 months duration \[± 2 weeks\]). Participants who received anti-PD-1/anti-PD-L1 mAb as first-line therapy may have received the combination of platinum-based chemotherapy and anti-PD-1/anti-PD-L1 mAb in the second line. Participants must have received platinum chemotherapy to be eligible. Participants must have received anti-PD-1/anti-PD-L1 mAb in their immediate prior line of therapy to be eligible.
• −Participants who receive an immune CPI as consolidation therapy after chemoradiation are eligible if they show progression or recurrence within 3 months of their last CPI and must have received at least 6 months of exactly 1 line of prior CPI therapy. If that CPI is not approved for advanced NSCLC, then an approved alternative CPI will be used.
• −If participants are positive for actionable genomic alteration (AGA), defined as a genomic alteration which has at least 1 regional Health Authority-approved targeted therapy. Participants MUST have received at least 1 targeted therapy or 2 or more if multiple lines of targeted therapies are approved in the region. Thus, participants must have exhausted regional Health Authority-approved targeted therapies for their specific AGA for first- or second-line NSCLC, then have acquired resistance to immune checkpoint therapy to be eligible. Participants must meet inclusion criteria #4.
• −Had major surgery, myocardial infarction, and/or cerebrovascular accident within 28 days prior to study randomization. Participants must have fully recovered from the effects of prior surgery or illness in the opinion of the treating Investigator.
• −History of prior adverse reaction to immunotherapy that led to its permanent discontinuation.
• −Hormone sensitive cancers treated only with hormone therapy.