Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer
Condition: HER2-mutant Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: neratinib; temsirolimus
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung cancer; Puma; neratinib; HKI-272; PB-272; Nerlynx

Summary:

      This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter,
      multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus
      combination therapy in patients with non-small cell lung cancer (NSCLC) who have documented
      somatic HER2 mutations.
    

Eligibility criteria:

        Inclusion Criteria

          1. Aged ≥18 years at the time of signing the informed consent.

          2. Histologically confirmed diagnosis of NSCLC, advanced (stage IIIB) or metastatic
             (stage IV).

          3. Documented somatic ErbB2 (HER2) activating mutation.

          4. Patients with anaplastic lymphoma kinase (ALK) translocations must have received
             crizotinib, except for cases of intolerable toxicity to crizotinib.

          5. At least one measurable lesion as defined by Response Evaluation Criteria in Solid
             Tumors version 1.1 (RECIST v1.1).

          6. Eastern Cooperative Oncology Group (ECOG) status <2.

          7. Left ventricular ejection fraction (LVEF) ≥50% measured by multiple -gated acquisition
             scan (MUGA) or echocardiogram (ECHO).

          8. Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women
             of reproductive capacity (those who are biologically capable of having children) and
             for women less than 12 months after menopause.

          9. Men and women of childbearing potential must agree and commit to the use of a highly
             effective method of contraception, as determined to be acceptable by the Investigator,
             from the time of informed consent until 3 months after the last dose of the
             investigational products.

         10. Provide written, informed consent to participate in the study and follow the study
             procedures.

        Exclusion Criteria

          1. Previous treatment with any investigational agent ≤14 days prior to the initiation of
             investigational products.

          2. Previous treatment with any strong inhibitor and/or inducer of CYP3A4 enzyme or
             sensitive P-glycoprotein (P-gp) substrates ≤30 days prior to the initiation of
             investigational products.

          3. Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart
             failure (New York Heart Association functional classification of ≥2), unstable angina,
             myocardial infarction within 12 months of enrollment, or ventricular arrhythmia.

          4. Major surgery <30 days of starting treatment.

          5. Chronic steroid use (prednisone >12.5 mg/day or dexamethasone >2 mg/day, excluding
             inhaled steroids).

          6. Currently breast feeding.

          7. Symptomatic or unstable brain metastases.

          8. QTc interval >0.450 seconds for men and >0.470 seconds for women, or known history of
             QTc prolongation or Torsades de Pointes (TdP).

          9. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g.,
             Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute [NCI] Common
             Terminology Criteria for Adverse Events Version 4.0 [CTCAE v.4.0] diarrhea of any
             etiology at baseline).

         10. Prior exposure to neratinib or mTOR inhibitor.

         11. Active infection or unexplained fever >38.5°C (101.3°F).

         12. Unable or unwilling to swallow tablets.

         13. Evidence of significant medical illness, abnormal laboratory finding, or psychiatric
             illness/social situations that would, in the Investigator's judgment, make the patient
             inappropriate for this study.

         14. Known hypersensitivity to any component of the investigational products.

         15. Unstable or uncontrolled diabetes mellitus (glycosylated hemoglobin [HbA1c] >6.5%).

         16. Screening laboratory assessments outside the following limits: ANC <1000/μL (<1.0 x
             109/L), Platelet count <75,000/μL (<75 x 109/L), Hemoglobin <8 g/dL, transfusions
             allowed, must be at least 7 days prior to baseline, Total bilirubin >1.5 x
             institutional upper limit of normal (ULN), AST and/or ALT 5 minutes, Creatinine
             clearance <50 mL/min.