Her2-positive Lung Cancer Treated With Dedicated Drug

Inclusion Criteria

• •1. Patient having signed an informed consent form
• •2. Histologically or cytologically confirmed NSCLC (per 2015 8th edition TNM classification)
• •3. Not suitable for radiation, inoperable stage III or stage IV
• •4. HER2 exon 20 mutation or insertion among which: in-frame insertions in exon 20 between codons 775 and 881 including the 12bp insertion with a duplication / insertion of 4 amino acids (YVMA) at codon 775, the 3bp insertion with a complex insertion-substitution G776\>VC and point mutations L755S and G776C. Other mutation/insertion should be discussed with IFCT. Analysis must be performed in INCa-labelled laboratories or platforms according to a validated procedure.
• •5. Prior treatment with at least one regimen of platinum-based chemotherapy with documented disease progression.
• •Note: taxanes are allowed provided that no grade \>2 associated adverse event occurred (except hematological toxicity).
• •6. Presence of at least one lesion that can be measured by CT scan (RECIST v1.1)
• •7. Age ≥ 18 years
• •8. Adequate organ function, as evidenced by the following laboratory results:
• •ANC \> 1500 cells/mm3 Platelet count \> 100,000 cells/mm3 Hemoglobin \> 9.0 g/dL Patients are allowed to receive transfused RBC to achieve this level. Total bilirubin ≤ 1.5 × ULN, except in patients with previously documented Gilbert's syndrome, in which case the direct bilirubin should be less than or equal to the ULN SGOT and SGPT ≤ 2.5 × ULN Alkaline phosphatase ≤ 2.5 × ULN, Alkaline phosphatase \< 5×ULN and SGOT and SGPT \< 5×ULN for patients with hepatic and/or bone metastases Clearance creatinine ≥ 30 mL/min INR and aPTT ≤ 1.5 x ULN This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
• •9. WHO performance index of 0, 1 or 2
• •10. LVEF ≥ 50%
• •11. Patient who is capable, according to the investigator, of complying with the study's requirements and restrictions
• •12. Estimated life expectancy \> 3 months
• •13. A female is eligible to enter and participate in this study if she is of:
• •Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has undergone:
• •* Hysterectomy.
• •* Bilateral oophorectomy (ovariectomy).
• •* Bilateral tubal ligation.
• •* Or who is post-menopausal:
• •* Patients not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone value \>40 mIU/mL and an estradiol value \<40 pg/mL (\<140 pmol/L).
• •* Patients must discontinue HRT prior to study enrolment due to the potential for inhibition of cytochrome enzymes that metabolize estrogens and progestins. For most forms of HRT, at least 2 4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT. If a female subject is determined not to be post-menopausal, they must use adequate contraception, as defined immediately below.
• •Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception during the study and for at least 7 months after the last dose of investigational product. Contraceptive methods acceptable to IFCT, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:
• •* A non-hormonal intrauterine device with a documented failure rate of less than 1% per year.
• •* Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
• •* Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 7 months after the last dose of investigational product.
• •* Two effective forms of non-hormonal contraception (condom with spermicidal jelly, foam suppository or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).
• •Note: Oral contraceptives are not allowed.
• •14. Female patients who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 15 days following the last dose of study drug.
• •15. A male with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study and for at least 7 months after the last dose of investigational product.
• •16. Patient will be eligible for inclusion in this study only if either affiliated to or a beneficiary of social security insurance.