Poziotinib in Stage IV Lung Adenocarcinoma With HER2 Mutation (KASTT001)

A Phase II Study to Assess Efficacy of Pan-HER Inhibitor (HM781-36B, Poziotinib) in Stage IV Lung Adenocarcinoma With HER2 Mutation

In this trial, treatment efficacy and safety of Poziotinib will be assessed in patients with stage IV lung adenocarcinoma harboring HER2 mutation.

This study is designed to be multi-center, open-label, single-arm, prospective, phase II trial of patient with stage IV lung adenocarcinoma with HER2 mutation who have not received prior EGFR-TKI. Approximately 47 patients will be enrolled into the trial, and expected study duration is 36 months from IRB and Korea: MFDS approval date.

The study drug(poziotinib) will be administered orally as one 12 mg tablet once a day until disease progression or manifestation of unacceptable toxicity. The initial dose of the study drug 12 mg daily can be reduced to 8 mg once daily according to dose reduction criteria in protocol. A cycle of study treatment is defined as 28 days.

Inclusion Criteria:

1. lung adenocarcinoma, stage IV

2. Patients with HER2 mutation by sequencing

   - Confirmed triple-negative patients with remnant tumor DNA

3. Patients who have histories of previous exposure to at least one more systemic chemotherapies (not EGFR-TKI)

4. ECOG performance status 0~2

5. Patient with at least one measurable lesions according to RECIST

6. Patients who have proper organ functions as follows

   • Neutrophil count: > 1,500/uL
   • Platelet count: > 100,000/uL
   • Hb: > 9.0g/dL
   • AST/ALT : < 2.0 x upper normal limit
   • Bilirubin: < 1.25 x upper normal limit
   • Serum creatinine : < upper normal limit

Exclusion Criteria:

1. Expected lie expectancy < 3 months
2. CNS metastasis or spinal cord compression which were not treated with operation and/or radiation therapy(but, Patient with medically stable condition after operation and/or radiation therapy, or without symptomatic metastasis of brain in accordance with the investigator's judgment could participate in the study)
3. Patients who have severe or unstable systemic disease in accordance with the investigator's judgment(ex, unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
4. Patients who have histories of previous exposure to EGFR-TKI