...Patient is positive for EGFR or HER2 exon 20 mutations based on tissue testing:...

...NSCLC with documented EGFR exon 20 mutation by one of the following Clinical Laboratory Improvement Act (CLIA) certified tests: OncoMine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay or by a Food and Drug Administration (FDA) approved device using cobas EGFR mutation test version (v)2 or therascreen EGFR RGQ PCt kit; Mutations include D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH, or any other exon 20 in-frame insertion or point mutation excluding T790M...

...- Cohort 1 and 3: Documented EGFR exon 20 insertion mutation...

...- Phase 2: Documented EGFR or HER2 exon 20 insertion mutations (including duplication mutations) in NSCLC patients -...

Among EGFR ex20ins patients, 71/84 had stage IV disease....Nine out of 10 patients who received poziotinib and all 5 patients who received mobocertinib had either a partial response or stable disease, whereas 3/7 patients who received afatinib had stable disease.

We report a phase II study of 50 advanced non-small cell lung cancer (NSCLC) patients with point mutations or insertions in EGFR exon 20 treated with poziotinib (NCT03066206)....these data demonstrate that poziotinib is a clinically active and tolerable inhibitor of EGFR exon 20 insertion mutations with meaningful clinical activity in platinum-refractory patients, for whom limited therapeutic options are currently available...

POZ showed a clinical activity in aNSCLC EGFR/HER2 ex20-ins aNSCLC pts.

Twenty-three pts had EGFR ex20-ins while 8 had HER2 ex20-ins. Five pts received poziotinib as first line treatment and 26 as second or further-line therapy. Objective response rate (ORR) and disease control rate (DCR) for POZ were 31 and 79%, respectively....POZ showed a clinical activity in EGFR or HER2 ex20-ins NSCLC pts irrespective of the treatment line.

Poziotinib exhibited clinically meaningful CNS activity in patients with EGFR or HER2 exon 20 mutations in ZENITH20 Cohorts 1-3. The majority of the patients had no CNS progression and 3/36 patients had intracranial complete responses. The preliminary data suggest that poziotinib may provide a meaningful treatment alternative for patients with NSCLC that harbor EGFR or HER2 exon 20 mutations and who present with CNS metastases that have poor prognosis.

ZENITH20 enrolled previously treated and naïve patients with advanced/metastatic NSCLC and EGFR or HER2 exon 20 insertion mutations in several cohorts…Poziotinib (16 mg) was administered orally QD...In NSCLC patients that had baseline CNS lesions (N=36), the analysis showed a patient-based ORR of 22.2% (8/36) and a DCR of 88.9% (32/36). One patient in each cohort had a complete intracranial response and stable disease was 80.6% across 3 cohorts and 92.9% in C2....

The ORR was 30% (EGFR/HER2: 23/50%) and DCR 80%....Poziotinib exhibited effects in mNSCLC patients with EGFR/HER2-exon 20-i-mut.

...analysis showed an ORR of 27.8% (22/79; 95% CI: 18.4 – 39.1%) and disease control rate of 86.1%. 91% of all study patients had tumor reduction. The median DOR was 6.5 months and the median PFS was 7.2 months....Poziotinib demonstrated clinically meaningful activity in treatment-naïve mNSCLC patients with EGFR exon 20 mutations at 16 mg QD dosing.

...Poziotinib (16 mg) was administered orally, once daily (QD)...Clinical activity was observed in previously treated patiens in both NSCLC EGFR or HER2 exon 20 mutations regardless of specific mutations and prior therapy with consistent responses seen in more heavily pre-treated patients.

POZ (16 mg or less) was administrated orally...The ORR was 27.6% (EGFR 19%, HER2 50%) and DCR 69% confirmed by a central review….POZ demonstrated clinical activity in mNSCLC pts with EGFR and HER2 exon 20 i-mut.

The ORR in the as-treated population was 14.8% (95% CI 8.9 - 22.6%), and the DCR was 68.7% (95% CI 59.4 - 77.0%) with a median DoR of 7.4 months. 65% patients had tumor size reductions and the median PFS was 4.2 months. In the evaluable population (n = 88), the ORR was 19.3% and the unconfirmed ORR was 25%. Responses were predominantly observed in insertions between residues M766 to D770 of exon 20 (8/44; 18.2%).

We evaluated the efficacy and safety of poziotinib in previously treated NSCLC patients with EGFR exon 20 insertion mutations...Although the ORR primary endpoint was not met, poziotinib induced tumor size reduction in the majority (65%) of patients. The tumor size reduction combined with long duration of response demonstrated the clinical activity of poziotinib in treating this patient population.

...a former smoker 62-year-old female patient was diagnosed with relapse, after two surgeries and post-operative chemotherapy of mNSCLC...Given the identification by Next Generation Sequencing (NGS) of EGFRex20ins mutation...Since the first reevaluation (after 4 weeks of therapy), the treatment with poziotinib resulted to be remarkably effective, with a partial response (PR) subsequently confirmed in May and July 2021.