Spectrum Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for poziotinib for the treatment of non-small cell lung cancer (NSCLC) in previously treated patients with HER2 exon 20 mutations.

...Have documentation of HER2 exon 20 mutation 6....

Patients with HER2 exon 20 NSCLC who previously received 2+ lines of systemic therapy were enrolled in 2 cohorts of ZENITH20. Poziotinib was administered orally either as 16 mg QD or 8 mg BID until disease progression or toxicity….In 35 patients that had a prior HER2 therapy, the ORR was 29%; DCR was 71%; median DOR was 5.5 m and median PFS was 5.6 m....Poziotinib demonstrated clinically meaningful efficacy in patients who received prior 2+ lines of therapy including HER2 therapy.

Poziotinib demonstrated clinically meaningful efficacy in patients who received and progressed on prior 2+ lines of therapy regardless of types and sequence of treatment. ZENITH20 study provides a large dataset in the 3rd or later line setting of HER2 exon 20 mutations NSCLC patients who have very limited treatment options. No new safety signal was detected in this patient population.

ZENITH20, a multicenter, multicohort, open-label phase II study, evaluated poziotinib in patients with advanced or metastatic NSCLC….With a median follow-up of 9.0 months, objective response rate was 27.8% (95% CI, 18.9 to 38.2); 25 of 90 patients achieved a partial response. Disease control rate was 70.0% (95% CI, 59.4 to 79.2)....Poziotinib demonstrates antitumor activity in previously treated patients with HER2 exon 20 insertion NSCLC.

Responses were observed across HER2 exon 20 mutation subtypes. The median duration of response was 5.0 months (95% CI, 4.0 to not estimable). The median progression-free survival was 5.5 months (95% CI, 4.0 to 7.0). The median overall survival was 15 months (95% CI, 9.0 to not estimable)....Poziotinib showed promising antitumor activity in patients with HER2 exon 20 mutant NSCLC including patients who had previously received platinum-based chemotherapy.

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.

...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.

Poziotinib demonstrated clinical activity in mNSCLC patients with EGFR/HER2-exon 20-i-mut…

In a heavily pre-treated population with HER2 exon 20 mutant NSCLC, poziotinib provides high ORR, encouraging PFS, and manageable toxicity profile. 

In heavily pre-treated population with EGFR and HER2 exon 20 mutant NSCLC, poziotinib demonstrated encouraging antitumor activity in both TKI-naive and -refractory patients, and manageable toxicity profile.

Overall, poziotinib was the most potent HER2 mutant-selective TKI tested. Phase II clinical testing in ERBB2 exon 20-mutant non-small cell lung cancer resulted in a confirmed objective response rate of 42% in the first 12 evaluable patients.