ASCO Annual Meeting 2021 Recap: Xiuning Le, MD, PhD on Poziotinib, ZENITH20 Cohort 1 Analysis, and Central Nervous System (CNS) Penetration

Posted on: 2021-06-06 15:25:45

What follows are the remarks of ZENITH20 (poziotinib) Principal Investigator Xiuning Le, MD, PhD, thoracic oncologist at The University of Texas MD Anderson Cancer Center, on efficacy data from ZENITH20's cohort #1 subgroup analysis (ASCO 2021 Annual Meeting):

Good morning. We think the ASCO selection committee for this opportunity to present the phase 2 study of poziotinib in non-small cell lung cancer with EGFR exon 20 insertions. EGFR exon 20 insertions represent about 10% of all EGFR mutations non-small cell lung cancers. But there are no FDA approved medications for this patient population. ZENITH20 study is a multi-center, multi-cohort phase 2 trial of poziotinib in patients with non-small cell lung cancer harboring EGFR or HER2 exon 20 insertions.

00:41Today, I am presenting the efficacy data on the subgroup analysis from cohort one, which is the previously treated EGFR exon 20 insertion cohort. In the intent to treat the population of 115 patients, the objective response rate by independent review committee was a 14.8% and a disease control rate was 68.7%. Among them, 27 patients were not evaluable, including 11 patients did not have measurable disease, and 16 patients did not receive post treatment restaging scans. In the 88 evaluable patients, the response rate was 19.3% and the disease control rate was 80.7%. The duration of response was 7.4 months, and the PFS was 4.2 months.

01:44Response by prior lines of therapy is shown here. In this previously treated population, about one third of patients had three or more lines of therapy. In those heavily pretreated patients, the response rate was at 22%, similar to slightly higher than in patients who received one to two lines of prior therapy.

02:07This cohort of patients had a variety of prior therapies, including prior first and the [INAUDIBLE] EGFR TKI. Response was seen in patients who had the prior EGFR TKI, including one confirmed response in the patient progressed on osimertinib. Response rate in patients who did not have EGFR TKI was 23%.

02:34EGFR exon 20 insertions are heterogeneous at the molecular level. [? Robicheaux ?] et al. has previously classified them as near-loop or far-loop insertions based on their distance to C-helix, with a dividing line between 772 and the 773. Insertions between codon 762 to 766 are considered as a helical insertions.

03:02Cohort one patients' molecular distribution of EGFR exon 20 insertions was consistent with the previously reported frequency, with a near-loop insertion as having the highest incidence. The waterfall plot was color coded by insertion status. Poziotinib conferred a clinical benefit to EGFR exon 20 insertions at all positions. Responses and tumor reductions were seen in both near-loop and the far-loop insertions.

03:33Clinical benefit from poziotinib by individual insertion was shown on the right. The single most common alteration was the 769 insertion, with a disease control rate of 87%. This cohort was not powered for statistical difference among the molecular subgroups.

03:57In this cohort of 115 patients, 12 had the baseline brain metastases. 10 out of the 12 had no CNS progression. Among the 103 patients who did not have CNS brain metastases at baseline, only three developed new brain lesions on poziotinib treatment.

04:18This case shown here is a good representation of a typical patient in cohort one. She is a 66-year-old non-smoker female, with a prior chemo- and immunotherapy who received poziotinib for her EGFR near-loop 768 duplication. She achieved stable disease with tumor reduction of 27% by resist criteria. Her brain metastases were stable to decreased throughout the time she was on poziotinib for eight months. The patient eventually progressed due to liver metastases.

04:59In conclusion, poziotinib has demonstrated clinical activity in previously treated lung cancer patients with EGFR exon 20 insertions. Patients with multiple prior lines of therapy derived a benefit. EGFR exon 20 insertions at oppositions benefited from poziotinib. And poziotinib showed clinical activity in patients with CNS metastases. Thank you.

End of Dr. Le's remarks


For those who aren't on Twitter, here is what I tweeted:

Stellar poziotinib PI @LeXiuning delivers super news for Cohort 1 pretreated EGFR ex20ins. Benefit to ALL insertions, reducing tumor burden in BOTH near-loop & far-loop insertions; DCR of 87% for 769! 10 of the 12 pts w/brain mets: no CNS progression!!  Pozi on a roll!


Our cherished Elena Siltanen, Pharm.M.Sc., of blessed memory, would have loved Dr. Le's presentation.  As Chair of our Angel Buddy Program, Elena was a firm believer in never hesitating to enroll in an appropriate clinical trial.  As she stated to many of you working with patients one-on-one and posting in our Exon 20 Group social media groups, she understood that because the Exon 20 Group would do all it could to make the patient's journey on that trial drug easier, patients should have a comfort level to screen for any of the clinical trials that are available.  Because of Elena and the support of the Exon 20 Group, some of you were able to screen for the ZENITH20 trial and go onto pozi and remain on the drug for a long time before disease progression--whether accessing the drug through expanded access or by entering ZENITH20.  As we say over and over again, "it's all in the management."

We are very encouraged not only from the twice a day dosing regimen for pozi but from the increasingly better mitigation strategies now in use across many community practices and medical centers, some of which were inspired by Elena as well as some of the leading principal investigators who have worked with poziotnib patients since 2017-2018.

As always, please call (1-602-618-0183) or write the Exon 20 Group ( for any questions/comments/update on your exon 20 journey or your loved one's situation.



Marcia Horn, Executive Director, Exon 20 Group