Novel therapy shows promise for lung cancer patients with rare EGFR
mutation

Date:
August 3, 2021
Source:
H. Lee Moffitt Cancer Center & Research Institute
Summary:
Researchers report on a multinational, early phase clinical trial
evaluating a new targeted therapy for patients with metastatic
or unresectable non-small cell lung cancer who have a specific
genetic mutation: EGFR Ex20Ins.



FULL STORY ==========================================================================
Lung cancer is the leading cause of cancer death among men and women in
the United States, regardless of ethnicity. Non-small cell lung cancer
is the most common form of the disease, accounting for 84% of all
diagnoses. One option for this group of patients is targeted therapy,
a type of treatment that attacks specific genes and proteins within a
cancer cell. Moffitt Cancer Center is part of a multinational, early
phase clinical trial evaluating a new targeted therapy for patients
with metastatic or unresectable non-small cell lung cancer who have a
specific genetic mutation: EGFR Ex20Ins.


========================================================================== CHRYSALIS is a phase 1, open label, dose escalation and dose expansion
trial evaluating amivantamab, a bispecific antibody with immune cell
directing activity designed to engage two distinct driver pathways in
non-small cell lung cancer: EGFR and MET. The novel therapy has already received Breakthrough Therapy Designation by the U.S. Food and Drug Administration based on preliminary efficacy data. New expanded data
from the trial was published in the Journal of Clinical Oncology.

Mutations in the epidermal growth factor receptor (EGFR) gene are the most common targetable genomic drivers of non-small cell lung cancer. The role
of EGFR is to help cells grow and divide. However, when EGFR is mutated,
cell growth goes unchecked, allowing abnormal cells the opportunity
to grow and multiply. There are several types of EGFR mutations. One
type, EGFR exon 20 insertion (EGFR Ex20Ins), is seen in less than 10% of patients, but those with this specific EGFR mutation have poorer outcomes
and don't respond to FDA- approved targeted therapies, such as tyrosine
kinase inhibitors. In addition, therapies are needed for patients whose
tumors progress on experimental inhibitors for EGFR Ex20Ins.

"We have successfully developed targeted therapies for other types of
EGFR mutations, but those therapies have less benefit for patients
with the EGFR Ex20Ins mutation. Platinum-based chemotherapy remains
the standard of care treatment for this group," said Eric Haura, M.D.,
study author and associate center director of Clinical Science at Moffitt.

Accurate detection of EGFR Ex20Ins mutations is critical to identify
patients with lung cancer who are most likely to respond to EGFR Ex20Ins targeted therapy. Smaller targeted assays may not identify all EGFR
Ex20Ins mutations.

The Moffitt STAR[TM] (Solid Tumor Actionable Result) genomics panel, a comprehensive next generation sequencing platform, precisely identifies patients with EGFR Ex20Ins mutations who may benefit from EGFR Ex20Ins
targeted therapy.

The new expanded data of the CHRYSALIS study included 81 patients. The
overall response rate, meaning the portion of patients who responded
to the therapy, was 40%. Three patients had a complete response,
meaning there was no evidence of disease, and 29 patients saw a partial response. The median duration of response was 11.1 months, with 20
patients having responses of at least six months or greater.

"The results from the study are encouraging, as we're seeing durable
responses among patients with a hard-to-treat subtype of non-small cell
lung cancer," said Haura. "In addition, we have seen responses in patients
who have had prior therapy directed against these rare EGFR mutations."
Ongoing studies with amivantamab continue at Moffitt for EGFR mutant
and MET mutant lung cancer patients, and opportunities for this drug in
other cancer types are being explored.

This study was funded by Janssen R&D LLC.

========================================================================== Story Source: Materials provided by H._Lee_Moffitt_Cancer_Center_&_Research_Institute. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Keunchil Park, Eric B. Haura, Natasha B. Leighl, Paul Mitchell,
Catherine
A. Shu, Nicolas Girard, Santiago Viteri, Ji-Youn Han, Sang-We Kim,
Chee Khoon Lee, Joshua K. Sabari, Alexander I. Spira, Tsung-Ying
Yang, Dong- Wan Kim, Ki Hyeong Lee, Rachel E. Sanborn, Jose'
Trigo, Koichi Goto, Jong-Seok Lee, James Chih-Hsin Yang, Ramaswamy
Govindan, Joshua M. Bauml, Pilar Garrido, Matthew G. Krebs, Karen
L. Reckamp, John Xie, Joshua C.

Curtin, Nahor Haddish-Berhane, Amy Roshak, Dawn Millington,
Patricia Lorenzini, Meena Thayu, Roland E. Knoblauch, Byoung Chul
Cho. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell
Lung Cancer Progressing on Platinum Chemotherapy: Initial Results
From the CHRYSALIS Phase I Study. Journal of Clinical Oncology,
2021; JCO.21.00662 DOI: 10.1200/ JCO.21.00662 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210803105526.htm

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