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New Data from GEOMETRY mono-1 Study Show Clinically Meaningful Results in Patients with Non-Small Cell Lung Cancer with MET exon-14 Skipping Mutation Treated with Capmatinib

June 3, 2019 Off By BusinessWire

Primary efficacy analysis demonstrated promising efficacy for
capmatinib irrespective of the prior line of therapy in 97 patients:
overall response rate was 68 percent and 41 percent and median
duration of response was 11.14 months and 9.72 months, respectively,
across treatment-naive and previously-treated patients with locally
advanced or metastatic non-small cell lung cancer (NSCLC) harboring a
MET exon-14 skipping mutation
The U.S. Food and Drug Administration recently granted capmatinib
Breakthrough Therapy designation for the treatment of patients with
metastatic NSCLC harboring a MET exon-14 skipping mutation with
disease progression on or after platinum-based chemotherapy
Novartis has exclusive worldwide development and commercialization
rights to capmatinib

WILMINGTON, Del.–(BUSINESS WIRE)–$INCY #ASCO19–Incyte (Nasdaq:INCY) today announced primary efficacy results from the
Novartis-sponsored GEOMETRY mono-1 Phase 2 clinical trial of
capmatinib, an investigational, selective MET inhibitor. The results
demonstrate that capmatinib shows promise as a potential treatment
option for patients with locally advanced or metastatic non-small cell
lung cancer (NSCLC) that harbor a MET exon-14 skipping mutation. There
are currently no approved targeted therapies to treat this particularly
aggressive form of NSCLC.

Results of the Phase 2 study will be presented at an oral session today,
June 3, 2019, at the American Society of Clinical Oncology (ASCO) 2019
Annual Meeting at 8:00 a.m. CDT (Abstract #9004)¹.

GEOMETRY mono-1 is an international, prospective, multi-cohort,
non-randomized, open-label study evaluating 97 adult patients with
locally advanced or metastatic NSCLC harboring a MET exon-14 skipping
mutation who received capmatinib tablets 400 mg orally twice daily.
Primary efficacy results among treatment-naïve patients (Cohort 5b: 28
patients) included a 68 percent overall response rate (ORR) based on the
Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1
(95% [CI: [47.6-84.1]) and 41 percent of previously-treated NSCLC
patients (Cohort 4: 69 patients) also responded (95% CI: [28.9 – 53.1]).
Data on median duration of response (DOR), a key secondary endpoint, was
11.14 months (95% CI: [5.55-NE]) and 9.72 months (95% CI: [5.55-12.98]),
in the treatment-naïve and previously-treated groups, respectively.
Intracranial activity in 54 percent (n=7/13) of patients, including some
cases of complete resolution of brain lesions, was also observed by ad
hoc neuro-radiologist review in patients with brain lesions. All results
were based on independent assessment by the BIRC, and all tumor CT scans
were evaluated in parallel by two radiologists to confirm the response.

The most common treatment-related adverse events (AE) (≥10% all grades)
across all cohorts (n=334), were peripheral edema (42%), nausea (33%),
creatinine increase (20%), vomiting (19%), fatigue (14%), decreased
appetite (13%) and diarrhea (11%); the majority of the AEs were grades
1/2.

“In the absence of approved targeted therapies, patients with advanced
or metastatic NSCLC harboring a MET exon-14 skipping mutation must rely
on existing treatment approaches and, as a result, face a particularly
poor prognosis,” said Steven Stein, M.D., Chief Medical Officer, Incyte.
“The results of the GEOMETRY mono-1 study to be presented at ASCO
underscore the potential of capmatinib to meaningfully improve outcomes
for this underserved subset of NSCLC patients.”

The U.S. Food and Drug Administration (FDA) recently granted capmatinib
Breakthrough Therapy designation for patients with metastatic NSCLC
harboring a MET exon-14 skipping mutation with disease progression on or
after platinum-based chemotherapy. Previously, both the U.S. FDA and
Japan’s Pharmaceuticals and Medical Devices Agency recognized capmatinib
with Orphan Drug status. It is estimated that 3 to 4 percent of all
patients with NSCLC have an identified MET mutation².

Novartis expects to submit a new drug application to the FDA for
capmatinib as a treatment for patients with advanced NSCLC harboring a
MET mutation in 2019.

About GEOMETRY mono-1

The Novartis-sponsored GEOMETRY mono-1 trial is an international,
prospective, multi-cohort, non-randomized, open-label Phase 2 study to
evaluate the efficacy and safety of single-agent capmatinib in adult
patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC
harboring a MET amplification and/or mutation. Patients with locally
advanced or metastatic NSCLC harboring a MET exon-14 skipping mutation
(centrally confirmed) were assigned to Cohorts 4 (previously treated
patients) or 5B (treatment-naïve), regardless of MET amplification/gene
copy number and received 400 mg capmatinib tablets orally twice daily.

The primary endpoint was ORR based on BIRC assessment per RECIST v1.1.
The key secondary endpoint was DOR by BIRC. The GEOMETRY mono-1
study found an ORR in the treatment-naïve patients (n=28) of 67.9
percent (95% CI: [47.6 – 84.1]) and an ORR of 40.6 % (95% CI: [28.9 –
53.1]) in the previously treated patients (n=69). Median DOR was 11.14
months (95% CI: [5.55-NE]) in treatment-naïve patients and 9.72 months
(95% CI: [5.55-12.98]) in previously treated patients¹.

The most common treatment-related AEs included peripheral edema, nausea,
creatinine increase and vomiting. Of patients treated with capmatinib,
84 percent experienced an AE, with 36 percent having grade 3/4 AEs (only
4.5% were Grade 4)¹.

About Capmatinib

Capmatinib is an investigational, oral and selective MET inhibitor
discovered by Incyte that was licensed to Novartis in 2009. Under the
terms of the Agreement, Incyte granted Novartis exclusive worldwide
development and commercialization rights to capmatinib and certain
back-up compounds in all indications. If capmatinib is successfully
developed by Novartis, Incyte may become eligible for over $500 million
in future milestones as well as royalties of between 12 and 14 percent
on global sales by Novartis.

About Incyte

Incyte Corporation is a Wilmington, Delaware-based biopharmaceutical
company focused on the discovery, development and commercialization of
proprietary therapeutics. For additional information on Incyte, please
visit the Company’s website at www.incyte.com.

Follow @Incyte on Twitter at https://twitter.com/Incyte.

Forward-Looking Statements

Except for the historical information set forth herein, the matters set
forth in this press release, including statements regarding the ongoing
clinical development program for capmatinib and its potential in
treating NSCLC, Novartis’ plans to submit an NDA for capmatinib and the
expected timing of such filing, and whether and when Incyte may receive
milestone payments or royalties from Novartis relating to capmatinib,
contain predictions, estimates and other forward-looking statements.

These forward-looking statements are based on the Company’s current
expectations and subject to risks and uncertainties that may cause
actual results to differ materially, including unanticipated
developments and the risks related to the efficacy or safety of the
Company’s development pipeline, the results of further research and
development, the high degree of risk and uncertainty associated with
drug development, clinical trials and regulatory approval processes,
other market or economic factors and competitive and technological
advances; and other risks detailed from time to time in the Company’s
reports filed with the Securities and Exchange Commission, including its
Form 10-Q for the quarter ending March 31, 2019. Incyte disclaims any
intent or obligation to update these forward-looking statements.

References

1. Juergen Wolf. Capmatinib (INC280) in METΔex14-mutated advanced
non-small cell lung cancer (NSCLC): efficacy data from the Phase 2
GEOMETRY mono-1 study. Abstract #9004. 2019 American Society of
Clinical Oncology Annual Meeting (ASCO), May 31-June 4, 2019, Chicago,
IL.

2. Salgia R. MET in Lung Cancer: Biomarker Selection Based on Scientific
Rationale. Mol Cancer Ther. 2017;16(4):555-565.