Press Release: Third Novartis Phase III trial shows Kisqali(R) combination therapy significantly improves PFS in HR+/HER2- advanced breast cancer

Novartis International AG / Third Novartis Phase III trial shows

Kisqali(R) combination therapy significantly improves PFS in HR+/HER2-

advanced breast cancer. Processed and transmitted by Nasdaq Corporate

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announcement.

-- Kisqali plus fulvestrant demonstrated superior efficacy, with a median

PFS of 20.5 months vs. 12.8 months for fulvestrant alone, among overall

study population of first- and second-line postmenopausal patients with

HR+/HER2- advanced breast cancer[1]

-- In the subgroup of patients taking Kisqali plus fulvestrant in the

first-line setting, median PFS was not reached and 70% were estimated to

remain progression-free at median follow-up of 16.5 months[1]

-- MONALEESA-3 is the only randomized Phase III trial to study a CDK4/6

inhibitor plus fulvestrant in the first-line setting showing efficacy in

patients with de novo advanced breast cancer and those who had not

received adjuvant therapy in more than a year[1]

-- Data presented today at the 54th Annual Meeting of the American Society

of Clinical Oncology (ASCO) in Chicago and published simultaneously in

the Journal of Clinical Oncology

Basel, June 3, 2018 - Novartis today announced positive results from the

third Phase III trial of Kisqali(R) (ribociclib) in advanced or

metastatic breast cancer. MONALEESA-3 showed Kisqali plus fulvestrant

significantly prolonged progression-free survival (PFS) compared to

fulvestrant alone in postmenopausal women with hormone-receptor positive,

human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced

breast cancer. MONALEESA-3 is the largest phase III trial to evaluate

efficacy and safety of a CDK4/6 inhibitor plus fulvestrant in multiple

advanced breast cancer patient populations - first-line and second-line

settings[1]. These data will be presented today as an oral presentation

at the 54(th) Annual Meeting of the American Society of Clinical

Oncology (ASCO) in Chicago (Abstract #1000) and published simultaneously

in the Journal of Clinical Oncology.

Kisqali in combination with fulvestrant demonstrated a median PFS of

20.5 months (95% CI: 18.5-23.5 months) compared to 12.8 months (95% CI:

10.9-16.3 months) for fulvestrant alone (HR=0.593; 95% CI: 0.480-0.732;

p=.00000041) across both treatment arms. The median PFS for the subgroup

of patients receiving Kisqali plus fulvestrant in the first-line setting,

including only de novo patients and those whose disease relapsed >12

months since end of neo(adjuvant) endocrine therapy, was not reached

compared to 18.3 months for fulvestrant alone (HR=0.577; 95% CI:

0.415-0.802). In patients receiving treatment in the second-line setting,

or those who relapsed <12 months since end of neo(adjuvant) endocrine

therapy, the median PFS was 14.6 months compared to 9.1 months for

fulvestrant alone (HR=0.565; 95% CI: 0.428-0.744)[1].

"The MONALEESA-3 results in patients treated in this first-line setting

were particularly significant. Nearly 70% of women who received

ribociclib plus fulvestrant in this setting were estimated to remain

progression-free at the median follow-up of 16.5 months," said Dennis J.

Slamon, MD, Director of Clinical/Translational Research, University of

California, Los Angeles Jonsson Comprehensive Cancer Center. "In the

advanced breast cancer setting, it is important to ensure we provide

patients with treatment options that increase time to disease

progression while also maintaining quality of life."

Fifty percent of the women in MONALEESA-3 had lung and/or liver

metastases and showed a consistent treatment benefit compared with the

overall population. Follow-up to measure overall survival is ongoing as

these data remain immature[1].

"MONALEESA-3 data add to the robust body of evidence demonstrating the

broad potential of Kisqali to treat pre- and postmenopausal women living

with advanced breast cancer in various endocrine combinations and

multiple lines of therapy," said Samit Hirawat, MD, Head, Novartis

Oncology Global Drug Development. "These results along with the other

MONALEESA studies build a compelling case that Kisqali combination

therapy should be a cornerstone of first-line treatment of HR+/HER2-

advanced breast cancer."

No new safety signals were observed in the MONALEESA-3 trial; adverse

events were generally consistent with those observed in MONALEESA-2[1].

The discontinuation rate due to adverse events was 8.5% for Kisqali plus

fulvestrant compared to 4.1% for fulvestrant alone[1]. The most common

(>=5%) grade 3/4 adverse events in patients receiving Kisqali plus

fulvestrant compared to fulvestrant alone were neutropenia (53.4% vs 0%)

and leukopenia (14.1% vs 0%)[1].

Additional Kisqali data are being presented at the 2018 ASCO Annual

Meeting. Further results from MONALEESA-7 showed consistent treatment

benefit among premenopausal women with HR+/HER2- advanced breast cancer

regardless of prior chemotherapy treatment in the advanced setting

(Abstract #1047)[2]. Initial safety data from the CompLEEment-1 trial

demonstrated a consistent safety profile for Kisqali in a patient

population more reflective of those seen in a real-world setting

(Abstract #1056)[3]. Lastly, biomarker data from MONALEESA-2 showed that

clinical benefit of Kisqali was consistent across gene expression

subgroups with a trend toward greater Kisqali benefit in the high versus

low ESR1 expression and low versus high RTK expression subgroups

(Abstract #1022)[4].

Novartis is in discussion with the US Food and Drug Administration (FDA)

with respect to a supplemental New Drug Application (sNDA), seeking

approval of Kisqali plus fulvestrant for the treatment of postmenopausal

women with HR+/HER2- advanced breast cancer.

About MONALEESA-3

MONALEESA-3 is a Phase III randomized, double-blind, placebo-controlled

study evaluating Kisqali in combination with fulvestrant compared to

fulvestrant alone for the treatment of postmenopausal women with

HR+/HER2- advanced breast cancer who received no prior or only one line

of prior endocrine therapy for advanced disease. A total of 726 people

were randomized in the trial, including first-line patients comprised of

367 women who were treatment-naïve and 345 who had received up to

one line of prior endocrine therapy for advanced disease. Patients were

randomized (2:1) to receive Kisqali plus fulvestrant or fulvestrant

alone. Randomization was stratified by the presence or absence of lung

or liver metastases and prior endocrine therapy (first-line versus

second-line).

About Kisqali(R) (ribociclib)

Kisqali is a selective cyclin-dependent kinase inhibitor, a class of

drugs that help slow the progression of cancer by inhibiting two

proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins,

when over-activated, can enable cancer cells to grow and divide too

quickly. Targeting CDK4/6 with enhanced precision may play a role in

ensuring that cancer cells do not continue to replicate uncontrollably.

Kisqali was approved by the US Food and Drug Administration in March

2017 and by the European Commission in August 2017, as initial

endocrine-based therapy for postmenopausal women with HR+/HER2- locally

advanced or metastatic breast cancer in combination with an aromatase

inhibitor based on findings from the pivotal MONALEESA-2 trial. Kisqali

is not currently approved for use in combination with fulvestrant or in

premenopausal women.

Kisqali is approved for use in 59 countries around the world, including

the United States and European Union member states. Kisqali was

developed by the Novartis Institutes for BioMedical Research (NIBR)

under a research collaboration with Astex Pharmaceuticals.

About the Kisqali Clinical Trial Program

With more than 2,000 patients enrolled in current trials, the MONALEESA

program is the largest industry sponsored Phase III clinical program

researching a CDK4/6 inhibitor in HR+/HER2- advanced breast cancer. In

addition to MONALEESA-3, there are three other Phase III trials

evaluating Kisqali combination therapy.

MONALEESA-7 is a Phase III randomized, double-blind, placebo-controlled

trial investigating the efficacy and safety of Kisqali in combination

with tamoxifen or a non-steroidal aromatase inhibitor plus goserelin

versus tamoxifen or an aromatase inhibitor plus goserelin, in

premenopausal or perimenopausal women with HR+/HER2- advanced breast

cancer who had not previously received endocrine therapy for advanced

disease.

MONALEESA-2 is a Phase III global registration trial evaluating Kisqali

in combination with letrozole compared to letrozole alone in

postmenopausal women with HR+/HER2- advanced breast cancer who received

no prior therapy for their advanced breast cancer.

CompLEEment-1 is an open-label, multicenter, Phase IIIb study evaluating

the safety and efficacy of Kisqali plus letrozole in pre- or

postmenopausal women and men with HR+/HER2- advanced breast cancer who

have not received prior hormonal therapy for advanced disease.

More information about these studies can be found at

www.ClinicalTrials.gov.

About Novartis in Advanced Breast Cancer

For more than 30 years, Novartis has been tackling breast cancer with

superior science, great collaboration and a passion for transforming

patient care. With one of the most diverse breast cancer pipelines and

one of the largest numbers of breast cancer compounds in development,

Novartis leads the industry in discovery of new therapies and

combinations, especially in HR+ advanced breast cancer, the most common

form of the disease.

Important Safety Information from the Kisqali EU SmPC

The most common ADRs and the most common grade 3/4 ADRs (reported at a

frequency >=20% and >=2% respectively) for which the frequency for

Kisqali plus letrozole exceeds the frequency for placebo plus letrozole

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June 03, 2018 09:00 ET (13:00 GMT)