On May 27, 2020 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported interim safety, tolerability and efficacy data from the ongoing expansion portion of the Phase 1 study evaluating XMT-1536, its first-in-class ADC candidate targeting NaPi2b, in patients with ovarian cancer and non-small cell lung (NSCLC) adenocarcinoma (Press release, Mersana Therapeutics, MAY 27, 2020, View Source [SID1234558524]). The Company will host a conference call and webcast today, Wednesday, May 27, 2020, at 8:00 a.m. ET during which investigator Debra L. Richardson, MD, Associate Professor of Gynecologic Oncology at the Stephenson Cancer Center at the University of Oklahoma Health Sciences Center and the Sarah Cannon Research Institute and members of the Mersana executive team will present and discuss these data. These data will also be presented in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program on Friday, May 29, 2020 starting at 8:00 a.m. ET.

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"These data demonstrate not only that XMT-1536, our first-in-class Dolaflexin ADC targeting NaPi2b, can deliver confirmed complete responses, partial responses and durable stable disease in platinum-resistant ovarian cancer, but also that these responses can deepen over time in a patient population with poor prognosis and limited treatment options," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "XMT-1536 continues to demonstrate that it is generally well tolerated, without the dose-limiting toxicities of other ADC platforms such as severe neutropenia, neuropathy and ocular toxicity. These are encouraging signals as we look forward to reporting more mature data in the second half of the year and continuing to advance XMT-1536 for both platinum-resistant ovarian cancer and NSCLC adenocarcinoma patients."

The expansion portion of the Phase 1 study is enrolling patients with platinum-resistant ovarian cancer, fallopian tube or primary peritoneal cancer who have received up to three lines of prior therapy and in some cases four lines of prior therapy regardless of platinum status as well as patients with NSCLC adenocarcinoma who had received prior treatment with platinum-based therapy and immunotherapy or targeted agents. With a data cutoff of May 1, 2020 these data include 34 patients total, 27 with ovarian cancer and seven with NSCLC adenocarcinoma. Patients with ovarian cancer had a median of three prior lines of treatment (range 1-5), and patients with NSCLC adenocarcinoma had a median of two lines of therapy (range 1-3). Fifteen of the patients were dosed at 36 mg/m2, and 19 patients were dosed at 43 mg/m2 every four weeks. Key findings include:

·Safety profile consistent with previously reported dose escalation data and no new safety signals observed.
oThe most frequently (≥20%) reported treatment-related adverse events (TRAEs) were Grade 1-2 fatigue, nausea, vomiting, pyrexia, decreased appetite, diarrhea and fever and transient AST elevation without associated changes in bilirubin or cases of Hy’s law.
oThere were no reported cases of severe neutropenia, peripheral neuropathy or ocular toxicity.

·Promising antitumor activity observed in platinum-resistant ovarian cancer.
oOf the 20 patients that were evaluable for response, 2/20 (10%) achieved confirmed complete responses (CRs) and 5/20 (25%) achieved confirmed partial responses (PRs) for an objective response rate (ORR) of 35%. Additionally, 1/20 (5%) patients achieved an unconfirmed partial response for which a confirmatory scan was pending at the time of the data cutoff, and 8/20 (40%) patients achieved stable disease (SD); the disease control rate (DCR) was 16/20 (80%).
o The majority of responders had prior treatment with bevacizumab, PARP inhibitors, or both. Both patients with confirmed complete responses had prior treatment with bevacizumab and PARP inhibitors.

·Data continue to support a NaPi2b biomarker-based patient selection strategy.
oAn emerging biomarker-response relationship continues to be observed. For consistency, these data were bifurcated using the same expression level as used in the dose escalation portion of the study. More data are needed to define the patient selection strategy.
§Among those patients with higher NaPi2b expression, two (2/14) patients achieved a CR, and two (2/14) achieved a PR.
§Two (2/2) patients with NaPi2b expression not yet determined at the time of data cutoff achieved confirmed PRs.
§One (1/4) patient with lower NaPi2b expression (H-score of 90) achieved a confirmed PR.
§The Company expects to define the patient selection strategy based on the total data set from patients treated with XMT-1536.

Response – Ovarian Cancer N=20* All Higher
NaPi2b o Lower
NaPi2b oo NaPi2b
Not Yet
Determined
N 20 14 4 2
CR 2 (10%) 2 (14%) 0 (0%) 0 (0%)
PR 5 (25%) 2 (14%) 1 (25%) 2 (100%)
uPR** 1 (5%) 1 (7%) 0 (0%) 0 (0%)
SD 8 (40%) 7 (50%) 1 (25%) 0 (0%)
PD 4 (20%) 2 (14%) 2 (50%) 0 (0%)

*7 patients not evaluable: 1 withdrew consent (Lower NaPi2b Expression); 1 with unrelated SAE leading to discontinuation and death (Lower NaPi2b Expression); 5 have not yet received a scan

**uPR=1 patient with unconfirmed PR; confirmatory scan pending at the time of data cut

O Higher NaPi2b Expression: defined in dose escalation as at / above lowest H-score at which response observed (≥110)

OO Lower NaPi2b Expression: defined in dose escalation as below the lowest H-score at which response observed (<110)

·More data are needed to assess antitumor activity of XMT-1536 in NSCLC adenocarcinoma patients.
oAt the time of data cutoff, four out of seven NSCLC adenocarcinoma patients were evaluable for response, and 2/4 (50%) patients had achieved SD as best response.

Conference Call Details

Mersana Therapeutics will host a conference call and webcast today at 8:00 a.m. ET during which investigator Debra L. Richardson, MD, Associate Professor of Gynecologic Oncology at the Stephenson Cancer Center at the University of Oklahoma Health Sciences Center and the Sarah Cannon Research Institute and members of the Mersana executive team will present and discuss these data. To access the call, please dial 877-303-9226 (domestic) or 409-981-0870 (international) and provide the Conference ID 7785868. A live webcast of the presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com.

On May 27, 2020 Fresenius Kabi reported that the U.S. Food and Drug Administration (FDA) has accepted for review the company`s Biologics License Application (BLA) for MSB11455, a biosimilar candidate of Neulasta (pegfilgrastim)* (Press release, Fresenius, MAY 27, 2020, View Source [SID1234558523]). This is an important achievement in the development of Fresenius Kabi’s biosimilar pipeline in the US. Fresenius Kabi also received acceptance for review of its regulatory submission for its pegfilgrastim biosimilar candidate from the European Medicines Agency this month. (* Neulasta is a registered trademark of Amgen)

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On May 27, 2020 Axial Biotherapeutics, a biotechnology company dedicated to building a unique class of gut-targeted programs for neurodegenerative diseases and neurodevelopmental disorders, reported that the David H. Donabedian, Ph.D., Co-founder and Chief Executive Officer of Axial Biotherapeutics will present a company overview at the Jefferies Virtual Global Healthcare Conference on Wednesday, June 3, 2020 at 4:30 PM ET (Press release, Axial Biotherapeutics, MAY 27, 2020, View Source [SID1234558522]).

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On May 27, 2020 GlaxoSmithKline (GSK) plc reported new data from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical programme, which further highlight the potential of the investigational anti-BCMA (antibody drug conjugate against B-cell maturation antigen) agent belantamab mafodotin for relapsed/refractory multiple myeloma both as a monotherapy and in combination (Press release, GlaxoSmithKline, MAY 27, 2020, View Source [SID1234558521]). The data are being presented at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting.

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In the 13-month follow-up data from the DREAMM-2 study (abstract #8536), treatment with single-agent belantamab mafodotin, administered as a 2.5 mg/kg dose every three weeks (Q3W), showed a median duration of response (DoR) of 11 months (95% CI, 4.2–not reached) and a median overall survival (OS) of 14.9 months (95% CI, 9.9–not reached) in a heavily pre-treated patient population who received a median of seven prior lines of treatment and were refractory to an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody. The overall response rate (ORR) was consistent with the six-month data at 32% (31 out of 97 patients). Of these patients, the majority (58%) had a very good partial response or greater, including two stringent complete responses and five complete responses. The proportion of patients achieving clinical benefit (minimal response or better) was 36% (95% CI, 26.6–46.5).

Dr Axel Hoos, Senior Vice President and Head of Oncology R&D, GSK said: "The updated results from the DREAMM-2 study being presented at ASCO (Free ASCO Whitepaper) further demonstrate the potential of belantamab mafodotin to help address a significant unmet need for patients whose multiple myeloma continues to progress despite available treatment options. We are encouraged by these data as we work to bring belantamab mafodotin to patients suffering from this aggressive disease."

No new safety signals were identified with longer term follow-up with belantamab mafodotin. The most commonly reported grade 3 or higher adverse events (occurring in more than 10% of patients) in patients receiving the 2.5 mg/kg dose were keratopathy/microcyst-like epithelial changes (MECs) (46%), thrombocytopenia (22%), anaemia (21%), lymphocyte count decreased (13%) and neutropenia (11%). The first event of keratopathy (MECs) – characterised as changes in the corneal epithelium as seen on eye examination which can manifest with or without symptoms – had resolved in 77% of patients in the 2.5 mg/kg arm at time of data cut-off and no permanent loss of vision has been reported to date.

Belantamab mafodotin is not currently approved for use anywhere in the world.

Dr Sagar Lonial, Chief Medical Officer of the Winship Cancer Institute of Emory University and principal investigator of the DREAMM-2 study said: "Despite our best efforts, a significant number of patients will relapse following treatment with an immunomodulatory drug, proteasome inhibitor and an anti-CD38 antibody. For this reason, we need novel therapies that not only induce responses, but maintain them as long as possible. These latest results from DREAMM-2 continue to reinforce that belantamab mafodotin has the potential to be an important treatment option for patients whose disease continues to progress despite currently available therapies."

The DREAMM-2 study serves as the basis for the belantamab mafodotin Biologics License Application and Marketing Authorisation Application, which are currently under review by the US Food and Drug Administration and European Medicines Agency, respectively.

Initial results from the DREAMM-6 study (abstract #8502) examining belantamab mafodotin in combination with bortezomib/dexamethasone (BorDex) in patients whose disease has become refractory or relapsed after one or more prior lines of treatment are also being presented at ASCO (Free ASCO Whitepaper). In this analysis, belantamab mafodotin 2.5 mg/kg Q3W plus BorDex (B-Vd) resulted in an ORR of 78% (14 out of 18 patients), with 50% achieving a very good partial response and 28% achieving a partial response (95% CI, 52.4–93.6). The proportion of patients achieving clinical benefit (minimal response or better) was 83% (95% CI 58.6–96.4). The median DoR has not yet been reached at a median of 18.2 weeks on treatment.

Grade 3 or greater adverse events included keratopathy (MECs) (56%) and thrombocytopenia (61%). There were no cases of grade 4 keratopathy (MECs).

Hoos added: "We are encouraged by these initial results from the DREAMM-6 study showing the potential of combination therapy with belantamab mafodotin in patients with earlier stages of multiple myeloma and look forward to sharing the full data once it is available."

About DREAMM-2
DREAMM-2 is an open label study of belantamab mafodotin. Patients in the trial had actively progressing multiple myeloma that had worsened despite current standard of care and were randomised to two arms to receive either 2.5 mg/kg or 3.4 mg/kg belantamab mafodotin Q3W. Overall, patients in DREAMM-2 had more advanced disease, poorer prognosis and performance status and also had a greater number of prior lines of therapy in comparison with patients in DREAMM-1, the first time in human study of belantamab mafodotin.

About DREAMM-6
DREAMM-6 is an open label phase I/II study evaluating the safety, tolerability and efficacy of belantamab mafodotin when administered in combination with approved regimens of either lenalidomide plus dexamethasone (Len/Dex; Arm A) or Bor/Dex (Arm B) in patients with RRMM who have become refractory or relapsed after one or more prior lines of treatment. Part 1 of the study is a dose escalation phase to evaluate the safety and tolerability of up to three dose levels and up to two dosing schedules of belantamab mafodotin in combination Len/Dex or Bor/Dex. Part 2 will further evaluate the safety and preliminary clinical activity of belantamab mafodotin at selected dose levels and dosing schedules in combination with Len/Dex or Bor/Dex.

About multiple myeloma
Multiple myeloma is the third most common blood cancer and is generally considered treatable, but not curable.[1] Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.[2]

About B-cell maturation antigen (BCMA)
The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway has been shown to be important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients and BCMA membrane expression is universally detected in myeloma cell lines.[3]

About belantamab mafodotin (GSK2857916)
Belantamab mafodotin is an investigational antibody drug conjugate comprising a humanised anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker.[4] The drug linker technology is licensed from Seattle Genetics; monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa.

Trial Name

GSK ID/NCT ID

Status

Design

DREAMM-1

117159/ NCT02064387

Completed

A Phase I Open-label Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma and Other Advanced Hematologic Malignancies Expressing BCMA

DREAMM-2

205678/ NCT03525678

Active, not recruiting

A Phase II Study to Investigate the Efficacy and Safety of Two Doses of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma Who are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed Prior Treatment with an Anti-CD38 Antibody

DREAMM-3

207495/ NCT04162210

Recruiting

A Phase III Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) Compared to Pomalidomide plus low-dose Dexamethasone (Pom/Dex) in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-4

205207/ NCT03848845

Recruiting

A Phase I/II Single Arm Open-Label Study to Explore Safety and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pembrolizumab in Subjects with Relapsed/Refractory Multiple Myeloma

DREAMM-5

208887/

NCT04126200

Recruiting

A Phase I/II, Randomized, Open-label Platform Study of Belantamab Mafodotin (GSK2857916) with Innovative Combination Anti-Cancer Treatments in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-6

207497/ NCT03544281

Recruiting

A Phase I/II Randomized Study to Evaluate Safety, Tolerability and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Lenalidomide plus Dexamethasone (Arm A), or in Combination with Bortezomib plus Dexamethasone (Arm B) in Subjects with Relapsed/Refractory Multiple Myeloma

DREAMM-7

207503/

NCT04246047

Recruiting

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Dexamethasone versus Daratumumab, Bortezomib, and Dexamethasone in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-8

207499

Planned

A Phase III, Multicentre, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) in Combination with Pomalidomide plus Low-Dose Dexamethasone (BPd) versus Pomalidomide plus Bortezomib and Low-Dose Dexamethasone (PVd) in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-9

209664/ NCT04091126

Recruiting

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Lenalidomide and Low-Dose Dexamethasone (VRd) vs. VRd in Participants with Newly Diagnosed Multiple Myeloma who are Ineligible for Transplant

DREAMM-10

207500

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with a Novel Agent versus SoC

ISS/GSK Co-Sponsored Study

209418/ NCT03715478

Recruiting

A Phase I/II Dose-escalation and Dose-expansion Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pomalidomide plus Low-dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma Who Have Received Two or More Prior Lines of Therapy That Must Have Included Lenalidomide and a Proteasome Inhibitor

GSK in Oncology

GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics, and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On May 27, 2020 Novartis reported a new exploratory subgroup analysis of the Phase III MONALEESA-3 and MONALEESA-7 trials, to be presented during the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program, reinforcing the overall survival (OS) benefit of Kisqali (ribociclib) (Press release, Novartis, MAY 27, 2020, View Source [SID1234558518]). In this subgroup analysis, Kisqali plus endocrine therapy increased OS compared to endocrine therapy alone among women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer with visceral metastases, consistent with the benefit seen in the overall study populations.

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"The analysis, looking across two Phase III trials, supports the use of Kisqali in the first-line setting regardless of menopausal status or metastatic location," said Denise Yardley, MD, Principal Investigator, Sarah Cannon Research Institute. "Patients with visceral metastases generally face worse prognosis and a higher risk for treatment resistance, so the consistent overall survival results with Kisqali combination therapy for these patients is compelling."

In the MONALEESA trials, where Kisqali was studied in premenopausal women in combination with NSAI plus goserelin (MONALEESA-7) and in postmenopausal women in combination with fulvestrant (MONALEESA-3), approximately 60% of the participants had visceral metastases (excluding visceral crisis), reflective of real-world clinical practice. In these patients, Kisqali in combination with endocrine therapy showed a 30% reduction in the risk of death in MONALEESA-7 [median OS of not evaluable (NE) vs. 39.9 months with NSAI plus goserelin; HR= 0.698 (95% CI: 0.462-1.054)] and a 20% reduction in the risk of death in MONALEESA-3 [median OS of 41.0 vs. 39.4 months with fulvestrant; HR=0.804 (95% CI: 0.596-1.083)].

In patients with liver metastases, Kisqali combination therapy showed a 47% reduction in the risk of death in MONALEESA-7 [median OS of NE vs. 33.6 months with NSAI plus goserelin; HR=0.531 (95% CI: 0.321-0.877)] and a 37% reduction in the risk of death in MONALEESA-3 [median OS of 36.1 vs. 24.1 months with fulvestrant; HR=0.629 (95%CI: 0.421-0.942)]. The adverse events were consistent with the overall populations.

"Superior overall survival with Kisqali is proven in two phase III trials, and this subgroup analysis shows that Kisqali could make a difference in survival even among patients with the most aggressive forms of advanced breast cancer," said Susanne Schaffert, PhD, President, Novartis Oncology. "Patients are the inspiration behind everything we do, and we will continue to pursue bold treatment advancements that help reimagine the future for people with cancer in hopes that they can live longer, and better."

Additional Kisqali data presented during the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program include:

An oral presentation on the largest pooled biomarker dataset of any CDK4/6 inhibitor in advanced breast cancer to date across a targeted panel of approximately 550 genes related to cancer and signaling pathways. The analysis identifies key potential gene alterations and their associations with response or resistance to Kisqali across all three MONALEESA trials4.
Updated results from CompLEEment-1, a Phase IIIb single-arm trial of 3,246 patients in first-line setting evaluating Kisqali plus letrozole in an expanded and diverse population closely resembling real-world clinical practice. Results were consistent with those observed in the MONALEESA trials, including median time to progression 27.1 months (95% CI: 25.7-NE) and overall response rate 43.6% (95% CI: 41.5-45.8%). The most common AEs were neutropenia, nausea and fatigue. Treatment-related AEs led to discontinuation in 12.9% of patients5.
A retrospective study using real-world data assessing the economic burden of neutropenia, the most common adverse event following administration of CDK4/6 inhibitors. Neutropenia was reported in 38 patients (25%) in the palbociclib group and 25 patients (17%) in the Kisqali group. Similar rates of neutropenia were observed for grades 1/2 and 4, however, a numerical difference was observed for grade 3: palbociclib 35% vs. Kisqali 26%6.
Visit View Source for the latest information from Novartis, including our commitment to the Oncology community, and access to our ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program data presentations (for registered participants).

Kisqali is approved for use in more than 75 countries around the world, including the United States and European Union member states. Kisqali has shown statistically significant overall survival benefit in two Phase III trials with two distinct patient populations7,8.

About Kisqali (ribociclib)
Kisqali is the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent and sustained efficacy compared to endocrine therapy alone. Overall survival results from MONALEESA-7 and MONALEESA-3 were presented at ASCO (Free ASCO Whitepaper) 2019 and ESMO (Free ESMO Whitepaper) 2019 respectively, demonstrating Kisqali plus endocrine therapy significantly extends life in pre/perimenopausal or postmenopausal women with HR+/HER2- advanced breast cancer. Overall survival follow-up is ongoing for the Phase III MONALEESA-2 trial.

Kisqali was initially approved by the US Food and Drug Administration (FDA) in March 2017 and by the European Commission (EC) 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 in combination with an aromatase inhibitor was approved for the treatment of pre-, peri- or postmenopausal women as initial endocrine based therapy, and also indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women by the FDA in July 2018 and by the EC in December 2018. Regulatory filings are underway with other health authorities worldwide.

Novartis is continuing to reimagine cancer by investigating Kisqali in early breast cancer. The NATALEE study is a Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO).

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

About Novartis in Advanced Breast Cancer
Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. We’ve taken a bold approach to our research by including patient populations often neglected in clinical trials, identifying new pathways or mutations that may play a role in disease progression and developing therapies that not only maintain, but also improve, quality of life for patients. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with advanced breast cancer.

Indication
KISQALI (ribociclib) is a prescription medicine used in combination with an aromatase inhibitor for the treatment of pre/perimenopausal or postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer, as initial endocrine-based therapy; or fulvestrant for the treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer, as initial endocrine-based therapy or following disease progression on endocrine therapy.

Important Safety Information
KISQALI can cause severe or life-threatening inflammation of the lungs. Patients should tell their health care provider right away if they experience breathing problems or chest pains. KISQALI can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. KISQALI is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. KISQALI can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking KISQALI and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills.

Before taking KISQALI, patients should tell their health care provider if they are pregnant, or plan to become pregnant as KISQALI can harm an unborn baby. Females who are able to become pregnant and who take KISQALI should use effective birth control during treatment and for at least 3 weeks after the last dose of KISQALI. Do not breastfeed during treatment with KISQALI and for at least 3 weeks after the last dose of KISQALI.

Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with KISQALI. Patients should avoid grapefruit or grapefruit juice while taking KISQALI.

The most common side effects (incidence ≥20%) include white blood cell count decreases, nausea, infections, tiredness, diarrhea, vomiting, hair loss, headache, constipation, rash, and cough. The most common grade 3/4 side effects (incidence >5%) were low neutrophils, low leukocytes, abnormal liver function tests, and low lymphocytes. Abnormalities were observed in hematology and clinical chemistry laboratory tests.