On December 10, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for malignancies, reported that it has released the follow-up safety and efficacy data of the company’s investigational Bcl-2 selective inhibitor, lisaftoclax (APG-2575), in combination with azacitidine (AZA) for the treatment of patients with myelodysplastic syndrome (MDS), in a Poster Presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in San Diego, CA, the United States (Press release, Ascentage Pharma, DEC 10, 2024, View Source;ascentage-pharma-releases-updated-data-of-bcl-2-inhibitor-lisaftoclax-in-mds-that-demonstrates-potential-clinical-benefits-and-favorable-safety-302327621.html [SID1234649006]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The ASH (Free ASH Whitepaper) Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, results from multiple clinical and preclinical studies on four of Ascentage Pharma’s drug candidates (olverembatinib, lisaftoclax, APG-2449, and APG-5918) have been selected for presentations, including two Oral Reports, at this year’s ASH (Free ASH Whitepaper) Annual Meeting.

Thes data underscored the potential clinical benefit and manageable safety of lisaftoclax in combination with AZA in MDS. In the results, the combination regimen demonstrated an overall response rate (ORR) of 75% in patients with treatment-naïve (TN) or relapsed/refractory (R/R) MDS, and no patient withdrew from the study due to intolerable toxicities.

Prof. Jie Jin, the principal investigator of the study from the First Affiliated Hospital, Zhejiang University School of Medicine, noted, "For a long time, there has not been much progress in the treatment of higher-risk MDS and the outcome of the current standard treatment with hypomethylating agents has been disappointing. In patients with MDS, the investigational novel Bcl-2 inhibitor lisaftoclax in combination with AZA has demonstrated clinical benefit and manageable safety that support continued treatment. These observations suggest that the regimen can potentially offer a new standard treatment in MDS."

Prof. Huafeng Wang, the presenter of this study from the First Affiliated Hospital, Zhejiang University School of Medicine, commented, "Patients with higher-risk MDS often have inadequate marrow function and low tolerance for therapeutic agents. The investigational novel Bcl-2 inhibitor lisaftoclax in combination with AZA has shown encouraging clinical benefit, manageable safety, and low suppression on bone marrow function. More importantly, the regimen showed a low rate of treatment-related infections that were mostly mild, and a low rate of mortalities in early treatment, thus overcoming some of the biggest clinical challenges in this patient population."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "These updated efficacy and safety data of lisaftoclax in combination with AZA are very encouraging as they reaffirmed the therapeutic potential of this novel drug candidate. A global registrational Phase III study of lisaftoclax in combination with AZA for the first-line treatment of MDS is currently ongoing and an NDA for lisaftoclax in R/R chronic lymphocytic leukemia/small lymphocytic lymphoma has already been accepted and granted the Priority Review designation in China. Fulfilling our founding mission of addressing unmet clinical needs in China and around the world, we will expedite the global clinical development of our key drug candidates to bring more safe and effective therapies to patients as soon as possible."

Highlights of the data this study reported at ASH (Free ASH Whitepaper) 2024 are as below:

Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor, in Combination with Azacitidine in Treatment of Patients with Myelodysplastic Syndrome (MDS)
Format: Poster Presentation
Abstract#: 3202
Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster II

Highlights:

Background: Hypomethylating agents (HMAs) remain the standard of care in higher-risk MDS. However, its clinical efficacy is limited, and patients who have failed or are resistant to HMAs have a poor prognosis, leaving them in need of new therapeutic options.

Introduction: Preclinical data have shown that novel investigational Bcl-2 inhibitor lisaftoclax combined with an HMA can synergistically induce apoptosis in cancer cells in AML and MDS. Reported here are the follow-up safety and efficacy data from a Phase Ib/II clinical trial evaluating lisaftoclax combined with azacitidine in adults (≥18 years) with MDS.

Enrolled Patients and Study Methods:

This study enrolled patients with higher-risk MDS (IPSS-R score > 3.5; blasts > 5%), including those with TN or R/R disease. Lisaftoclax at an assigned dose (400, 600, or 800 mg) was administered orally once daily from Days 1 to 14 and combined with azacitidine (75 mg/m2/day) on Days 1 to 7 in repeated 28-day cycles. A daily ramp-up was used before the first cycle to prevent TLS. The primary objectives of the study were to assess the efficacy and safety of the combination regimen in patients with MDS and establish the recommended Phase III dose for lisaftoclax. Complete response (CR) and marrow CR (mCR) rates were evaluated in accordance with 2006 International Working Group (IWG) criteria.
As of July 1, 2024, 49 patients were enrolled: 8 had R/R MDS (lisaftoclax 600 mg [n=5] and 800 mg [n=3]) and 41 had TN MDS (lisaftoclax 400 mg [n=16], 600 mg [n=23], and 800 mg [n=2]). The median (range) age was 66 (22-83) years, and 55.1% of patients were male. IPSS-R risk categories were intermediate (12/49 [24.5%]), high (24/49 [49.0%]), and very high (13/49 [26.5%]). Among the 39 patients with genetic mutational profile data, 9 (23.1%) had TP53 mutations; 11 (28.2%) had TET2 mutations; 10 (25.6%) had ASXL1 mutations; and 10 (25.6%) had RUNX1 mutations. At baseline, 70.8% of patients reported grade ≥ 3 anemia; 54.2% had grade ≥ 3 neutropenia; and 45.8% had grade ≥ 3 thrombocytopenia.
Efficacy Results: In 8 patients with R/R MDS, the median (range) duration of treatment (DOT) was 3.2 (1.2-9.4) months. The ORR (CR[12.5%]+marrow CR[62.5%]) was 75.0% (95% CI, 34.9-96.8). In 40 efficacy-evaluable patients with TN MDS, the median DOT (range) was 4.5 (0.5-12.1) months; the ORR was 77.5% (95% CI, 61.5-89.2); and the CR rate was 25.0% per IWG 2006 criteria. Furthermore, the ORR and CR rate in 23 patients with TN MDS treated with lisaftoclax 600 mg combined with azacitidine were 73.9% and 30.4%, respectively; because these patients had a relatively longer median DOT (6.01 months), we conducted further analyses per IWG 2023 criteria. The composite CR rate (CR2023 = CR [52.2%] + CRL [17.4%]) was 69.6%, and the median time to CR (range) was 2.84 (1.1-8.7) months. Both the median progression-free survival and overall survival rates were not reached.

Safety Results:

Grade ≥ 3 infections were reported in 46.9% of patients, of which 26.5% were treatment related. Treatment delays between cycles due to AEs occurred in 11 (22.4%) patients, with a median delay time (range) of 12 (1-63) days.
A total of 95.9% of patients reported TRAEs, of which 87.8% were grade ≥ 3 AEs and 28.6% were serious AEs. Common grade ≥ 3 hematologic TRAEs included leukocyte count decreased (71.4%), neutropenia (65.3%), thrombocytopenia (65.3%), anemia (20.4%), and febrile neutropenia (12.2%).
Neither 60-day mortality nor TLS was reported.
Conclusions: The clinical data support an emerging role for lisaftoclax in combination with azacitidine for treatment of patients with higher-risk TN or R/R MDS. The combination therapy was efficacious and well tolerated, resulting in no 60-day mortality, few dose modifications, and low infection rates, supporting further clinical development of this combination in patients with higher-risk MDS.

On December 10, 2024 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported that it has dosed the first patient in the IDEAYA-sponsored Phase 1 trial evaluating the combination of IDE161, the company’s investigational, potential first-in-class, small molecule poly (ADP-ribose) glycohydrolase, or PARG, inhibitor, in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in endometrial cancer patients with high microsatellite instability (MSI-high) and microsatellite stable(MSS) (Press release, Ideaya Biosciences, DEC 10, 2024, View Source [SID1234649005]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We continue to progress our IDE161 program and are excited to have the first patient dosed evaluating IDE161 in combination with KEYTRUDA in MSI-high and MSS endometrial cancer patients. This trial is part of our overall IDE161 clinical combination strategy that is focused on high conviction rational combinations," commented Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

"We are continually looking for ways to improve outcomes for patients with MSI-high and MSS endometrial cancer, and PARG has shown promising potential as a precision oncology target in these settings. IDE161 has shown robust anti-tumor activity in preclinical models, and I look forward to evaluating IDE161’s impact on endometrial cancer patients in combination with KEYTRUDA," added Dr. Panos Konstantinopoulos, M.D., Ph.D., Director of Translational Research and attending oncologist in the Division of Gynecologic Oncology at Dana-Farber Cancer Institute, and an Associate Professor of Medicine at Harvard Medical School.

IDE161 is a potential first-in-class inhibitor of poly(ADP-ribose) glycohydrolase (PARG), a novel, mechanistically distinct target in the same clinically validated biological pathway as poly(ADP-ribose) polymerase (PARP). IDE161 has been granted two FDA Fast Track designations in platinum-resistant advanced or metastatic ovarian cancer patients having tumors with BRCA1/2 mutations, and in pretreated advanced or metastatic HR+, Her2-, BRACA1/2 mutant breast cancer.

Under the clinical trial collaboration and supply agreement, Merck will provide KEYTRUDA to IDEAYA, the sponsor of the Phase 1 clinical combination trial. IDEAYA and Merck each retain all commercial rights to their respective compounds, including as monotherapy or as combination therapies.

The safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE161 in combination with KEYTRUDA is being evaluated as an arm in IDE161-001 (NCT05787587), an IDEAYA-sponsored Phase 1 trial of IDE161 in solid tumors. The selection of an initial Phase 1/2 monotherapy expansion dose has been made in a priority tumor type based on adverse event (AE) profile and preliminary clinical efficacy observed.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On December 10, 2024 TransThera Sciences (Nanjing), Inc. (the "TransThera"), a clinical demand-oriented, registrational clinical stage biopharmaceutical company focusing on discovering and developing innovative small molecule therapies for oncology, inflammatory and cardiometabolic diseases, reported the poster presentation at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to discuss the phase I study results of TT-01488, a novel reversible BTK inhibitor for patients with relapsed or refractory B-cell malignancies (Press release, TransThera Biosciences, DEC 10, 2024, View Source;in-patients-with-relapsed-or-refractory-b-cell-malignancies-302326854.html [SID1234649004]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Bruton’s tyrosine kinase (BTK) plays a critical role in the B-cell receptor signaling pathway, functioning as an important regulator of cell proliferation and cell survival in various B-cell malignancies. Currently there are 5 approved irreversible BTK inhibitors (BTKis) in the world. Due to the emergence of acquired mutation in the inhibitor’s covalent binding site (C481S), there is a high unmet medical need to develop next-generation BTKi to overcome the resistance.

TT-01488 is a next-generation, non-covalent, reversible BTKi which can overcome the acquired resistance to irreversible BTKis. In the preclinical study, TT-01488 potently Inhibits both wildtype and C481S-mutant BTK.

The Phase I study of TT-01488 presented at ASH (Free ASH Whitepaper) Annual Meeting was an open, multi-center, dose escalation study. As of the data cut-off date on October 2, 2024, 18 patients with pre-treated B-cell malignancies were enrolled, with the median 3 lines of prior therapies. TT-01488 was well-tolerated in all patients. Neither dose limiting toxicity (DLT) occurred nor any bleeding, atrial flutter or atrial fibrillation was reported. In pharmacokinetics and pharmacodynamics study, sustained pBTK C481S-mutant inhibition covering IC­90 was observed at steady state following multiple dosing at both 150 mg (QD) and 100 mg (BID) dose levels. Among 14 efficacy evaluable patients, objective response rate (ORR) was 57% (8/14)，including 3 complete remission (CR) and 5 partial remission (PR). 100% (7/7) of ORR was achieved in mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM) and marginal zone lymphoma (MZL). Overall, TT-01488 showed encouraging efficacy in B-cell non-Hodgkin lymphoma (B-NHL) patients, regardless of C481S status and with/without prior cBTKi therapy.

About TT-01488

TT-01488 is an internally developed, non-covalent, reversible BTK inhibitor to overcome acquired resistance developed from marketed covalent BTK inhibitors in various types of relapsed or refractory hematological malignancies. TT-01488 is highly potent against BTK wild type and mutation with high selectivity over EGFR and Tec, indicating its potential for good efficacy and safety.

On December 10, 2024 Pilatus Biosciences Inc. reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to its leading molecule, PLT012, for treating liver and intrahepatic bile duct cancer (HCC/ICCA) (Press release, Pilatus Biosciences, DEC 10, 2024, View Source [SID1234649003]). Achieved in November 2024, this designation marks a crucial advancement in developing innovative therapies for patients facing these challenging cancers. Dr. Raven Lin, CEO, emphasized the company’s commitment to addressing urgent medical needs, while Prof. Ping-Chih Ho highlighted PLT012’s unique therapeutic approach targeting the tumor microenvironment. Pilatus is actively working with regulatory authorities to expedite PLT012’s development and availability.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Pilatus Biosciences, a preclinical-stage biopharmaceutical company spun out from the Ludwig Institute for Cancer Research (Lausanne), is leading the development of first-in-class biologics targeting metabolic checkpoints. Supported by the Cancer Research Institute (New York), the company employs a pioneering approach to immunometabolism, reprogramming the immune microenvironment to combat cancer effectively.

"We are honored to receive Orphan Drug Designation for PLT012, a milestone that reflects our dedication to addressing the urgent need for innovative therapies in liver and intrahepatic bile duct cancer," said Dr. Raven Lin, CEO and Co-founder of Pilatus Biosciences. Prof. Ping-Chih Ho, Chair of the Scientific Advisory Board and Co-founder of Pilatus Biosciences, added, "PLT012 leverages metabolic checkpoint targeting to reprogram the tumor microenvironment (TME), offering a unique therapeutic approach. This designation highlights the promising scientific discoveries and results we have achieved in addressing the underserved area. It further motivates us to accelerate PLT012’s development and collaborate globally to bring this promising treatment to patients with limited options."

Currently, Pilatus Biosciences is advancing the development of PLT012, actively engaging with regulatory authorities and stakeholders to expedite the availability of this promising therapy.

About PLT012

PLT012, is a humanized anti-CD36 antibody with a unique dual mechanism of action (MOA): it simultaneously disarms immunosuppressive cell populations and amplifies effector T cell functions. PLT012 has shown potential against multiple tumors with unmet medical needs. It is set to advance to its first U.S. IND submission and first patient dosing in 2025. As a monotherapy, PLT012 demonstrates remarkable anti-tumor efficacy in both immune ‘hot’ and ‘cold’ tumor models with a significant augmentation in GzmB-expressing CD8+ T cells and reductions in both intratumoral Tregs and pro-tumorigenic macrophage. Additionally, PLT012 treatment alters the exhaustion features of cytotoxic CD8+ T cells by increasing the populations of progenitor- (Texprog) and tumoricidal activities in terminal-exhausted T cells (Texterm), highlighting enhanced anti-tumor immunity when combined with immune checkpoint blockade therapies, such as PD-1 or PD-L1 inhibitors.

About Orphan Drug Designation

The FDA’s Orphan Drug Designation (ODD) program provides orphan status to drugs defined as those intended for the treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the United States. ODD qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions and 7 years marketing exclusivity upon FDA approval.

About Liver and Intrahepatic Bile Duct Cancer (HCC/ICCA)

Primary liver cancer first occurs in either the liver or the intrahepatic bile ducts. The two most common types of liver and intrahepatic bile duct cancer are hepatocellular carcinoma (HCC, 80-90% of cases), and intrahepatic cholangiocarcinoma (ICCA, 10-15% of cases). In HCC and ICCA, metabolic reprogramming plays a crucial role in promoting tumor progression by modifying the TME to support tumor growth and immune evasion.

For HCC, the most common first-line systemic therapies include either a combination of a PD-L1 inhibitor and a VEGF inhibitor or a combination of a PD-L1 inhibitor and a CTLA-4 inhibitor. Most patients will require multiple lines of treatment, as the recurrence rate of HCC has been reported to be as high as 88%. Second-line treatments for HCC are primarily multiple tyrosine kinase receptor inhibitors, even the incidence of a second HCC recurrence is 50%-70%. Additional lines of treatment may be administered if the patient can tolerate a second-line therapy with a different MOA than those previously administered.

PLT012 emerges as a promising candidate, demonstrating dual MOA that synergizes with existing treatments and provide immune-stimulating effects in the TME, potentially enhancing therapeutic outcomes.

On December 10, 2024 Novartis reported results from an updated analysis of the pivotal Phase III NATALEE trial of Kisqali (ribociclib) that underscore the extended efficacy beyond the duration of treatment in combination with endocrine therapy (ET) (Press release, Novartis, DEC 10, 2024, View Source [SID1234649002]). Results showed a sustained reduction in distant recurrence of 28.5% (HR=0.715; 95% CI 0.604-0.847; nominal P<0.0001), compared to ET alone, in patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC)1.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Reduction in distant recurrence, known as distant disease-free survival (DDFS), is a decrease in the rate of cancer returning and spreading to other organs. The DDFS with Kisqali was consistent across all pre-specified patient subgroups, including those with node-negative (N0) disease1. These late-breaking data are being presented at the 2024 San Antonio Breast Cancer Symposium (SABCS).

"In day-to-day practice, we see a real and persistent risk of breast cancer coming back after early diagnosis, often as metastatic disease," said Paolo Tarantino, M.D., Advanced Fellow at Dana-Farber Cancer Institute and Harvard Medical School. "The latest NATALEE and real-world data presented at SABCS reaffirm we can better address risk of recurrence for all patients at high-risk, including selected patients with node-negative disease, by offering them adjuvant CDK4/6 inhibitor treatment in addition to endocrine therapy."

DDFS results across pre-specified subgroups1,4**:

Subgroup Hazard Ratio 95% CI
Intention-To-Treat Population 0.715 0.604-0.847
AJCC Tumor Stage IIA 0.396 0.218-0.720
AJCC Tumor Stage IIB 0.806 0.524-1.238
AJCC Tumor Stage IIIA 0.697 0.524-0.926
AJCC Tumor Stage IIIB 0.569 0.326-0.994
AJCC Tumor Stage IIIC 0.878 0.649-1.188
Node-negative disease 0.696 0.403-1.204
Node-positive disease 0.726 0.608-0.867
Safety remains consistent with previous reports, and no new safety signals were identified5. Adverse events (AEs) of special interest (grade 3 or higher) were neutropenia (44.4%), liver-related AEs (e.g., elevated transaminases) (8.6%), and QT interval prolongation (1.0%)5.

Real-World Risk of Distant Recurrence
Further, real-world evidence presented at the meeting highlights the relatively high incidence of distant recurrences within 5 years despite ET monotherapy for patients at high-risk, regardless of nodal involvement2.

"On the heels of its U.S. FDA and EMA approvals in early breast cancer, it is encouraging to see the continued benefit of adding Kisqali to standard endocrine therapy to help reduce the risk of recurrence," said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. "These data, together with the recent NCCN Guidelines Category 1 preferred treatment recommendation for all eligible patients with early breast cancer, reinforce the opportunity to evolve adjuvant treatment to help a broader group of people."

Additional research presented at the meeting further demonstrates the ongoing focus of Novartis to advance the care of people with breast cancer, including studies investigating the potential of radioligand therapies in the treatment of metastatic breast cancer (MBC)6.

*NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

**The 4-year DDFS analysis was not prespecified and the trial was not powered to demonstrate statistical significance of these results.

About NATALEE
NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali with ET as an investigational adjuvant treatment versus ET alone in patients with stage II and III HR+/HER2- EBC, being conducted in collaboration with TRIO7,8. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable7,8. The primary endpoint of NATALEE is invasive disease-free survival (iDFS) as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria7,8. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial7,8.

About Kisqali (ribociclib)
Kisqali (ribociclib) 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 has been approved as a treatment for breast cancer by regulatory authorities in 99 countries worldwide, including the U.S. FDA and the European Commission9,10. In the US, Kisqali is indicated in combination with an AI as an adjuvant treatment for adults with HR+/HER2- stage II and III early breast cancer at high risk of recurrence, as well as for the treatment of adults with HR+/HER2- advanced or MBC as initial ET; Kisqali is also approved in the metastatic indication in combination with fulvestrant as initial ET or following disease progression on ET in post-menopausal women or in men9. In the EU, Kisqali is approved for the treatment of women with HR+/HER2- advanced or MBC in combination with either an AI or fulvestrant as initial ET or following disease progression10. In pre- or peri-menopausal women, the ET should be combined with a luteinizing hormone-releasing hormone agonist9,10.

In EBC, ribociclib (Kisqali) is the only CDK4/6 inhibitor recommended by the NCCN Guidelines for breast cancer for both all node-positive disease as well as for patients with no nodal involvement with high-risk disease characteristics, such as tumor size >5 cm, or for tumors sized 2-5 cm, either Grade 2 with high genomic risk/Ki-67 ≥20% or Grade 33. In MBC, Kisqali has consistently demonstrated statistically significant overall survival benefit across three Phase III trials11-21. The NCCN Guidelines also recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of people living with HR+/HER2- when combined with an AI3, making Kisqali the preferred first-line treatment of choice for US prescribers in HR+/HER2- MBC.

In addition, Kisqali has achieved the highest score (A) on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) for EBC22; and has the highest rating of any CDK4/6 inhibitor on the ESMO (Free ESMO Whitepaper) Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line pre-menopausal patients with HR+/HER2- advanced breast cancer23. Further, Kisqali in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6 inhibitors, received a score of four out of five for post-menopausal patients with HR+/HER2- advanced breast cancer treated in the first line24.

Kisqali was developed by Novartis under a research collaboration with Astex Pharmaceuticals.

Please see full Prescribing Information for Kisqali, available at www.Kisqali.com