Non-interventional Study to Assess the Effectiveness and Safety of Ribociclib in the Adjuvant Therapy of Hormone Receptor Positive (HR+) HER2-negative Stage II and III Breast Cancer in Real Clinical Practice in Russia

This prospective, observational, multicenter study aims at evaluating the efficacy of adjuvant ribociclib in combination with hormone therapy (aromatase inhibitor ± GnRH aginost) in various subgroups of patients with HR+HER2- stage II-III breast cancer in real clinical practice in Russia. Subgroup division will be based on the tumor grade, lymph node involvement, and the response to test hormone therapy. The study will consist of two cohorts: a prospective one with patients receiving adjuvant therapy with ribociclib combined with Aromatase inhibitors (AI), and a retrospective one with patients receiving adjuvant therapy with AI alone. Thus, both primary data collection and secondary use of data will be organized.

Start Date31 Jul 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

NCT06905301

/ Not yet recruitingNot Applicable

Implementation Study to Describe and Compare Retention Rate and Adherence to Adjuvant Therapy With Ribociclib With and Without Usage of Mobile Application in Patients With HR+ HER2-negative Stage II and III Breast Cancer in Real-world Practice

This study is designed to evaluate the effect of using the application on the adherence of patients with luminal HER2- breast cancer (BC) stage II-III to adjuvant therapy with ribociclib in combination with an aromatase inhibitor (AI). The purpose of the app is to increase adherence to treatment by informing patients about the risks of relapse and adverse event prevention and treatment.

Start Date31 Jul 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

NCT06849947

/ Not yet recruitingPhase 2IIT

Randomized Phase II Trial of Fulvestrant With Ribociclib Versus Physician's Choice Treatments for the Patients Who Recurred After Completion of Adjuvant Cyclin-Dependent Kinase 4/6 Inhibitors in HR+, HER2- Metastatic Breast Cancer as First Line Treatment (CLEE011AKR06R)

▪ Fulvestrant With Ribociclib versus Physician's choice treatments for the patients who recurred after completion of Adjuvant Cyclin-Dependent Kinase 4/6 Inhibitors in HR+, HER2- Metastatic Breast Cancer as first line treatment

Start Date30 Jun 2025

Sponsor / Collaborator

Samsung Medical Center

100 Clinical Results associated with Ribociclib Succinate

100 Translational Medicine associated with Ribociclib Succinate

100 Patents (Medical) associated with Ribociclib Succinate

1,372

Literatures (Medical) associated with Ribociclib Succinate

01 Aug 2025·BREAST

Nationwide real-world practice pattern and clinical data of palbociclib in HR (+), HER2 (−) metastatic breast cancer patients in Korea (KCSG BR21-15)

Article

Author: Kim, Jee Hung ; Kim, Hyun Seon ; Park, In Hae ; Kim, Ji-Yeon ; Koh, Sung Ae ; Lee, Dae-Won ; Hong, Soojung ; Kim, Han Jo ; Baek, Sun Kyung ; Kang, Myoung Joo ; Kim, Seul-Gi ; Kim, Min Hwan ; Won, Hye Sung ; Kim, Gun Min ; Shin, Kabsoo ; Koh, Su-Jin ; Lee, Jieun ; Shin, Seong Hoon ; Park, Yeon Hee ; Jung, Joo Young ; Lee, Kyoung Eun ; Kim, Ju Won ; Im, Seock-Ah ; Woo, In Sook ; Byun, Jae-Ho

BACKGROUND:

Cyclin-dependent kinase (CDK) 4/6 inhibitors have remarkably improved the survival outcome in hormone-receptor-positive (HR+)/human epidermal growth factor-2-negative (HER2-) metastatic breast cancer (mBC). Although PALOMA-2 has met its primary outcome, overall survival (OS) was relatively shorter compared to ribociclib and abemaciclib. In Korea, use of palbociclib + aromatase inhibitor (AI) + gonadotropin-releasing hormone agonist (GnRHa) in premenopausal women is limited, and bilateral salpingo-oophorectomy (BSO) is necessary before treatment. We analyzed the real-world clinical outcome and patient characteristics of letrozole + palbociclib in Korea.

METHODS:

Between August 2016 and December 2022, 1017 HR+/HER2-postmenopausal women treated with first-line letrozole + palbociclib were enrolled. Primary endpoints were real-world progression-free survival (rwPFS) in total population and survival differences according to menopausal status (natural or induced menopause via BSO).

RESULTS:

Patients' median age was 56 (range 27-92) years. Median rwPFS, real-world OS (rwOS) were 28.0 months (95 % confidence interval [CI] 25.5-32.1) and 61.8 months (95 % CI 57.7-70.5), with a median follow-up of 45.1 (IQR, 31.0-56.6) months. BSO group demonstrated similar median rwPFS compared to natural menopause group. Adjuvant tamoxifen ± GnRHa was most frequently prescribed (73.3 %). Primary endocrine resistant mBC patients showed inferior median rwPFS compared to secondary resistant mBC (14.6 vs. 27.1 months, p = 0.0063). Overall response rate was 47.5 %, with a disease control rate of 89.6 %.

CONCLUSION:

This is the largest country-based real-world study on palbociclib + letrozole in Asia. Palbociclib demonstrated median rwOS over 60 months, comparable to other pivotal trials.

01 Jul 2025·BREAST CANCER RESEARCH AND TREATMENT

Non-adherence of cyclin-dependent kinases 4 and 6 inhibitors reduces overall and progression-free survival in patients with hormone receptor–positive breast cancer

Article

Author: LaBorde, Krista ; Trivedi, Meghana V ; Alfartosy, Shahad S ; De La Torre, Rodrigo ; Abughosh, Susan ; Lau, Connie ; Brown, Erika N ; Fatima, Bilqees

PURPOSE:

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy improve survival in patients with hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer (BC). This retrospective study aimed to evaluate CDK4/6i adherence, factors associated with non-adherence, the impact of health-system specialty pharmacy on adherence, and effects of non-adherence on survival outcomes in HR + /HER2- BC patients.

METHODS:

Data was collected from Houston Methodist Hospital System (HM) from HR + /HER2- BC patients with medication fill history utilizing electronic medical records. CDK4/6i adherence was calculated using the mean possession ratio ≥ 80%. Multivariable logistic regression model and Kaplan-Meier analysis were utilized to evaluate factors associated with non-adherence and its impact on survival, respectively.

RESULTS:

A total of 121 patients were assessed and analyzed; 55% patients received abemaciclib, 40% were on palbociclib, and 4% were on ribociclib. More patients were on aromatase inhibitors and tamoxifen (79%) than fulvestrant (21%). Most of the patients were Caucasian (64%), non-Hispanic or Latino (84%), and postmenopausal (66%). Overall, 52 patients (43%) were non-adherent. Patients ≥ 65 years of age (OR: 0.304, [95% CI: 0.110-0.840], P-value: 0.022) and those of Hispanic or Latino ethnicity (OR: 0.291, [95% CI: 0.086-0.985], P-value: 0.047) were more likely to be non-adherent to CDK4/6i. Non-adherence to CDK4/6i was associated with worse overall survival and progression-free survival.

CONCLUSION:

43% patients were non-adherent to CDK4/6i. Older patients and those of Hispanic ethnicity were more likely to be non-adherent. Non-adherent patients had worse survival outcomes, highlighting the unmet need to implement interventions to improve CDK4/6i adherence in these patients.

03 Jun 2025·Expert Review of Anticancer Therapy

CDK4/6 inhibition in early and advanced hormone receptor-positive, HER2-negative breast cancer

Review

Author: Nanda, Rita ; de Oliveira Andrade, Matheus ; Yarlagadda, Sudha

INTRODUCTION:

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition in combination with endocrine therapy is the mainstay of treatment for hormone receptor-positive, HER2-negative (HR + /HER2-) advanced breast cancer; the CDK4/6 inhibitors abemaciclib and ribociclib are also approved for high-risk, early-stage, HR + /HER2- breast cancer. Numerous studies exploring CDK4/6 inhibitors in the early-stage setting are ongoing, as well as many more exploring novel combinations in the metastatic setting.

AREAS COVERED:

Here, we review the basis of CDK4/6 inhibition for HR +/HER2- breast cancer, the pivotal clinical trials which led to regulatory approval, and ongoing trials evaluating novel combinations to further improve outcomes for those with both early and advanced HR+/HER2- breast cancer. Current literature was reviewed by a comprehensive search of PubMed MEDLINE (1/1/2000-12/31/2024).

EXPERT OPINION:

CDK4/6 inhibitors are integral in the management of both advanced and high-risk, early-stage HR + /HER2- breast cancer. Biomarkers predictive of CDK 4/6 inhibitor (CDK4/6i) benefit remain elusive, and clinical and pathological features remain key to identifying those who are candidates for CDK4/6 inhibition in the early-stage setting. Numerous trials evaluating the role of a CDK4/6i with novel endocrine therapy partners and other targeted agents are ongoing, with the goal of improving outcomes for those with HR + /HER2- disease.

361

News (Medical) associated with Ribociclib Succinate

05 Jun 2025

·www.globenewswire.com

Novartis Kisqali® reduces risk of recurrence in younger patients with early breast cancer in NATALEE subgroup analysis

33% reduction in relative risk of invasive disease observed in pre-menopausal early breast cancer (EBC) patients receiving Kisqali in 1-year post-treatment analysis1 Tolerability remained consistent, with fewer treatment discontinuations due to adverse events among pre-menopausal patients1 Rising breast cancer diagnosis rates and more aggressive disease in younger women underscore importance of early detection and care with effective and tolerable treatments that help prevent cancer recurrence2 Separate real-world analysis presented at ASCO demonstrates differences in treatment outcomes that underscore critical need to improve care for Black patients with EBC3 June 1, 2025 – Novartis is announcing data from a new subgroup analysis of the Phase III NATALEE trial evaluating the efficacy and safety of Kisqali® (ribociclib) plus endocrine therapy (ET, a non-steroidal aromatase inhibitor) in patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) at high risk of recurrence across age and menopausal status1. The data will be presented today at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Results at median follow-up of 44.2 months show that patients receiving Kisqali continued to see consistent reductions in risk of recurrence across all efficacy measures, regardless of age and menopausal status1. In this one-year post-treatment analysis, pre-menopausal and younger patients, who often present with more aggressive disease characteristics, experienced greater reductions in risk of recurrence and fewer treatment discontinuations due to adverse events (AEs) than post-menopausal patients1. “As the incidence of early onset breast cancer increases, it is encouraging to see that ribociclib continues to deliver durable risk reduction for a broad population of patients with EBC, including younger patients,” said Dr. Kevin Kalinsky, Division Director of Medical Oncology and Director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University. “Coupled with the lower rates of discontinuation due to AEs seen in this subgroup, these data reinforce the benefit of three-year adjuvant treatment with ribociclib as a well-tolerated intervention for patients seeking to reduce the likelihood of their cancer coming back.” A separate real-world analysis of EBC patients who met the NATALEE trial eligibility criteria and received ET monotherapy found that Black patients were more likely to be younger, pre-menopausal, have stage III tumors, and have more extensive nodal involvement than white patients. After adjusting for these factors, Black patients also had worse RFS, DDFS, and overall survival than their white counterparts. These findings reinforce the critical need to improve care for Black patients with the addition of a CDK4/6 inhibitor to their adjuvant treatment3. Novartis is continuing to add to the body of evidence on the efficacy and safety of Kisqali in different patient populations. Trial design details will be presented at ASCO for the Adjuvant WIDER study, which is enrolling patients that closely reflect the population seen in clinical practice, including more patients from racial and ethnic minority groups4. “There is an undeniable and urgent need to improve outcomes for vulnerable patient populations, including younger and Black patients, who often face more aggressive forms of breast cancer and remain at high risk of recurrence," said Reshema Kemps-Polanco, Executive Vice President and Chief Commercial Officer, Novartis US. "With Kisqali, we have the opportunity to reduce the risk of recurrence for these patients with early breast cancer, while we continue to offer significant survival benefit to patients living with metastatic disease.” 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 TRIO5,6. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable5,6. The primary endpoint of NATALEE is invasive disease-free survival (iDFS) as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria5,6. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial5,6. 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 Commission7,8. 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 ET7. In the EU, Kisqali is approved in combination with an AI for the adjuvant treatment of patients with HR+/HER2- early breast cancer at high risk of recurrence; and 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 progression8. In pre- or peri-menopausal women, the ET should be combined with a luteinizing hormone-releasing hormone agonist7,8. 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 39. Kisqali approvals in EBC from regulatory authorities worldwide are ongoing, including recent approval from China’s National Medical Products Administration10. 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- MBC when combined with an AI9, 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 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. For more than 30 years, Novartis has been at the forefront of driving scientific advancements for people touched by breast cancer and improving clinical practice in collaboration with the global community. With one of the most comprehensive breast cancer portfolios and pipeline, Novartis leads the industry in the discovery of new therapies and combinations in HR+/HER2- breast cancer, the most common form of the disease. Beyond medicines, Novartis is leading efforts to encourage early detection and working to remove access barriers faced by patients along their care journey. Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide. References Kalinsky K et al. Efficacy and safety of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in NATALEE: Analysis across menopausal status and age. Presented at the American Society of Clinical Oncology Annual Meeting, June 1, 2025. Chicago, USA. American Cancer Society. Cancer Facts & Figures 2025. American Cancer Society. 2025. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2025/2025-cancer-facts-and-figures-acs.pdf. Accessed May 2025. Abdou Y et al. Real-world (RW) analysis of characteristics and risk of recurrence (ROR) in Black patients (pts) with HR+/HER2- early breast cancer (EBC) eligible for NATALEE. Presented at the American Society of Clinical Oncology Annual Meeting, June 2, 2025. Chicago, USA. Graff SL et al. Adjuvant WIDER: A phase 3b trial of ribociclib (RIB) + endocrine therapy (ET) as adjuvant treatment (tx) in a close-to-clinical-practice patient (pt) population with HR+/HER2− early breast cancer (EBC). Presented at the American Society of Clinical Oncology Annual Meeting. June 2, 2025. Chicago, USA. Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus Endocrine Therapy in Early Breast Cancer. N Engl J Med. 2024;390(12):1080-1091. doi:10.1056/NEJMoa2305488 Clinicaltrials.gov. NCT03701334. A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/ HER2- Early Breast Cancer (NATALEE). Available from: https://clinicaltrials.gov/study/NCT03701334. Accessed May 2025. Kisqali. Prescribing Information (US FDA). Novartis Pharmaceuticals Corporation; 2017. Accessed May 2025. https://www.novartis.com/us-en/sites/novartis_us/files/kisqali.pdf Kisqali. Summary of product characteristics (SmPC). Novartis Europharm Limited; 2017. Accessed May 2025. https://www.ema.europa.eu/en/documents/product-information/kisqali-epar-product-information_en.pdf NCCN Guidelines. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) - Breast Cancer. Accessed May 2025. https://www.nccn.org National Medical Products Administration. Drug Evaluation Information Disclosure: Drug Evaluation Approval Results. National Medical Products Administration. Published May 21, 2025. Accessed May 28, 2025. https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20250521151427103.html Yardley DA et al. Pooled exploratory analysis of survival in patients (pts) with HR+/HER2- advanced breast cancer (ABC) and visceral metastases (mets) treated with ribociclib (RIB) + endocrine therapy (ET) in the MONALEESA (ML) trials. Poster presented at the European Society of Medical Oncology Congress. September 9-13, 2022. Paris, France. Neven P et al. Updated overall survival (OS) results from the first-line (1L) population in the Phase III MONALEESA-3 trial of postmenopausal patients with HR+/HER2- advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL). Mini oral presented at the European Society for Medical Oncology Breast Cancer Congress. May 4, 2022. Paris, France. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022;386(10):942-950. doi:10.1056/NEJMoa2114663 Hortobagyi GN et al. Overall survival (OS) results from the phase III MONALEESA (ML)-2 trial of postmenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. LBA 17. Proffered paper presented at the European Society of Medical Oncology Congress, September 16-21, 2021. Lugano, Switzerland. Im SA, Lu YS, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381(4):307-316. doi:10.1056/NEJMoa1903765 Slamon DJ, Neven P, Chia S, et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2020;382(6):514-524. doi:10.1056/NEJMoa1911149 Slamon DJ et al. Overall survival (OS) results of the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). LBA7_PR. Presented at the European Society of Medical Oncology Congress, September 29, 2019. Barcelona, Spain. Slamon DJ et al. Updated overall survival (OS) results from the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2− advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). Presented at the American Society of Clinical Oncology Annual Meeting, June 5, 2021. Chicago, USA. Tripathy D et al. Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. Presented at the San Antonio Breast Cancer Symposium, December 9, 2020. Texas, USA. Yardley D et al. Overall survival (OS) in patients (pts) with advanced breast cancer (ABC) with visceral metastases (mets), including those with liver mets, treated with ribociclib (RIB) plus endocrine therapy (ET) in the MONALEESA (ML) -3 and -7 trials. Presented at the American Society of Clinical Oncology Annual Meeting, June 2020. Chicago, USA. O’Shaughnessy J et al. Overall survival subgroup analysis by metastatic site from the Phase III MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with HR+/HER2− advanced breast cancer. Presented at the San Antonio Breast Cancer Symposium, December 7-10, 2021. Texas, USA. European Society of Medical Oncology (ESMO). ESMO MCBS scorecards; NATALEE. Accessed May 2025. https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards/scorecard-468-1 European Society for Medical Oncology. Magnitude of Clinical Benefit Scale Scorecard. Accessed May 2025. https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards?scorecard=158-1 European Society for Medical Oncology. Magnitude of Clinical Benefit Scale Scorecard. Accessed May 2025. https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards?scorecard=9-1 The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultASCODrug Approval

02 Jun 2025

·www.fiercebiotech.com

ASCO: AstraZeneca\'s oral SERD tied to 56% PFS benefit in phase 3 breast cancer trial

AstraZeneca reaffirmed that data on the key secondary endpoints of overall survival or time to second disease progression had been immature at the time of the interim analysis\n AstraZeneca has produced some fresh data to back up its blockbuster ambitions for camizestrant, tying the oral SERD to a 56% improvement in progression-free survival (PFS) in a phase 3 breast cancer study.The Serena-6 study had a novel design that reflected an unmet need in individuals with HR-positive, HER2-negative advanced breast cancer. All 315 patients received an aromatase inhibitor and a CDK4/6 inhibitor—either Eli Lilly’s Verzenio, Novartis’ Kisqali or Pfizer’s Ibrance—as their first-line treatment.Physicians then monitored circulating tumor DNA to spot ESR1 mutations. If a mutation was found before disease progression, patients switched to camizestrant and stayed on the CDK4/6 drug.AstraZeneca revealed back in February that, based on an interim readout, the trial had hit its primary endpoint of PFS but saved the detailed data for the American Society of Clinical Oncology (ASCO) meeting in Chicago on Sunday. Specifically, patients who were moved up to camizestrant and a CDK4/6 inhibitor had a median PFS of 16 months, compared to 9.2 months for those who only received the first-line treatment of an aromatase inhibitor and a CDK4/6 inhibitor.As with the previous announcement in February, AstraZeneca reaffirmed that data on the key secondary endpoints of overall survival or time to second disease progression (PFS2) had been immature at the time of the interim analysis. All the drugmaker had to add yesterday was that “a trend toward extended treatment benefit” has so far been observed when it came to PFS2.The company instead wanted to focus on an exploratory endpoint of “time to deterioration in quality of life.” Here, AstraZeneca could point to a 47% reduction in deterioration of global health status and quality of life among the camizestrant cohort—with a median time of 23 months before these patients saw their health status deteriorate compared to 6.4 months for other patients.“As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumour DNA to detect emerging resistance and change therapy at the earliest opportunity; SERENA-6 is redefining the clinical paradigm in breast cancer,” Susan Galbraith, Ph.D., executive vice president of oncology R&D at AstraZeneca, said in a June 1 release. “Camizestrant is the first and only next-generation oral SERD and complete estrogen receptor antagonist to demonstrate benefit in combination with widely approved CDK4/6 inhibitors in this first-line setting, and these results support its potential as a new standard-of-care endocrine therapy backbone in the treatment of HR-positive breast cancer,” Galbraith added.When it came to safety, 60% of patients receiving camizestrant experienced adverse events of grade 3 or higher, compared to 40% of the comparator cohort. But AstraZeneca argued this was “consistent with the longer duration of exposure to the combination of camizestrant and CDK4/6 inhibitors in the trial.”The majority of these side effects were hematological events typically associated with CDK4/6 inhibitor treatment and included neutropenia and leukopenia—abnormally low concentration of a type of white blood cell—and anemia.The PFS endpoint is the first of a series of milestones for the program. AstraZeneca is running another trial in a broader first-line population and two adjuvant studies. Through the program, the company is aiming to establish camizestrant as a new backbone therapy and hit a peak sales target that AstraZeneca CEO Pascal Soriot has set at more than $5 billion.But AstraZeneca could face competition. Lilly reported phase 3 data on its oral SERD imlunestrant in patients who progressed on an aromatase inhibitor late last year. Roche is aiming to have data on giredestrant, its challenger for the market, sometime from mid-2025 onward. AstraZeneca sees the safety profile of its candidate and ability to combine it with a range of other drugs as differentiators.

$ASCO: AstraZeneca\'s oral SERD tied to 56% PFS benefit in phase 3 breast cancer trial$

Phase 3Clinical ResultASCO

02 Jun 2025

·www.globenewswire.com

Relay Therapeutics Announces Updated Data for RLY-2608 + Fulvestrant Further Demonstrating Clinically Meaningful Progression Free Survival at ASCO 2025

Updated interim data remain consistent, showing 10.3-month median PFS overall and 11.0-month median PFS in 2L patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer Data continue to support planned initiation of pivotal study in mid-2025 Next-generation triplet combinations with atirmociclib (CDK4-selective) & ribociclib ongoing CAMBRIDGE, Mass., June 02, 2025 (GLOBE NEWSWIRE) -- Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies, today announced updated interim clinical data for RLY-2608, the first known investigational allosteric, pan-mutant and isoform-selective inhibitor of PI3Kα. The updated data have a median duration of follow-up of 12.5 months and remain consistent with data shared in December 2024. They show a median progression free survival (PFS) of 11.0 months in second line (2L) patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer who received RLY-2608 600mg twice daily (BID) + fulvestrant. These data are being presented today at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting. “The treatment options for CDK4/6-experienced patients with PI3Kα mutations has not meaningfully advanced in the past 10 years and recent data disclosures and trial discontinuations highlight the level of unmet need in this population. We are encouraged by the consistency of these updated RLY-2608 + fulvestrant data, which continue to show the potential benefit of a mutant-selective PI3Kα inhibitor for improving both the tolerability profile and progression free survival compared to standard of care,” said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics. “We look forward to starting the first mutant-selective PI3Kα Phase 3 trial, ReDiscover-2, in the middle of this year.” ReDiscover – RLY-2608 First-in-Human Study RLY-2608 is currently being evaluated in ReDiscover, an ongoing first-in-human study, which was designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of RLY-2608 in combination with fulvestrant, and in combination with fulvestrant and ribociclib or atirmociclib (Pfizer’s selective CDK4 inhibitor). The RLY-2608 + fulvestrant arm of the study, as of the March 26, 2025 interim data cut-off for this arm, had enrolled 118 patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer across all doses in both the dose escalation and dose expansion portions of the study, including 64 patients at the company’s recommended Phase 3 dose (RP3D) of 600mg BID administered in the fasted state (fasted). Among these 64 patients, 31 had a kinase mutation and 33 had a non-kinase mutation. Twelve patients also had a PTEN or AKT co-mutation and were therefore excluded from the efficacy analysis, consistent with the planned pivotal population. All RLY-2608 + fulvestrant patients across doses had received a significant level of prior therapy in the advanced setting, including at least one prior endocrine therapy and at least one prior CDK4/6 inhibitor. Among the 64 patients who received the RP3D, 44% of patients (n=28) had received two or more prior lines of therapy. The RLY-2608 + atirmociclib + fulvestrant arm of the study, initiated in Q4 2024, continues to enroll patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer in dose escalation, as does the RLY-2608 + ribociclib + fulvestrant arm. Promising Efficacy Consistently Demonstrating mPFS Greater Than 10 Months Among the 52 RLY-2608 + fulvestrant patients who received the RP3D and did not have a PTEN or AKT co-mutation: Median follow-up was 12.5 monthsThe median PFS was 10.3 months for all patients and 11.0 months for 2L patients For 2L patients, median PFS was 18.4 months for patients with kinase mutations and 8.5 months for patients with non-kinase mutations Clinical benefit rate (CBR) was 67% across all patients (35 of 52 CBR-evaluable patients; CBR defined as the proportion of patients with complete response, partial response or stable disease for at least 24 weeks)Among the 31 patients with measurable disease, 12 achieved a partial response (PR) (39% confirmed objective response rate, ORR) 81% of patients experienced tumor reductions (25/31)Among the 15 patients with measurable disease who had a kinase mutation, two thirds achieved a PR (67% confirmed ORR; n=10)Among the 15 patients who had received prior fulvestrant, 6 achieved a PR (40% confirmed ORR) Maintained Meaningfully Differentiated Tolerability Profile RLY-2608 + fulvestrant was generally well tolerated in the 118 patients treated across all doses as of the data cut-off date. The overall tolerability profile consisted of mostly low-grade treatment-related adverse events (TRAEs) that were manageable and reversible. Safety outcomes were generally as expected across dose levels based on exposure and consistent with mutant-selective PI3Kα inhibition. Among the 64 patients who received the RP3D: The low rate of TRAE-related dose modifications allowed for 92% median dose intensityOnly two patients discontinued treatment due to TRAEs (Grade 1 pruritis; Grade 1 nausea, loss of appetite)The majority of hyperglycemia was Grade 1; only two patients (3%) experienced Grade 3 hyperglycemia; no Grade 4-5 hyperglycemiaOnly 36% of patients experienced a Grade 3 TRAE; no Grade 4-5 TRAEs Continued Progression of Front-Line Breast Cancer Regimens Two front-line triplet regimens are being progressed – one with Pfizer’s investigative selective-CDK4 inhibitor atirmociclib and one with the existing CDK4/6 standard-of-care ribociclib. Dose escalation is ongoing for both arms and both are currently at biologically active doses. Anticipated RLY-2608 Next Steps Breast Cancer: Initiate Phase 3 ReDiscover-2 (NCT06982521) study of RLY-2608 + fulvestrant in mid-2025Continue dose escalation for additional breast cancer combination arms Vascular Malformations: Continue enrollment of Ph1/2 ReInspire study in vascular malformations The data presentation from ASCO is available on the Relay Therapeutics website in the “Publications/Presentations” section through the following link: https://relaytx.com/publications/. About RLY-2608 RLY-2608 is the lead program in Relay Therapeutics’ efforts to discover and develop mutant selective inhibitors of PI3Kα, the most frequently mutated kinase in all cancers, with oncogenic mutations detected in about 14% of patients with solid tumors. RLY-2608 has the potential, if approved, to address more than 300,000 patients per year in the United States, one of the largest patient populations for a precision oncology medicine. Traditionally, the development of PI3Kα inhibitors has focused on the active, or orthosteric, site. The therapeutic index of orthosteric inhibitors is limited by the lack of clinically meaningful selectivity for mutant versus wild-type (WT) PI3Kα and off-isoform activity. Toxicity related to inhibition of WT PI3Kα and other PI3K isoforms results in sub-optimal inhibition of mutant PI3Kα with reductions in dose intensity and frequent discontinuation. The Dynamo® platform enabled the discovery of RLY-2608, the first known allosteric, pan-mutant, and isoform-selective PI3Kα inhibitor, designed to overcome these limitations. Relay Therapeutics solved the full-length cryo-EM structure of PI3Kα, performed computational long time-scale molecular dynamic simulations to elucidate conformational differences between WT and mutant PI3Kα, and leveraged these insights to support the design of RLY-2608. RLY-2608 is currently being evaluated in a first-in-human study designed to treat patients with advanced solid tumors with a PIK3CA (PI3Kα) mutation. For more information on RLY-2608, please visit here. About Relay Therapeutics Relay Therapeutics (Nasdaq: RLAY) is a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies with the goal of bringing life-changing therapies to patients. As the first of a new breed of biotech created at the intersection of complementary techniques and technologies, Relay Therapeutics aims to push the boundaries of what’s possible in drug discovery. Its Dynamo® platform integrates an array of leading-edge computational and experimental approaches designed to drug protein targets that have previously been intractable or inadequately addressed. Relay Therapeutics’ initial focus is on enhancing small molecule therapeutic discovery in targeted oncology and genetic disease indications. For more information, please visit www.relaytx.com or follow us on Twitter. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding Relay Therapeutics’ strategy, business plans and focus; the progress and timing of the clinical development of the programs across Relay Therapeutics’ portfolio; the expected therapeutic benefits and potential efficacy and tolerability of RLY-2608, both as a monotherapy and in combination with other agents, and its other programs, as well as the clinical data for RLY-2608; the interactions with regulatory authorities and any related approvals; the potential market opportunity for RLY-2608; the cash runway projection and the expectations regarding Relay Therapeutics’ use of capital and expenses. The words “may,” “might,” “will,” “could,” “would,” “should,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions, or the negative thereof, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of global economic uncertainty, geopolitical instability and conflicts, or public health epidemics or outbreaks of an infectious disease on countries or regions in which Relay Therapeutics has operations or does business, as well as on the timing and anticipated results of its clinical trials, strategy, future operations and profitability; the delay or pause of any current or planned clinical trials or the development of Relay Therapeutics’ drug candidates; the risk that the preliminary or interim results of its preclinical or clinical trials may not be predictive of future or final results in connection with future clinical trials of its product candidates and that interim and early clinical data may change as more patient data become available and are subject to audit and verification procedures; Relay Therapeutics’ ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of its planned interactions with regulatory authorities; and obtaining, maintaining and protecting its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Relay Therapeutics’ most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Relay Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Relay Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Contact:Pete Rahmerprahmer@relaytx.com Media:Dan Budwick1AB973-271-6085dan@1abmedia.com

Clinical ResultASCOPhase 3

100 Deals associated with Ribociclib Succinate

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KEGG	Wiki	ATC	Drug Bank
-	Ribociclib Succinate	L01XE	DB11730

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Advanced breast cancer	Canada	Novartis Pharmaceuticals Canada, Inc.	02 Mar 2018
Metastatic breast cancer	Canada	Novartis Pharmaceuticals Canada, Inc.	02 Mar 2018
Hormone receptor positive HER2 negative breast cancer	United States	Novartis Pharmaceuticals Corp.	13 Mar 2017

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced HER2-Positive Breast Carcinoma	Phase 3	United States	Novartis AG	28 Mar 2022
Advanced HER2-Positive Breast Carcinoma	Phase 3	Portugal	Novartis AG	28 Mar 2022
Advanced HER2-Positive Breast Carcinoma	Phase 3	Spain	Novartis AG	28 Mar 2022
Early Stage Breast Carcinoma	Phase 3	-	Novartis Pharmaceuticals Corp.	31 Mar 2018
HER2-negative breast cancer	Phase 3	Italy	Novartis Pharmaceuticals Corp.	02 Feb 2018
Leukodystrophy, Hypomyelinating, 6	Phase 3	Italy	Novartis Pharmaceuticals Corp.	02 Feb 2018
Locally advanced breast cancer	Phase 3	Italy	Novartis Pharmaceuticals Corp.	02 Feb 2018
Breast Cancer	Phase 3	United States	Novartis Pharmaceuticals Corp.	07 Jun 2017
Advanced cancer	Phase 3	United States	Novartis Pharmaceuticals Corp.	30 Nov 2016
Advanced cancer	Phase 3	Argentina	Novartis Pharmaceuticals Corp.	30 Nov 2016

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NATALEE (ASCO2025)	Not Applicable	Hormone receptor positive HER2 negative breast cancer Adjuvant	-	Ribociclib + Aromatase Inhibitor (AI)	xbyaenvbmh(huueiyamkj): HR = 0.715	Positive	30 May 2025
				Nonsteroidal Aromatase Inhibitor (NSAI)
NCT05563220 (ELEVATE, ASCO2025)	Phase 1/2	ER-positive/HER2-negative Breast Cancer	-	Elacestrant + Ribociclib	zwlylyhgti(zyvxutxocx) = 43% (7% ≥Gr3) with Ela + Eve rriijfzxhn (ujznyxajeu ) View more	-	30 May 2025
				Elacestrant + Everolimus
PALMARES-2 (ASCO2025)	Not Applicable	-	3,598	Palbociclib	ovtkbuqnxg(tcgsglvjca) = nmzafxchcd swesjcqdnw (hzyuohbjrj ) View more	Negative	30 May 2025
NCT03913234 (BR 18-2 MINI, ASCO2025)	Phase 1/2	Advanced breast cancer First line HR+ \| HER2+	77	Ribociclib 600 mg QD + Letrozole 2.5 mg QD + Trastuzumab 8 mg/kg loading then 6 mg/kg every 3 weeks	letftizkos(gcfycitiwa) = unpvjcuaot fqocgerdzf (hqpuojeizp, 19.6 - NA) View more	Positive	30 May 2025
BRIGHT-1 and BRIGHT-2 (ASCO2025)	Not Applicable	Hormone receptor positive HER2 negative breast cancer First line	697	Bireociclib containing regimens	flnubtbnlg(gmfszfnlqp) = dqbsntbktz bpwttxirsx (sljbpqbyoa ) View more	Positive	30 May 2025
				Bireociclib (Heavily pretreated MBC pts)	flnubtbnlg(gmfszfnlqp) = fnwhuljxau bpwttxirsx (sljbpqbyoa )
NCT03839823 (RIGHT Choice, ASCO2025)	Phase 2	Advanced breast cancer First line HR+ \| HER2-	222	Ribociclib + Letrozole/Anastrozole + Goserelin	vfwoqinnty(qdtgmkwhzk) = jckfnrrqnh jjrvfqjgyo (hwkavyenoj ) View more	Positive	30 May 2025
				Combination Chemotherapy	vfwoqinnty(qdtgmkwhzk) = xnokkoqswe jjrvfqjgyo (hwkavyenoj ) View more
NCT03701334 (NATALEE, ASCO2025)	Phase 3	Early Stage Breast Carcinoma \| Hormone receptor positive HER2 negative breast cancer Adjuvant Ki-67	-	Ribociclib + Nonsteroidal Aromatase Inhibitor	pfpwxszaba(stiyxdfsij) = Alanine aminotransferase elevation was the most common AE leading to discontinuation in the PreM (6.2%) and PostM groups (8.0%) xeuosqrjnn (bgzlswfgwx )	Positive	30 May 2025
				Nonsteroidal Aromatase Inhibitor alone
NCT04055493 (WSG ADAPTcycle, ESMO_BC2025)	Phase 3	Hormone receptor positive HER2 negative breast cancer Neoadjuvant OncotypeDx	-	Ribociclib + endocrine treatment	evyslszdiu(rjehdybjxe) = Most frequent ≥ grade 3 AE were neutropenia (Ribo/CT 34.3 vs. 13.3%) wzjhgaspvi (qblysetqnt ) View more	Positive	15 May 2025
				Standard chemotherapy + endocrine treatment
RibOB study (ESMO_BC2025)	Phase 4	Hormone receptor positive HER2 negative breast cancer First line G8 score \| Leukocyte telomere length (LTL) \| plasma inflammatory cytokines ... View more	70	Ribociclib 600 mg	yzopmhgioc(rowaephsxg) = qqrreinaqh toilbpejew (iwcmyrpphj, 24 - NE) View more	Positive	14 May 2025
RIBANNA (ESMO_BC2025)	Not Applicable	Advanced breast cancer First line	2,567	Ribociclib plus endocrine therapy	laghwnrtvz(jyarugxead) = fzwznfjrah uxugplkvqc (ueqgyedeoe, 71.0 - NR) View more	-	14 May 2025
				Endocrine monotherapy	laghwnrtvz(jyarugxead) = pxfhnyzzsn uxugplkvqc (ueqgyedeoe ) View more

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