On October 20, 2023 Exact Sciences Corp. (NASDAQ: EXAS), a leading provider of cancer screening and diagnostic tests, reported that it will present new data supporting the company’s research in early cancer detection, genomic testing, and treatment guidance at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, October 20-24, in Madrid, Spain (Press release, Exact Sciences, OCT 20, 2023, View Source [SID1234636191]).

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!

Exact Sciences will feature studies from across its multi-cancer early detection (MCED) and precision oncology portfolios, highlighting:

Two trials evaluating the company’s blood-based, MCED program1,2

OncoExTra data showing the frequency of the detection of actionable fusions, signals of some cancers, in nearly 8,000 people with solid tumors, helping inform treatment decisions by using next-generation sequencing (NGS) to assess a tumor’s RNA and DNA3
"At Exact Sciences, we are driving paradigm shifts in the early detection and treatment of cancer," said Jorge Garces, Ph.D., chief science officer, Exact Sciences. "With continued advances in understanding tumor biology and the precise identification of actionable biomarkers, our screening and diagnostic tools are improving the lives of people living with or at risk for cancer today – and are poised to transform the cancer landscape in the future."

Cancerguard

Exact Sciences is taking a robust and rigorous approach to developing an MCED test, and today unveiled its brand name, Cancerguard. Building upon decades of research, Exact Sciences is designing the Cancerguard test to harness the additive sensitivity of multiple biomarker classes to detect more early-stage cancers. The Cancerguard test will utilize a streamlined and standardized imaging-based diagnostic pathway, resulting in fewer follow-up procedures. The test is being developed to provide high specificity to help minimize false positives, while detecting multiple cancers, including those with the biggest impact on human health. To learn more, visit View Source

The company will host a symposium at the congress titled "Shifting the Paradigm of Cancer Detection: Multi Cancer Early Detection," featuring experts from leading oncology research institutions and Exact Sciences. The session will highlight research ushering in the era of MCED tests, including results from multiple studies that support a vision for the future where MCED testing, added to current recommended cancer screenings, may help identify more cancers in earlier stages and have an impact on public health.

Key Data Presentations at ESMO (Free ESMO Whitepaper) 20231-6

LBA24: Multiparametric prognostic score in early HR+/HER2- breast cancer:
Impact of Recurrence Score (RS), clinical-pathological factors, gene mutations and histology

Data embargoed until 00:05 CEST / 6:05 AM EDT on Thursday, 19 October 2023
Authors: Gluz, O. et al.
Date/Time: October 23, 2023, 11:05 AM CEST
Location: Bilbao Auditorium (Mini-Oral session, Breast Cancer Early Stage)

Key Takeaway: Exploratory analysis of data from Phase III ADAPT trial to determine if expanding use of clinical-pathological factors, including adaptive factors (e.g., Ki67 response), provides additional clinically useful prognostic information when added to the Recurrence Score in multivariable models.4

Abstract #183P: Frequency of actionable fusions in 7,735 patients with solid tumors

Data embargoed until 00:05 CEST / 6:05 PM EDT on Monday, October 16
Authors: McDonnell, K. et al.
Date/Time: October 21, 2023, 7:30 AM CEST
Location: Hall 8

Key Takeaway: Comprehensive genomic profiling approaches that include RNA sequencing can improve fusion detection compared to exome or targeted DNA sequencing alone. This study demonstrates the potential of the OncoExtra test to identify fusions that are relevant for determining therapy, disease prognosis or clinical trial eligibility.3

Abstract #317P: Awareness of genomic testing among patients with breast cancer in Europe

Data embargoed until 00:05 CEST / 6:05 PM EDT on Monday, October 16
Authors: Cardone, A. et al.
Date/Time: October 21, 2023, 7:30 AM CEST
Location: Hall 8

Key Takeaway: This study demonstrates that awareness of and access to genomic testing for breast cancer in Europe is sub-optimal. Genomic testing, involving expression profiling of tumor tissue removed from patients with breast cancer, is a powerful tool to help choose the most appropriate treatment for individual patients. Researchers surveyed women with HR+/ HER2 – breast cancer, eligible for genomic testing at the time of diagnosis, in five Western Europe countries about their awareness of genomic testing for treatment decision making.5

Abstract #189P: Design and enrollment for a classifier development study for a blood-based multi-cancer early detection (MCED) test

Data embargoed until 09:00 CEST / 3:00 PM EDT on Saturday, October 21
Authors: Douville, C. et al.
Date/Time: October 21, 2023, 09:00 AM CEST
Location: Hall 8

Key Takeaway: The Ascertaining Serial Cancer patients to Enable New Diagnostic 2 (ASCEND 2) study selected cancer types in an incidence-targeted manner, including rare and common cancers and evenly distributed stages. The ASCEND-2 study represents a racially, ethnically, and geographically diverse cohort for MCED test development.1

Abstract #202P: Participant perceptions and mammography adherence from DETECT-A, the first prospective interventional trial of a multi-cancer early detection (MCED) blood test

Data embargoed until 00:05 CEST / 6:05 PM EDT on Monday, October 16
Authors: Papadopoulos, N. et al.
Date/Time: October 21, 2023, from 09:00-17:00 CEST
Location: Hall 8

Key Takeaway: These data suggest that MCED testing did not significantly increase anxiety and depression or negatively impact mammography adherence for respondents with available data.2

Symposium at ESMO (Free ESMO Whitepaper) 2023:

Title: Shifting the Paradigm in Cancer Detection

Co-chairs:
Elizabeth O’Donnell, MD, Dana-Farber Institute & Harvard Medical School
Tomasz Beer, MD, FACP, Co-chair Chief Medical Officer and VP, Multi-cancer Early Detection, Exact Sciences
Faculty:
Nickolas Papadopoulos, PhD, Ludwig Center & The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Catherine Marinac, PhD, Dana Farber Institute & Harvard Medical School
Frank Diehl, PhD SVP Research and Development, Exact Sciences
Date/Time: Monday, October 23, 13:00 CEST
Location: Burgos Auditorium Hall 3, IFEMA MADRID, Madrid, Spain

Summary: Multi-cancer early detection (MCED) testing may help shift the paradigm in cancer screening, enabling detection of more cancers in earlier stages when they are more treatable. Results from multiple studies have demonstrated the potential value of MCED testing, and recent studies combining multiple biomarker classes in MCED test design have demonstrated the ability to enhance test performance for early-stage cancer detection. These results support a vision for the future where MCED testing is a part of routine primary care screening.6

This symposium is intended for healthcare providers and may discuss agents and products in development that have not been cleared or approved in your country or by any other national regulatory authority. The European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) does not endorse any company, or their products/services.

On October 20, 2023 SystImmune, Inc. (SystImmune), a clinical-stage biotechnology company, reported the presentation of pivotal data from its oncology portfolio at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (Press release, SystImmune, OCT 20, 2023, View Source [SID1234636190]). The event is scheduled to take place from October 20th to 24th in Madrid, Spain, where new clinical findings will be unveiled from trials involving BL-B01D1 and BL-M07D1.

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 expanded results from these clinical trials of BL-B01D1 will include data from patients with several solid tumor types in advanced stages and having multiple cycles of prior therapies. The data presented at ESMO (Free ESMO Whitepaper) builds on previously reported clinical data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), and recent recognition for BL-B01D1 conferred by industry experts at the 14th Annual World ADC meeting in San Diego who recognized SystImmune’s BL-B01D1 as a "Runner-Up" in the award category of "Most Promising Clinical Candidate".

"Encouraging signals of efficacy from the Ed-04 payload supported our decision to expand our pharmacopeia of targeting ADCs that deliver this novel and highly potent topoisomerase 1 inhibitor to a wider patient population with diverse diseases, while we expand our understanding of the exceptional properties of this linker-warhead combination," said Martin Olivo, M.D., CMO of SystImmune.

Presentations at the ESMO (Free ESMO Whitepaper) congress include:

Molecule Name

Title 

Abstract Number/
Presentation Details  

BL-B01D1

BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate,
in patients with non-small cell lung cancer: Updated results from first-
in-human phase I study

Abstract #1316MO

Oral Presentation: Saturday,
October 21st, 9:40 a.m. –
9:45 a.m. CEST

BL-M07D1

BL-M07D1, a HER2 antibody-drug conjugate in subjects with locally
advanced or metastatic HER2 expressing breast cancer and other solid
tumors.

Abstract #2017

Poster Available:
Monday, October 23rd

About BL-B01D1

The company is developing BL-B01D1, a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3. These proteins are highly expressed in most epithelial tumors. The tetravalent BL-B01D1 has two binding domains for distinct Growth Factor Receptors that drive cancer cell proliferation and survival. Inheriting the SI-B001 mechanisms of action, BL-B01D1 blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals. Upon antibody mediated internalization, BL-B01D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induced genotoxic stress activating pathways leading to cancer cell death.

About BL-M07D1

The company is developing BL-M07D1, a HER2 specific IgG-based ADC carrying DAR8 of the Ed-04 payload technology. The Ed-04 payload technology is composed of a potent topoisomerase 1 inhibitor and a serum-stable linker that is cleavable by cathepsin-B. By targeting proliferating cancer cells that express HER2, the BL-M07D1 has the potential to treat multiple epithelial cancer types, including breast and colorectal cancer types.

On October 20, 2023 Astrazeneca reported Positive results from a planned interim analysis of the MATTERHORN Phase III trial showed treatment with Imfinzi (durvalumab) in combination with standard-of-care FLOT neoadjuvant chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel given before surgery) demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of pathologic complete response (pCR) versus neoadjuvant chemotherapy alone for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers (Press release, AstraZeneca, OCT 20, 2023, View Source [SID1234636186]).

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!

These results will be presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 in Madrid, Spain (abstract #LBA73).

Treatment with Imfinzi plus neoadjuvant FLOT chemotherapy resulted in a pCR rate of 19% versus 7% for patients treated with neoadjuvant chemotherapy alone as assessed by blinded independent central review (BICR) (difference in pCR rate 12%; odds ratio [OR] 3.08; p<0.00001). The rate of either complete or near-complete responses was 27% with the Imfinzi combination and 14% with neoadjuvant chemotherapy alone.

The trial, which is assessing Imfinzi in combination with FLOT chemotherapy as a perioperative treatment (before and after surgery), will continue as planned to assess the primary endpoint of event-free survival (EFS) and the key secondary endpoint of overall survival (OS) to which the trial team, investigators and participants remain blinded.

Yelena Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York and principal investigator in the trial said: "Disease recurrence after curative-intent surgery is far too common for patients with resectable gastric and gastroesophageal junction cancers. These early MATTERHORN results showing encouraging pathologic complete responses give hope that adding durvalumab to FLOT chemotherapy in the future will offer a much-needed new treatment approach in the perioperative setting."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The results from MATTERHORN highlight the potential of early treatment for patients with gastric and gastroesophageal junction cancers using an immunotherapy and chemotherapy combination. These findings reinforce our commitment to improving outcomes in gastrointestinal cancers, where unmet need is high and treatment options are limited."

Imfinzi was generally well tolerated, and no new safety signals were observed in the neoadjuvant setting. Further, the safety and tolerability of adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination. Grade 3 or higher adverse events from all causes were similar between the two arms, occurring in 69% of patients treated with the Imfinzi-based regimen versus 68% for neoadjuvant chemotherapy alone.

Summary of results: MATTERHORN

BICR

Investigator-assessed

Imfinzi plus chemo
(n=474)

Chemo alone
(n=474)

Imfinzi plus chemo
(n=474)

Chemo alone
(n=474)

pCRa

Patients who achieved pCR %

19

7

22

8

Odds ratio (95% confidence interval [CI])

3.08 (2.03-4.67)

3.03 (2.05-4.48)

p-value

<0.00001

N/A

Combined complete and near-complete responsea

Patients who achieved a complete or near-complete response %

27

14

N/A

N/A

Odds ratio (95% CI)

2.19 (1.58-3.04)

N/A

a. BICR review was scored using Modified Ryan criteria

For patients treated with the Imfinzi-based regimen, 87% completed surgery compared to 84% of patients treated with neoadjuvant chemotherapy alone. In patients who had surgery, including patients with surgery attempted but not completed, the rate of R0 resection (patients having no macroscopic or microscopic residual tumour following surgery) was 86% across both arms. The rate of T0 resection (patients with no evidence of their primary tumour) was 23% for the Imfinzi-based regimen compared to 11% for neoadjuvant chemotherapy alone. The rate of N0 resection (patients with no lymph nodes containing cancer cells) was 52% for the Imfinzi-based regimen compared to 36%.

Notes

Gastric and GEJ cancers
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fourth highest leading cause of cancer mortality.2 Approximately one million new patients were diagnosed with gastric cancer in 2020, with 768,000 deaths reported globally.2

GEJ cancer is a type of gastric cancer that arises from and spans the area where the oesophagus connects to the stomach.3

By 2030, approximately 70,000 patients in the US, EU and Japan will be newly diagnosed with Stage II-III gastric or GEJ cancers.4 Disease recurrence is common in patients with resectable gastric cancer.1 Approximately one in four patients with gastric cancer who undergo surgery with curative intent develop recurrent disease within one year, reflecting a high unmet medical need.1 Additionally, the five-year survival rate remains poor, with only up to a third of patients alive at five years.5,6

MATTERHORN
MATTERHORN is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage II-IVA gastric and GEJ cancers. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, patients were randomised to receive 1500mg fixed dose of Imfinzi plus FLOT chemotherapy or placebo plus FLOT chemotherapy every four weeks for two cycles prior to surgery, followed by Imfinzi or placebo every four weeks for up to 12 cycles after surgery (including two cycles of Imfinzi or placebo plus FLOT chemotherapy and 10 additional cycles of Imfinzi or placebo monotherapy).

In the MATTERHORN trial, the primary endpoint is EFS, defined as the time from randomisation until progression that precludes surgery or requires non-protocol therapy, local or distant recurrence or progression of disease, or death due to any cause as assessed by BIRC according to RECIST 1.1 and/or local pathology testing. Key secondary endpoints include pCR rate, defined as the proportion of patients who have no detectable cancer cells in resected tumour tissue following neoadjuvant therapy, and OS. The trial randomised 948 participants at sites in the US, Canada, Europe, South America and Asia.

Imfinzi 
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer (BTC) and in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma (HCC) in the US, EU, Japan and several other countries based on the TOPAZ-1 and HIMALAYA Phase III trials, respectively.

In addition to its indications in gastrointestinal (GI) cancers, Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small-cell lung cancer (SCLC) based on the CASPIAN Phase III trial. Additionally, Imfinzi is approved in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial. Imfinzi is approved in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 200,000 patients have been treated with Imfinzi.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several GI cancers and other solid tumours. In GI cancers specifically, AstraZeneca has several ongoing registrational trials investigating Imfinzi across multiple liver cancer settings (EMERALD-1, EMERALD-2 and EMERALD-3) and in locally advanced oesophageal cancer (KUNLUN).

On October 20, 2023 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for rare and ultrarare diseases, reported the grant of 18,865 restricted stock units of the company’s common stock to 10 newly hired non-executive officers of the company (Press release, Ultragenyx Pharmaceutical, OCT 20, 2023, View Source [SID1234636185]). The awards were approved by the compensation committee of the company’s board of directors and granted under the Ultragenyx Employment Inducement Plan, with a grant date of October 16, 2023, as an inducement material to the new employees entering into employment with Ultragenyx in accordance with Nasdaq Listing Rule 5635(c)(4).

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 restricted stock units vest over four years, with 25% of the underlying shares vesting on each anniversary of the grant date, subject to the employee being continuously employed by the company as of such vesting dates.

On October 20, 2023 Novartis reported that it will present late-breaking results from a prespecified exploratory subgroup analysis of invasive disease-free survival (iDFS) from the pivotal Phase III NATALEE trial at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023. After 27.7 months of follow-up, the iDFS benefit with Kisqali (ribociclib) plus endocrine therapy (ET) was consistent across key prespecified subgroups, 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) (see table below) (Press release, Novartis, OCT 20, 2023, View Source [SID1234636184]). Results were also consistent with those in the overall trial population, reinforcing that the benefit was not driven by a specific patient subgroup1,2.

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!

iDFS results across key prespecified subgroups1:

Subgroup Treatment Arm, n 3-year iDFS rate, % HR (95% CI)
AJCC Stage II ribociclib + ET, 1011
ET alone, 1034 94
91 0.76
(0.53-1.10)
AJCC Stage III ribociclib + ET, 1528
ET alone, 1512 87
84 0.74
(0.59-0.93)
N0 ribociclib + ET, 285
ET alone, 328 94
89 0.63
(0.34-1.17)
N1-N3 ribociclib + ET, 2261
ET alone, 2219 90
87 0.77
(0.63-0.94)
Premenopausal
women & men ribociclib + ET, 1126
ET alone, 1132 91
89 0.72
(0.53-0.98)
Postmenopausal women ribociclib + ET, 1423
ET alone, 1420 90
86 0.78
(0.61-1.00)
<65 years old ribociclib + ET, 2142
ET alone, 2186 90
87 0.77
(0.62-0.94)
≥65 years old ribociclib + ET, 407
ET alone, 366 90
86 0.72
(0.46-1.14)
Ki-67 ≤20% ribociclib + ET, 1199
ET alone, 1236 92
90 0.80
(0.59-1.08)
Ki-67 >20% ribociclib + ET, 920
ET alone, 938 89
84 0.75
(0.56-1.00)
"Subgroup analyses provide a more comprehensive picture of clinical benefit for patients and are critical to guiding treatment decisions, as they help indicate how different breast cancer subgroups might respond to treatment," said Aditya Bardia, M.D., Attending Physician, Medical Oncology, Mass General Cancer Center and Associate Professor, Medicine, Harvard Medical School and NATALEE trial investigator. "Given the outcomes of patients treated with endocrine therapy alone, this analysis outlines the potential benefit of adding ribociclib to endocrine therapy to reduce the risk of recurrence. These data provide important insight into how we think about residual risk in this population and make adjuvant treatment decisions for patients with localized breast cancer."

"Despite endocrine therapy, cancer recurrence remains unpredictable, and too many patients diagnosed with stage II or III HR+/HER2- early breast cancer experience their cancer coming back. This analysis further reinforces the potential of ribociclib to address the need for a new adjuvant option that reduces the ongoing risk of recurrence consistently across many types of at-risk patients," said Jeff Legos, Executive Vice President, Global Head of Oncology Development at Novartis. "These results from the NATALEE trial add to the wealth of efficacy, safety and quality of life data suggesting that ribociclib, if approved, could provide healthcare providers with a new option to help keep their patients living well and cancer-free."

Further analysis of the NATALEE trial is ongoing. Additional data, including the final efficacy analysis of the NATALEE trial, will be shared at upcoming medical meetings.

About NATALEE
NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of ribociclib with ET as adjuvant treatment versus ET alone in patients with stage II and III HR+/HER2- EBC, being conducted in collaboration with TRIO2. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable2. The primary endpoint of NATALEE is iDFS as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria2. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial2.

Results previously announced at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2023 showed ribociclib plus ET, compared to ET alone, lowered the risk of cancer recurrence by 25.2% (HR=0.748; 95% CI: 0.618, 0.906; p=0.0014), along with consistent clinically meaningful iDFS benefit across key pre-specified subgroups: AJCC Tumor Stage II (HR=0.761; 95% CI: 0.525, 1.103), AJCC Tumor Stage III (HR=0.740; 95% CI: 0.592, 0.925), node-negative disease (HR=0.630; 95% CI: 0.341, 1.165), node-positive disease (HR=0.771; 95% CI: 0.630, 0.944), pre-menopausal women and men (HR=0.722; 95% CI: 0.530, 0.983), post-menopausal women (HR=0.781; 95% CI: 0.613, 0.997)2. Ribociclib data across all secondary efficacy endpoints was also consistent, including distant disease-free survival (DDFS) (26% risk reduction) and recurrence-free survival (RFS) (28% risk reduction), with a trend for improvement in overall survival (OS) (HR=0.759; 95% CI: 0.539, 1.068).

For these previously announced results, median study duration of follow-up was 34 months (range 21-48 months) with clinical benefits observed after approximately two years2. NATALEE explored a lower starting dose (400 mg) of ribociclib than the dose approved for treatment in metastatic breast cancer (MBC) (600 mg) with the goal to minimize disruptions to patient quality of life without compromising efficacy. The safety profile of ribociclib at 400 mg was observed to have lower rates of symptomatic adverse events (AEs) and less need for dose modifications when administered up to three years2. The most frequently reported AEs of special interest (grade 3 or higher) were neutropenia (43.8%) and liver-related AEs (e.g. elevated transaminases) (8.3%).

*Results based on pre-specified interim analysis for OS at time of primary iDFS analysis; additional follow-up is planned to obtain more mature OS data.