GlobeNewswire

Novartis investigational checkpoint inhibitor tislelizumab met primary endpoint of overall survival in pivotal Phase III trial of esophageal cancer after systemic therapy

Share
  • Tislelizumab demonstrated a 30% reduction in the risk of death and extended median overall survival by 2.3 months compared to chemotherapy in advanced or metastatic esophageal squamous cell carcinoma after prior systemic therapy1
  • Additional Phase II data presented at ASCO showed tislelizumab demonstrated durable anti-tumor activity in patients with microsatellite instability-high, or mismatch-repair-deficient, solid tumors2

Basel, June 4, 2021 — Novartis announced today results from the pivotal Phase III RATIONALE 302 trial showing the investigational anti-PD-1 immune checkpoint inhibitor tislelizumab improved overall survival (OS) versus chemotherapy (median 8.6 months vs. 6.3 months, p=0.0001).1 The study evaluated tislelizumab in patients with unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who had received prior systemic therapy. Results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Results from RATIONALE 302 in ESCC showed tislelizumab extended median OS by 2.3 months compared to chemotherapy with a 30% reduction in the risk of death (HR=0.70, 95% CI: 0.57-0.85, p=0.0001).1 In PD-L1 positive patients, tislelizumab extended median OS by 3.5 months with a 46% reduction in the risk of death (HR=0.54, 95% CI: 0.36-0.79, p=0.0006).1

“These data show that tislelizumab has the potential to help patients with esophageal squamous cell carcinoma – one of the deadliest types of cancers – live longer,” said Jeff Legos, Ph.D., MBA, Senior Vice President and Head of Oncology Drug Development. “We are excited about these results from the newest asset in our portfolio of transformational medicines and look forward to sharing these data with regulatory authorities, as we continue to explore the full potential of this uniquely designed anti-PD-1 antibody.”

Treatment with tislelizumab demonstrated median progression-free survival (PFS) of 1.6 months compared to 2.1 months (HR=0.83, 95% CI: 0.67–1.01). Tislelizumab demonstrated a higher and more durable anti-tumor activity than chemotherapy (objective response rate [ORR], 20.3% vs. 9.8%; median duration of response [DoR], 7.1 months vs. 4.0 months).1

The discontinuation rate due to treatment-related adverse events (TRAEs) was lower in patients who received tislelizumab (6.7%) compared to chemotherapy (13.8%). The most common all-grade TRAEs (≥10%) with tislelizumab were increased aspartate aminotransferase (11.4%), anemia (11%) and hypothyroidism (10.2%). No new safety signals were identified.1

"Most patients with this type of esophageal cancer are diagnosed with advanced disease, resulting in a poor prognosis for this difficult-to-treat cancer," said Jaffer Ajani, M.D., professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. "The impact tislelizumab had on survival compared to chemotherapy in this study is highly meaningful and encouraging news for patients, caregivers and treating oncologists.”

Esophageal squamous cell carcinoma is the most common type of esophageal cancer globally and the sixth leading cause of cancer-related death worldwide.3 Each year, esophageal cancer claims nearly as many lives as colon cancer across the globe.3 More than two-thirds of patients with ESCC have advanced or metastatic disease at the time of diagnosis.4 The average five-year survival rate is only five percent.5

RATIONALE 302 is a randomized, global Phase III study assessing tislelizumab versus chemotherapy in patients with advanced unresectable/metastatic ESCC after prior systemic therapy. The primary endpoint is OS in the intent-to-treat (ITT) population. The key secondary endpoint is OS in PD-L1 positive patients (vCPS ≥10%). Additional secondary endpoints included PFS, ORR, DoR and safety endpoints.1

Data on tislelizumab in MSI-H cancers presented
The RATIONALE 209 study reported that tislelizumab showed durable anti-tumor activity in patients with previously treated, locally advanced, unresectable or metastatic microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) cancers, which are known to be more responsive to immune checkpoint modulation. Treatment with tislelizumab demonstrated an ORR of 45.9% among all tumor types, including four complete responses (CR) and 30 partial responses (PR). No disease progression was reported in the 34 responders (CR + PR), with a 12-month DoR rate of 100%).2

Five percent of patients treated with tislelizumab discontinued treatment due to TRAEs, and no new safety signals were identified. Grade ≥3 TRAEs occurred in 42.5% of patients.2

MSI-H cancer cells have a defect in the ability to correct mistakes that occur when DNA is copied, leading to mutations that contribute to cancerous growth. Many types of cancer may have a high level of microsatellite instability, but it is seen most often in CRC, gastric cancer and endometrial cancer.6

RATIONALE 209 is a single-arm, open-label Phase II study evaluating the efficacy and safety of tislelizumab monotherapy in adult patients with previously treated, locally advanced, unresectable or metastatic histologically confirmed MSI-H/dMMR solid tumors. Radiological imaging was performed at nine weeks, then every six weeks for the first year of therapy and every 12 weeks thereafter. The primary endpoint was IRC-assessed ORR. Secondary endpoints included time to response, DoR, disease control rate, PFS, OS and safety.2

Visit https://www.hcp.novartis.com/virtual-congress/a-2021/ for the latest information from Novartis, including our commitment to the Oncology community, and access to our ASCO21 Virtual Scientific Program data presentations (for registered participants).

About tislelizumab
Tislelizumab was specifically engineered to minimize binding to macrophage Fcγ receptors, a potential mechanism of anti–PD-1 resistance.7 Tislelizumab is an important component of Novartis’s immuno-oncology strategy – one of four bold approaches to reimagining cancer and transforming patients’ lives.

In an agreement finalized earlier this year, BeiGene granted Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan through a collaboration and license agreement.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 110,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.

Novartis is on Twitter. Sign up to follow @Novartis at https://twitter.com/novartisnews
For Novartis multimedia content, please visit https://www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com

References

  1. Shen L, Kato K, Kim S-B, et al. RATIONALE 302: Randomized, Phase 3 study of tislelizumab vs chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma. ePoster presentation at American Society of Clinical Oncology Annual Meeting (ASCO); June 2021
  2. Li J, Xu Y, Zang A, et al. A Phase 2 study of tislelizumab monotherapy in patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high/mismatch repair deficient solid tumors. ePoster presentation at American Society of Clinical Oncology Annual Meeting (ASCO); June 2021
  3. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2018;68(6):394-424.
  4. Chen Z, Ren Y, Du XL, et al. Incidence and survival differences in esophageal cancer among ethnic groups in the United States. Oncotarget. 2017;8(29):47037-47051.
  5. Howlader N, et al. SEER Cancer Statistics Review, 1975–2017. National Cancer Institute, MD, USA (2020). https://seer.cancer.gov /csr/1975_2017/
  6. National Cancer Institute. Microsite instability-high cancer. Accessed May 5, 2021. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/microsatellite-instability-high-cancer
  7. Zhang T, Song X, Xu L, et al. The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions. Cancer Immunol Immunother. 2018;67(7):1079-1090.

# # #

Novartis Media Relations
E-mail: media.relations@novartis.com

Anja von Treskow
Novartis External Communications
+41 61 324 2279 (direct)
+41 79 392 8697 (mobile)
anja.von_treskow@novartis.com



Julie Masow
Novartis US External Communications
+1 862 579 8456
Julie.masow@novartis.com
Mary Curtin Creaser
Novartis Oncology
+1 862 345 4102 (mobile)
mary.curtin_creaser@novartis.com

Novartis Investor Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations@novartis.com

Central North America
Samir Shah +41 61 324 7944 Sloan Simpson +1 862 778 5052
Thomas Hungerbuehler        
Isabella Zinck
+41 61 324 8425
+41 61 324 7188
To view this piece of content from www.globenewswire.com, please give your consent at the top of this page.
To view this piece of content from ml-eu.globenewswire.com, please give your consent at the top of this page.

About GlobeNewswire

GlobeNewswire
GlobeNewswire
One Liberty Plaza - 165 Broadway
NY 10006 New York

https://globenewswire.com

GlobeNewswire is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.

Subscribe to releases from GlobeNewswire

Subscribe to all the latest releases from GlobeNewswire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from GlobeNewswire

Data analysis from dLab to boost the digitalization for Karlskoga Energi & Miljö24.6.2021 09:55:00 CEST | Press release

Regional utilities company Karlskoga Energi & Miljö AB has been using the smart data analytics solution from cleantech company Dlaboratory Sweden AB (publ) since 2020. A useful solution for avoiding power outages and identifying faults, dLab’s system is the starting point for the energy company’s digitalization journey. Energy company Karlskoga Energi & Miljö with its subsidiary Karlskoga Elnät has around 15 000 customers along a 1 700 km grid in the middle of the beautiful region of Värmland. Digitalization is a high priority throughout the organization, whether it means providing fiber optics for consumers, or the dInsight Analytics Platform from dLab. -The solution from dLab pushes us to work in a completely new way; from monitoring and analysis to becoming proactive, using data to prevent, rather than fix a problem. This requires new knowledge in the organization, but also a new way of working, says Jimmy Lundberg, Head of Distribution at Karlskoga Elnät. The company chose dLab’s s

Nokia launches next-generation AirScale 5G portfolio powered by ReefShark technology24.6.2021 09:00:00 CEST | Press release

Press Release Nokia launches next-generation AirScale 5G portfolio powered by ReefShark technology Nokia’s new, industry-leading 5G portfolio covers baseband, radio, and massive MIMO antennas offering huge 5G capacity, coverage, and easy deploymentIntroduces industry’s lightest massive MIMO units at 17kg enabling simplified deployments and faster time to marketNokia’s new comprehensive range of products are powered by Nokia’s latest generation of ReefShark chipsets Nokia’s extended Single RAN accelerates 5G rollouts and cuts overall RAN Total Cost of Ownership 24 June 2021 Espoo, Finland – Nokia today announced the global launch of its latest range of industry-leading AirScale 5G products covering baseband, remote radio heads, and massive MIMO active antennas with digital beamforming. The innovative solutions are powered by the latest generation of Nokia’s ReefShark System-on-Chip (SoC) chipsets and deliver the highest capacity and network performance while enabling efficient deploymen

Huvepharma Announces the Indicative Price Range, Publication of the Prospectus and Start of the Offer Period of Planned IPO24.6.2021 08:15:39 CEST | Press release

NOT FOR RELEASE, PUBLICATION OR DISTRIBUTION IN WHOLE OR IN PART, DIRECTLY OR INDIRECTLY, IN OR INTO THE UNITED STATES, CANADA, AUSTRALIA OR JAPAN OR ANY OTHER JURISDICTION IN VIOLATION OF THE RELEVANT LAWS OF SUCH JURISDICTION. This announcement is an advertisement for the purposes of the Prospectus Regulation EU 2017/1129 and underlying legislation, relating to the launch of the Offer (as defined below) by the Company and the proposed Admission (as defined below). This announcement does not constitute a prospectus. This announcement is for information purposes only and is not intended to constitute, and should not be construed as, an offer to sell or a solicitation of any offer to buy Shares (as defined below) in any jurisdiction, including the United States, Canada, Australia or Japan. Further details about the Offer and the Admission is included in the Prospectus (as defined below). The Prospectus has today been approved by the Netherlands Authority for the Financial Markets (Stich

FDA accepts application for Roche’s Port Delivery System with ranibizumab (PDS) for treatment of neovascular or “wet” age-related macular degeneration (nAMD)24.6.2021 07:00:00 CEST | Press release

If approved, PDS would be the first and only eye implant with continuous drug delivery that offers people living with nAMD an alternative to frequent eye injectionsA pivotal study showed PDS extends time between treatments up to six months for more than 98% of patients and provides vision outcomes equivalent to monthly ranibizumab injectionsThe European Medicines Agency has also validated the PDS Marketing Authorisation Application in nAMD Basel, 24 June 2021 - Roche (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA), under Priority Review, for Port Delivery System with ranibizumab (PDS) for the treatment of neovascular or “wet” age-related macular degeneration (nAMD). Neovascular AMD is a leading cause of blindness for people aged 60 and over and impacts approximately 20 million people worldwide.1,2,3 If approved, PDS would be a first-of-its-kind therapeutic approach, offering pe

ObsEva To Present Data on Two Clinical Development Programs at ESHRE Virtual 37th Annual Meeting24.6.2021 07:00:00 CEST | Press release

- Data from Phase 3 study ofYselty® (linzagolix) for the treatment of uterine fibroids to be discussed in an oral presentation; Top-line data from pilot study of Yselty for the treatment of severe adenomyosis to be presented in an ePoster- -Data from IMPLANT1 Phase 2 study of nolasiban for uterine contractility of IVF patients prior to embryo transfer to be presented in an ePoster - GENEVA, Switzerland and BOSTON– June 24, 2021 – ObsEva SA (NASDAQ: OBSV) (SIX: OBSN), a biopharmaceutical company developing and commercializing novel therapies to improve women’s reproductive health, today announced the presentation of data from two of its clinical development programs at the European Society of Human Reproduction and Embryology (ESHRE) Virtual 37th Annual Meeting, being held June 26 - July 1, 2021. Details of the presentations for the Yseltyprogram are as follows: Title: Long-Term Secondary Efficacy of Linzagolix for Heavy Menstrual Bleeding (HMB) Due to Uterine Fibroids (UF): 52-Week Res

Hyloris Successfully Renegotiates License Agreements for Lead Products with the Alter Pharma Group24.6.2021 07:00:00 CEST | Press release

Acquires all royalty rights to Maxigesic® IV Assumes sole responsibility for HY-075 and HY-038 – future profit split lapses Gains higher net profit margin for Fusidic Acid Cream in Canada Hyloris CEO and CBDO to resign from the Board of Directors of Alter Pharma Liège, Belgium – 24June 2021 – Hyloris Pharmaceuticals SA (Euronext Brussels: HYL), a specialty biopharma company committed to bringing innovative treatments that offer added value to underserved patient populations, today announces that it has successfully renegotiated and unwound its earlier license agreements with the Alter Pharma Group. Hyloris will pay the Alter Pharma Group a total lump sum of €5.25 million plus €0.5 million potential earn-out, thereby waiving any further future financial obligations towards the Alter Pharma Group. Hyloris Pharmaceuticals and the Alter Pharma Group have amended and unwound the earlier license agreements as follows: The patent and knowhow license agreement in relation to Maxigesic IV has b

Enento Group makes a strategic investment to add a unique Sales Intelligence service offering by acquiring a part of Goava Sales Intelligence AB with possibility to take majority24.6.2021 07:00:00 CEST | Press release

ENENTO GROUP PLC, STOCK EXCHANGE RELEASE ON 24 JUNE 2021 AT 8.00 A.M. EEST Enento Groupmakes a strategic investment to add a uniqueSales Intelligence service offering byacquiring apart of Goava Sales Intelligence AB with possibility to take majority Enento Group Plc has signed an agreement to acquire part of and become the largest shareholder of the Swedish sales intelligence services company Goava Sales Intelligence AB by subscribing to new preference shares in the company. Within the agreement, Enento in the first stage on 24 June 2021 acquires a 38,3 % (35,1 % fully diluted) shareholding in the company, and at the same time agrees to complete subsequent preference share subscriptions provided that the company fulfills certain preconditions laid out in the business plan, as well as acquires a purchase option to acquire all outstanding shares in the company after a mutually agreed business plan period ending in year 2024 and aiming at gaining a significant market position for the serv