HER2 negative Gastric Cancer

An Astellas Pharma drug designed to address a novel target has landed a highly anticipated FDA approval for a rare type of gastrointestinal cancer, making it the first therapy in a new class of oncology drugs. The regulatory decision announced Friday covers the first-line treatment of adults with advanced cases of gastric or gastroesophageal junction (GEJ) adenocarcinoma. These cancers must express the cancer protein claudin 18.2 (CLDN18.2), the target of the Astellas antibody, zolbetuximab. The Japanese pharmaceutical company will market the new drug under the brand name Vyloy. GEJ adenocarcinoma is a type of cancer in the area where the esophagus joins the stomach. According to Astellas, an estimated 130,263 in the U.S. people are living with gastric or GEJ cancer, which places it among the rarer cancers. CLDN18.2 is found only in stomach cells, not other healthy tissues. In gastrointestinal cancers, this protein is overexpressed, making it a valuable target for cancer drugs. Vyloy binds to CLDN18.2, activating two immune system pathways that kill cells expressing the target protein. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum FDA approval of Vyloy covers the treatment of gastric or GEJ cancers that are negative for a different cancer protein called HER2. That’s important because cancers positive for HER2 already have treatment options, such as Roche’s HER2-binding antibody, Herceptin, and the AstraZeneca and Daiichi Sankyo antibody drug conjugate Enhertu. Vyloy’s approval gives HER2-negative gastric and GEJ cancers patients a targeted treatment option for use in combination with standard of care chemotherapies. Astellas’s submission for Vyloy was based on results from two Phase 3 clinical trials that enrolled participants with advanced HER2-negative gastric or GEJ cancer that was positive for CLDN18.2. One study evaluated Vyloy in combination with the chemotherapy regimen known as FOLFOX6, comparing it to a placebo and FOLFOX6; the other trial tested the study drug and the chemo regimen known as CAPOX against a placebo and CAPOX. In both studies, the combination of Vyloy and chemo led to statistically significant improvement on the main goal of progression-free survival. The studies also achieved statistically significant improvement on the key secondary goal of overall survival. The most common side effects reported in these studies included nausea, vomiting, and decreased appetite. In Astellas’s announcement of Vyloy’s approval, Dr. Samuel Klempner, associate professor at Harvard Medical School and a medical oncologist at Massachusetts General Hospital, said that despite advances in first-line treatment of advanced gastric and GEJ cancers, there is still an unmet medical need for these patients. “The approval of Vyloy, based on the pivotal Phase 3 SPOTLIGHT and GLOW trials, brings forward a novel biomarker and new therapy for patients whose tumors are CLDN18.2 positive, and for those on the frontlines of treatment decision-making,” he said. presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB Vyloy was initially expected to receive an FDA decision early this year, but the agency rejected the drug’s application in January due to issues with the drug’s third-party manufacturer. The approval came ahead of the new Nov. 9 target date for a decision. Concurrent with the Vyloy approval, the FDA also approved a Roche companion diagnostic to identify patients eligible for treatment with the drug. Astellas gained Vyloy from its 2016 acquisition of privately held Ganymede Pharmaceuticals for €422 million (about $462 million) up front. Another €860 million (about $930 million) is tied to the achievement of milestones. With the FDA approval of Vyloy, the U.S. is now the fifth market for the new Astellas drug. Japan was the first country to approve the drug in a regulatory decision handed out in March. Since then, Vyloy has landed affirmative regulatory decision in the United Kingdom, South Korea, and the European Union. The drug is still under review in other markets around the world. There are other companies pursuing CLDN18.2. The contender of Boston-based Elevation Oncology is EO-3021, an antibody drug conjugate (ADC) currently in early-stage clinical development as a monotherapy for advanced solid tumors, including gastric, GEJ, pancreatic, and esophageal cancers. Data from this study are expected in the first half of 2025. A separate ongoing Phase 1 test is evaluating the Elevation drug in combination with Eli Lilly’s Cyramza and GSK’s Jemperli. Meanwhile, Merck KGaA could get a CLDN18.2 drug via a 2023 deal that granted it an option to license an ADC in development by Jiangsu Hengrui Pharmaceuticals.

The new VENTANA CLDN18 (43-14A) RxDx Assay helps fulfil an unmet medical need by enabling clinicians to identify patients with gastric or gastroesophageal junction (GEJ) cancer who may benefit from a targeted treatment option. CLDN18.2 is an emerging biomarker in gastric and GEJ cancers and helps predict the likelihood of response to targeted therapy. As the leader in companion diagnostics, Roche continues to build on its commitment to improve personalised healthcare to enable better patient outcomes. TUCSON, Ariz., Oct. 18, 2024 /PRNewswire/ -- Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the VENTANA Ⓡ CLDN18 (43-14A) RxDx Assay is the first U.S. Food and Drug Administration (FDA) approved immunohistochemistry (IHC) companion diagnostic for determining CLDN18 protein expression in tumours of patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma. These patients now may be eligible for treatment with Astellas' targeted therapy VYLOY TM (zolbetuximab). "Patients who are diagnosed with gastric or gastroesophageal junction cancer are often diagnosed in an advanced stage as early symptoms can be similar across several conditions," said Jill German, Head of Pathology Lab at Roche Diagnostics. "Our companion diagnostic for CLDN18 can help identify patients eligible for targeted treatment and provide them with additional therapeutic options. With the launch of this test, Roche continues to advance personalised healthcare by expanding our innovative companion diagnostic portfolio." Current guidelines for gastric/GEJ cancer recommend using biomarkers to guide therapeutic decision making. The new VENTANA CLDN18 (43-14A) RxDx Assay can help determine CLDN18.2 status and inform clinicians about the likelihood of patients benefiting from CLDN18.2 targeted therapy. VYLOY is the first FDA-approved treatment specifically targeting HER2-negative locally advanced unresectable or metastatic gastric or GEJ cancer patients whose tumours are CLDN18.2-positive. Gastric cancer is the fifth most common cancer and the fourth leading cause of cancer deaths worldwide.1 In the U.S., 62% of gastric/GEJ cancer cases are advanced when initially diagnosed, contributing to a five-year overall survival rate of only 6%.2,3 Although gastric/GEJ cancer is less prevalent in the U.S. than in other parts of the world, it is often diagnosed late as signs and symptoms are common to other conditions.4 About the VENTANA CLDN18 (43-14A) RxDx Assay The VENTANA CLDN18 (43-14A) RxDx Assay is a qualitative immunohistochemical assay intended to be used in the assessment of Claudin 18 (CLDN18) protein in gastric adenocarcinoma including gastroesophageal junction (GEJ) adenocarcinoma. The OptiView DAB IHC Detection Kit is used for staining on a BenchMark ULTRA instrument. The assay is indicated as an aid in identifying patients with gastric or GEJ adenocarcinoma who may be eligible for treatment with VYLOY® (zolbetuximab) in accordance with the approved therapeutic product labelling. The Roche test measures expression of both variants of the CLDN18 protein (18.1 and 18.2 isoforms). CLDN18.2 is the predominant variant expressed in gastric and GEJ cancers.5,6 The approval of the VENTANA CLDN18 (43-14A) RxDx Assay is based on the results of the SPOTLIGHT and GLOW clinical studies where it was used as the enrollment assay to identify patients whose tumours were CLDN18.2 positive. CLDN18.2 positivity is defined as ≥ 75% of tumour cells demonstrating moderate to strong membrane CLDN18 staining as measured by the VENTANA CLDN18 (43-14A) RxDx Assay. In these studies, approximately 38% of gastric/GEJ cancer patients expressed high levels of CLDN18 and were considered CLDN18.2 positive by the VENTANA CLDN18 (43-14A) RxDx Assay. Patients who received a combination of zolbetuximab and chemotherapy experienced a 25-31% reduction in disease progression or death.7,8 About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world's largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the fifteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit . All trademarks used or mentioned in this release are protected by law. References [1] Sung H et al. CA Cancer J Clin 2021;71:209-49. [2] ACS. Cancer Facts & Figures 2022. . Accessed 01-12-2022. [3] NCI SEER Cancer stat facts: stomach cancer. . Accessed 11-30-2023. [4] National Cancer Institute. Gastric Cancer Treatment (PDQ®)-Patient Version. Accessed at on March 8, 2023. [5] Saito, T. Matsuda, D. Moran, P-114 Claudin 18 isoform expression in gastric adenocarcinoma and pancreatic adenocarcinoma, Annals of Oncology, Volume 32, Supplement 3, 2021, Page S138, ISSN 0923-7534, . [6]VENTANA® CLDN18 (43-14A) RxDx Assay Package Insert, 2023 [7] Astellas press release, Astellas to Present Positive Findings from Phase 3 SPOTLIGHT Trial of Zolbetuximab during 2023 ASCO GI Cancers Symposium. . Accessed June 12, 2023. [8] Astellas press release, Astellas Announces Positive Findings from Phase 3 GLOW Trial of Zolbetuximab during March ASCO Plenary Series. . Accessed June 12, 2023. Roche Media Relations Jo Lynn Garing, 317-363-7286 [email protected] SOURCE Roche WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

FDA Headquarters, Grandbrothers/Getty Images The FDA’s Oncology Drugs Advisory Committee voted near-unanimously that the benefits of PD-1 inhibitors like Keytruda and Opdivo in PD-L1 low patients do not outweigh the risks. The FDA’s Oncology Drugs Advisory Committee voted Thursday to recommend the regulator narrow the label of blockbuster PD-1 inhibitors Keytruda, from Merck, and Opdivo and Yervoy, from Bristol Myers Squibb, in stomach and esophageal cancers. In the morning session, the panel of experts voted overwhelmingly—10-2, with one abstention—against the use of these drugs for the first-line treatment of advanced HER2-negative stomach cancer in patients with PD-L1 expression scores less than 1. Currently, Keytruda and Opdivo can be used in these patients regardless of their PD-L1 levels. Although the FDA will make the final call on label adjustments, many panelists indicated a belief that their votes would lead to this end. Merck, BMS, and BeiGene—which is developing the PD-1 blocker Tevimbra (tislelizumab) for this indication—participated in the meeting, along with physicians, patients and FDA representatives. Using data from studies supporting the approval of Keytruda and Opdivo for sttomach and esophageal cancers, as well as data submitted to support the potential approval of tislelizumab, the panelists discussed the value of PD-L1 expression as a predictive biomarker for determining potential benefit from immune checkpoint inhibitors (ICI) such as these, and the risk-benefit pro using them in people whose cancers have low PD-L1 expression. In briefing documents released ahead of the adcomm, FDA reviewers determined that high PD-L1 is likely a “predictive biomarker of treatment efficacy” in first-line gastric adenocarcinoma. There is “unclear” benefit in those with PD-L1 scores lower than 10, the reviewers wrote, and these drugs do not appear to have substantial benefit in patients with PD-L1 scores lower than 1. Thus, the broad use of PD-1 blockers “may not be in the best interest of patients with tumors with low PD-L1 expression.” Most panelists agreed with this assessment. “Clearly, having a high PD-L1 ligand measurement is associated with greater efficacy,” psychiatrist James Randolph Hillard, a patient representative on the panel who has battled stomach cancer, said in Thursday’s adcomm. But, he added, “I don’t think there’s clear evidence for the null hypothesis, that there’s no chance” ICIs will be valuable in treating people with scores less than 1. The FDA also noted in its briefing documents the potential risks of PD-1 inhibitors, including serious immune-related adverse events, and panelists agreed. Hanna Sanoff, gastrointestinal cancer section chief at the University of North Carolina at Chapel Hill, said during the adcomm that fatal toxicities have been seen with these drugs. “The folks we don’t have at the microphone are the folks who have passed away from getting PD-1 inhibitors.” Merck and BMS both argued in their briefing document to maintain the status quo, with BMS writing that the current labeling leaves the decision in the hands of the treating physician “and increases the chance for patients who may potentially benefit . . . to be considered for treatment.” However, Daniel Spratt, chairman and professor of radiation oncology at University Hospitals, Seidman Cancer Center and Case Western Reserve University, who voted no, pointed out that physicians see very few low PD-L1 patients. “The average doctor sees five of these a year, so I’m just not sure we want to let their doctor make this decision,” he said during the adcomm, noting the financial and toxicity impacts for these patients if they are given PD-1 inhibitors. Hillard, who voted yes, noted that differing PD-L1 assays pose a challenge. “It’s clear that there’s some variability in terms of how this is assessed in different settings.” After morning voting was completed, ODAC Director Richard Pazdur put out a call to the three pharma companies present for harmonization among PD-L1 assays. “It’s a rare opportunity that I get three drug companies in front of me simultaneously,” Pazdur quipped. Merck, BMS and BeiGene all signaled their support—though Pazdur repeated his appeal for their cooperation more than once during the meeting. Secondly, Pazdur asked if, in the event that the drugs’ labels are restricted to those with a PD-L1 score higher than 1, the companies would consider offering them free of charge in an expanded use program to patients with scores lower than 1. On this question, the companies were open but noncommittal. Esophageal Cancer Vote The afternoon session posed the same questions about the use of the same PD-1 inhibitors in esophageal squamous cell carcinoma, in addition to Yervoy. The panel voted 11-1 against, with one abstention, the use of PD-1 inhibitors in first-line unresectable or metastatic esophageal squamous cell carcinoma with low or no PD-L1 expression. Randy Hawkins, assistant professor of internal medicine at Charles R. Drew University of Medicine & Science, said he had “some apprehension about removing something that was available but could not ignore the numbers.” Throughout the day, committee members lauded the quality of the data presented. “Despite the small numbers, I think this is the best dataset we’re going to get,” Heidi McKean, GI medical oncology program director at Avera Cancer Institute, who voted with the majority, said following the afternoon vote. The lone dissenting vote came from patient representative Dana Deighton. “I understand the numbers, and I understand the concerns . . . but as a patient, I also had no options and had to fight for anything I could find,” she said. “And I do believe in the Hail Mary passes.”