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• First-in-human data for potential first-in-class anti-CEACAM5 ADC with topoisomerase 1 inhibitor payload, M9140, in treatment of metastatic colorectal cancer to be featured in oral presentation
• Phase I data for tuvusertib, lead asset from the company?s unique portfolio of DDR inhibitors, including an oral presentation on the combination with a PARP inhibitor, support further clinical development
• New analyses contribute to totality of evidence supporting BAVENCIO first-line maintenance as a standard-of-care in advanced bladder cancer

Not intended for Canada-, UK- or US-based media

DARMSTADT, Germany --(BUSINESS WIRE)-- 23.05.2024 --

Merck, a leading science and technology company, today announced new research from the company?s diverse oncology portfolio will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, May 31 to June 4, Chicago. Data from company- and investigator-sponsored studies include 31 accepted abstracts across more than 10 tumor types, including seven oral presentations, highlighting the company?s innovative oncology pipeline encompassing potential first-in-class approaches designed to hit cancer at its core.

?Our research at the 2024 ASCO Annual Meeting showcases the advancement of our novel pipeline designed to exploit the major vulnerabilities of cancer, with new data from our lead investigational antibody-drug conjugate and our DNA damage response portfolio,? said Victoria Zazulina, M.D., Head of Development Unit, Oncology, for the Healthcare business of Merck. ?In addition, new analyses from pivotal studies and collaborations underline our determination to maximize the impact of our standard-of-care treatments as we seek to improve the lives of those living with cancer.?

Highlights of the company?s data include:

First-in-human data for the antibody-drug conjugate (ADC) M9140 (Abstract 3000). This Phase I trial is investigating the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity of M9140, the company?s investigational ADC against carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) with a novel exatecan payload, in heavily pretreated patients with metastatic colorectal cancer. Data from 40 patients treated across seven dose levels in Part 1A of the study showed encouraging clinical activity and a manageable and predictable safety profile in this population. The randomized dose-expansion part of the study is ongoing.

New findings for tuvusertib, the lead oral ATRi asset from the company?s portfolio of DNA damage response (DDR) inhibitors (Abstracts 3018, 2612, 2614). Data from the DDRiver? Clinical Trials program highlight the potential of the investigational oral ataxia telangiectasia and RAD3-related inhibitor (ATRi) tuvusertib in various combinations across solid tumors.

• Part B1 of the Phase I DDRiver Solid Tumors 301 study assessed safety as well as PK, pharmacodynamics, and preliminary efficacy of different dosing regimens of tuvusertib in combination with the poly-ADP ribose polymerase (PARP) inhibitor niraparib in patients with locally advanced or metastatic unresectable solid tumors refractory to standard treatment. Data show a manageable safety profile and preliminary efficacy in patients with advanced solid tumors, confirming suitability of this combination for further evaluation.
• Presentations from the Phase Ib DDRiver Solid Tumors 320 study showcase further data on the combination of tuvusertib with the company?s ataxia telangiectasia-mutated (ATM) inhibitor lartesertib, building on the safety and efficacy data presented at the AACR Annual Meeting in April 2024, and for the first time, with the company?s immune checkpoint inhibitor BAVENCIO^® (avelumab). The findings further support that both DDRi assets are well-positioned for combination development building on in-house expertise.

Post-hoc independent read confirmation of Phase II efficacy data for xevinapant (Abstract e18039). A previously published Phase II study of the investigational oral IAP (inhibitor of apoptosis protein) inhibitor xevinapant plus chemoradiotherapy (CRT) versus placebo plus CRT in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) showed improved efficacy outcomes. This post-hoc analysis showed consistent outcomes when comparing the review of selected efficacy endpoints by blinded independent review committee (BIRC) with previously reported outcomes by investigator review. Xevinapant plus CRT demonstrated a 62% reduction in the risk of disease progression (by BIRC) or death compared with placebo plus CRT, with prolonged duration of response and increased complete response rates.

Long-term efficacy and safety analyses from JAVELIN Bladder 100 (Abstracts 4566, 4567). New analyses of this Phase III study, which has previously shown in a post-hoc exploratory analysis a median overall survival of 29.7 months in patients who received BAVENCIO plus best supportive care (BSC) as measured from the start of first-line chemotherapy, confirm the benefit of BAVENCIO first-line maintenance in key subgroups of patients with advanced urothelial carcinoma that has not progressed on platinum-based chemotherapy, including those who have low tumor burden and in those with mixed histologic subtypes. These findings further support the use of the JAVELIN Bladder regimen as a standard of care in this setting and as an important first-line treatment regimen for patients with low tumor burden in particular, where pronounced efficacy with BAVENCIO (vs BSC alone) was observed.

Health-related quality-of-life data for TEPMETKO^® (tepotinib) in NSCLC (Abstract 8575). This analysis reports health-related quality of life (HRQoL) outcomes from the Phase II VISION study of TEPMETKO in patients with metastatic non-small cell lung cancer (NSCLC) harboring METex14 skipping alterations with brain, liver, adrenal or bone metastases. These patients experienced stable HRQoL during treatment with TEPMETKO, with trends for improvement in cough, consistent with results for the overall population.

Additional company-sponsored activity at ASCO:

Medical Evening Lecture

What's new in LA SCCHN? An evasive enemy and an evolving landscape

Faculty: Kevin Harrington (chair), Institute of Cancer Research, UK; Ari Rosenberg, University of Chicago Medicine, USA; Jonathan Schoenfeld, Dana-Farber Cancer Institute, USA; Sue Yom, University of California, San Francisco, USA

June 2, 2024, 7:00PM-8:00PM CDT

W Chicago City Center hotel (172 West Adams Street), Great Room I

Select Merck-related abstracts accepted for the ASCO 2024 Annual Meeting include (all times in CDT):

Advancing the Future of Cancer Care

At Merck, we strive every day to improve the futures of people living with cancer. Our research explores the full potential of promising mechanisms in cancer research, focused on synergistic approaches designed to hit cancer at its core. We are determined to maximize the impact of our standard-of-care treatments and to continue pioneering novel medicines. Our vision is to create a world where more cancer patients will become cancer survivors. Learn more at www.merckgrouponcology.com.

About M9140

M9140 is an investigational anti-CEACAM5 antibody-drug conjugate (ADC). Leveraging the company?s novel linker-payload technology, M9140 is the first CEACAM5 ADC with an exatecan payload, a potent topoisomerase inhibitor (TOP1i), which has been rationally designed for stability in circulation and superior cancer cell killing activity. Beyond the direct effect on the target cell, M9140 has been shown in preclinical research to induce tumor cell death through a bystander effect permeating the cell membrane to neighboring cells, inducing apoptosis (cell death). This bystander effect within the tumor microenvironment may enhance efficacy, particularly in tumors with heterogenous CEACAM5 expression. M9140 is currently being investigated in advanced solid tumors in a first-in-human, Phase I dose-escalation clinical trial (NCT05464030).

About Tuvusertib

Tuvusertib (M1774), is the lead asset in the company?s portfolio of DNA damage response inhibitors. Tuvusertib is an investigational, potentially best-in-class small-molecule oral inhibitor of the ataxia telangiectasia and Rad3-related (ATR) kinase, which serves as a major regulator of the replication stress response. Early clinical data for tuvusertib have shown potency, selectivity, and the potential to achieve high therapeutic doses without rate-limiting side effects. The company?s DDRiver? Clinical Trial Program is exploring the potential of tuvusertib as a backbone therapy in a variety of combinations with other DDR inhibitors, immune checkpoint inhibitors, or cytotoxic agents, touching on multiple clinical hypotheses across several types of cancer.

About Xevinapant

Xevinapant (formerly known as Debio 1143) is an investigational first-in-class potent oral small-molecule IAP (inhibitor of apoptosis protein) inhibitor developed for the treatment of LA SCCHN, with a proposed dual mechanism of action: xevinapant releases the brakes on apoptosis and increases anti-tumor immunity, re-initiating the programmed cell death of tumor cells. Via this dual mechanism, xevinapant is thought to enhance the effects of chemo- and radiotherapy. Xevinapant has demonstrated improved efficacy outcomes in combination with chemoradiotherapy (CRT), including 18-month locoregional control, three-year progression-free survival and five-year survival, compared with placebo plus CRT in a Phase II study in patients with unresected LA SCCHN. Xevinapant is being studied in two Phase III studies: TrilynX?, in patients with unresected LA SCCHN, and XRay Vision?, in patients with resected LA SCCHN who are at a high risk of recurrence and who are deemed cisplatin-ineligible. In March 2021, Merck gained exclusive rights from Debiopharm to develop and commercialize xevinapant worldwide. Xevinapant is not approved for any use anywhere in the world.

About BAVENCIO^® (avelumab)

BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.

BAVENCIO Approved Indications

The European Commission (EC) has authorized the use of BAVENCIO as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum-based chemotherapy. BAVENCIO in combination with axitinib is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). BAVENCIO is also authorized by the EC for use as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC).

In the US, BAVENCIO is indicated for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. BAVENCIO is also indicated for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

BAVENCIO in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced RCC. Additionally, the US Food and Drug Administration (FDA) has approved BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic MCC.

BAVENCIO is currently approved for at least one indication for patients in more than 50 countries.

BAVENCIO Safety Profile from the EU Summary of Product Characteristics (SmPC)

The special warnings and precautions for use for BAVENCIO monotherapy include infusion-related reactions, as well as immune-related adverse reactions that include pneumonitis and hepatitis (including fatal cases), colitis, pancreatitis (including fatal cases), myocarditis (including fatal cases), endocrinopathies, nephritis and renal dysfunction, and other immune-related adverse reactions. The special warnings and precautions for use for BAVENCIO in combination with axitinib include hepatotoxicity.

The SmPC list of the most common adverse reactions with BAVENCIO monotherapy in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, weight decreased and vomiting. The list of most common adverse reactions with BAVENCIO in combination with axitinib includes diarrhea, hypertension, fatigue, nausea, dysphonia, decreased appetite, hypothyroidism, cough, headache, dyspnea, and arthralgia.

About TEPMETKO^® (tepotinib)

TEPMETKO is a once-daily oral MET inhibitor that inhibits the oncogenic MET receptor signaling caused by MET (gene) alterations. Discovered and developed in-house at Merck, TEPMETKO has a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.

TEPMETKO is the first oral MET inhibitor to have received a regulatory approval anywhere in the world for the treatment of advanced non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations, with its approval in Japan in March 2020. In February 2024, the US Food and Drug Administration granted full approval for TEPMETKO. The conversion from accelerated approval, which the company received in February 2021, to full FDA approval is based on additional data from the ongoing Phase II VISION study, the largest trial of its kind. The updated label includes revised data for overall response rate and duration of response, as well as safety outcomes for more than 300 patients who were treated with TEPMETKO once-daily for metastatic NSCLC with METex14 skipping alterations.

TEPMETKO is available in a number of countries. To meet an urgent clinical need, TEPMETKO is also available in a pilot zone of China in line with the government policy to drive early access for innovative medicines approved outside of China.

TEPMETKO Safety Profile from the EU Summary of Product Characteristics (SmPC)

The special warnings and precautions for use for TEPMETKO monotherapy include Interstitial lung disease (ILD) or ILD-like adverse reactions including pneumonitis, increase of liver enzymes (ALT and AST), QTc prolongation, and embryo-fetal toxicity.

The most common adverse reactions in ? 20% of exposed to tepotinib at the recommended dose in the target indication are oedema, mainly peripheral oedema, nausea, hypoalbuminemia, diarrhea and increase in creatinine. The most common serious adverse reactions in ? 1% of patients are peripheral oedema, generalized oedema and ILD.

About ERBITUX^® (cetuximab)

ERBITUX is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of ERBITUX is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth. Based on in vitro evidence, ERBITUX also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody-dependent cell-mediated cytotoxicity [ADCC]).

ERBITUX has already obtained market authorization in over 100 countries worldwide for the treatment of RAS wild-type metastatic colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck. Merck licensed the right to market ERBITUX, a registered trademark of ImClone LLC, outside the U.S. and Canada from ImClone LLC, a wholly owned subsidiary of Eli Lilly and Company, in 1998.

About Merck

Merck, a leading science and technology company, operates across life science, healthcare and electronics. Around 63,000 employees work to make a positive difference to millions of people?s lives every day by creating more joyful and sustainable ways to live. From providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices ? the company is everywhere. In 2023, Merck generated sales of € 21 billion in 65 countries.

Scientific exploration and responsible entrepreneurship have been key to Merck?s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as MilliporeSigma in life science, EMD Serono in healthcare, and EMD Electronics in electronics.

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