EMD Serono to Showcase Advances in the Science of Cancer With New Data Presented at ASCO 2024

• 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 UK-based media

ROCKLAND, Mass.–(BUSINESS WIRE)–EMD Serono, the Healthcare business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada, 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 KGaA, Darmstadt, Germany. “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 KGaA, Darmstadt, Germany-related abstracts accepted for the ASCO 2024 Annual Meeting include (all times in CDT):

Advancing the Future of Cancer Care

At EMD Serono, 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.emdseronooncology.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 KGaA, Darmstadt, Germany, 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

BAVENCIO^® (avelumab) is indicated in the US 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 renal cell carcinoma (RCC).

In the US, BAVENCIO is indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC).

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

BAVENCIO Important Safety Information from the US FDA-Approved Label

BAVENCIO can cause severe and fatal immune-mediated adverse reactions in any organ system or tissue and at any time after starting treatment with a PD-1/PD-L1 blocking antibody, including after discontinuation of treatment.

Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

No dose reduction for BAVENCIO is recommended. For immune-mediated adverse reactions, withhold or permanently discontinue BAVENCIO depending on severity. In general, withhold BAVENCIO for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue BAVENCIO for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating corticosteroids. In general, if BAVENCIO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic corticosteroids (eg, endocrinopathies and dermatologic reactions) are discussed in subsequent sections.

BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for Grade 2 and permanently discontinue for Grade 3 or Grade 4 pneumonitis. Immune-mediated pneumonitis occurred in 1.2% (21/1738) of patients, including fatal (0.1%), Grade 4 (0.1%), Grade 3 (0.3%) and Grade 2 (0.6%) adverse reactions. Systemic corticosteroids were required in all (21/21) patients with pneumonitis.

BAVENCIO can cause immune-mediated colitis. The primary component of immune-mediated colitis consisted of diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Withhold BAVENCIO for Grade 2 or Grade 3, and permanently discontinue for Grade 4 colitis. Immune-mediated colitis occurred in 1.5% (26/1738) of patients, including Grade 3 (0.4%) and Grade 2 (0.7%) adverse reactions. Systemic corticosteroids were required in all (26/26) patients with colitis.

BAVENCIO can cause hepatotoxicity and immune-mediated hepatitis. Withhold or permanently discontinue BAVENCIO based on tumor involvement of the liver and severity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation. Immune-mediated hepatitis occurred with BAVENCIO as a single agent in 0.9% (16/1738) of patients, including fatal (0.1%), Grade 3 (0.6%), and Grade 2 (0.1%) adverse reactions. Systemic corticosteroids were required in all (16/16) patients with hepatitis.

BAVENCIO in combination with axitinib can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 ALT and AST elevation compared to BAVENCIO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used as monotherapy. Withhold or permanently discontinue both BAVENCIO and axitinib based on severity of AST, ALT, or total bilirubin elevation, and consider administering corticosteroids as needed. Consider rechallenge with BAVENCIO or axitinib, or sequential rechallenge with both BAVENCIO and axitinib, after recovery. In patients treated with BAVENCIO in combination with axitinib in the advanced RCC trials, increased ALT and increased AST were reported in 9% (Grade 3) and 7% (Grade 4) of patients. Immune-mediated hepatitis was reported in 7% of patients including 4.9% with Grade 3 or 4 immune-mediated hepatitis. Thirty-four patients were treated with corticosteroids and one patient was treated with a non-steroidal immunosuppressant.

BAVENCIO can cause primary or secondary immune-mediated adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement, as clinically indicated. Withhold BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated adrenal insufficiency occurred in 0.5% (8/1738) of patients, including Grade 3 (0.1%) and Grade 2 (0.3%) adverse reactions. Systemic corticosteroids were required in all (8/8) patients with adrenal insufficiency.

BAVENCIO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement, as clinically indicated. Withhold BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated pituitary disorders occurred in 0.1% (1/1738) of patients, which was a Grade 2 (0.1%) adverse reaction.

BAVENCIO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism, as clinically indicated. Withhold BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Thyroiditis occurred in 0.2% (4/1738) of patients, including Grade 2 (0.1%) adverse reactions. Hyperthyroidism occurred in 0.4% (7/1738) of patients, including Grade 2 (0.3%) adverse reactions. Systemic corticosteroids were required in 29% (2/7) of patients with hyperthyroidism. Hypothyroidism occurred in 5% (90/1738) of patients, including Grade 3 (0.2%) and Grade 2 (3.7%) adverse reactions. Systemic corticosteroids were required in 7% (6/90) of patients with hypothyroidism.

BAVENCIO can cause immune-mediated type I diabetes mellitus, which can present with diabetic ketoacidosis. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated type I diabetes mellitus occurred in 0.1% (2/1738) of patients, including Grade 3 (0.1%) adverse reactions.

BAVENCIO can cause immune-mediated nephritis with renal dysfunction. Withhold BAVENCIO for Grade 2 or Grade 3, and permanently discontinue for Grade 4 increased blood creatinine. Immune-mediated nephritis with renal dysfunction occurred in 0.1% (1/1738) of patients, which was a Grade 2 (0.1%) adverse reaction. Systemic corticosteroids were required in this patient.

BAVENCIO can cause immune-mediated dermatologic adverse reactions, including rash or dermatitis. Exfoliative dermatitis including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold BAVENCIO for suspected and permanently discontinue for confirmed SJS, TEN, or DRESS. Immune-mediated dermatologic adverse reactions occurred in 5% (90/1738) of patients, including Grade 3 (0.

Contacts

Media Relations
noelle.piscitelli@emdserono.com
Phone: +1 (781) 427-4351

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