Sunday, May 23, 2021

Data from Merck’s Oncology Portfolio Highlight Significant Advances in Cancer Care at ASCO21

  DARMSTADT, Germany -Saturday 22 May 2021 [ AETOS Wire ]

  • New analyses from pivotal BAVENCIO® study reinforce unique clinical benefits across different subgroups in the treatment of advanced urothelial carcinoma
  • New data from VISION study of TEPMETKO® show association between liquid biopsy-identified biomarker and clinical response in METex14 skipping NSCLC, supporting liquid biopsy as a means for monitoring treatment response
  • TEPMETKO® shows efficacy in METex14 skipping NSCLC patients with brain metastases consistent with overall treatment population
  • Oral presentations from independent studies reinforce the position of ERBITUX® in 1L RAS wt mCRC and as backbone of treatment in SCCHN

(BUSINESS WIRE)-- Not intended for UK-, US- or Canada-based media

Merck, a leading science and technology company, today announced 40 abstracts, including seven oral presentations and seven poster discussions, from Company- and investigator-sponsored studies (ISS) and external collaborations, representing the Company’s innovative oncology portfolio will be presented at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, June 4-8, 2021.

“Important new analyses from our pivotal studies in urothelial cancer and non-small cell lung cancer, which have led to recent regulatory approvals for BAVENCIO® (avelumab) and TEPMETKO® (tepotinib) in these tumor types, demonstrate how our research continues to drive forward new standards of care in certain cancers with high unmet medical need,” said Danny Bar-Zohar, Global Head of Development for the Healthcare business of Merck. “These analyses, along with additional data informing the understanding of new and emerging mechanisms under investigation, are the latest examples of our dedication to advancing the science of cancer treatment to make a meaningful difference for patients.”

The Company’s research programs, focused on synergistic approaches in immuno-oncology, oncogenic pathways, and DNA damage response (DDR), aim to tackle some of the most challenging tumor types, including urothelial cancer (UC), non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), colorectal cancer (CRC), and cervical cancer (CC).

Key Data Highlights at ASCO

BAVENCIO (avelumab)
Data across three approved indications for BAVENCIO (avelumab) provide further evidence of continued patient benefit:

  • Advanced urothelial cancer (presentations: 4520, 4525, 4527). New analyses from the Phase III JAVELIN Bladder 100 study demonstrated consistent survival benefit of BAVENCIO (avelumab) as first-line maintenance treatment across key subgroups including those defined by the treatment-free interval from the end of chemotherapy to the start of maintenance, disease stage, site of metastasis, or genomic subtype. These data further reinforce the role of BAVENCIO for patients with advanced UC that have not progressed on 1L platinum-containing chemotherapy.
  • Advanced renal cell carcinoma (aRCC) (presentations: 4514, 4574). Data from the extended follow-up of the Phase III JAVELIN Renal 101 study explored the effects of subsequent therapies on outcomes for patients with aRCC treated with BAVENCIO (avelumab) plus axitinib and confirmed the efficacy benefits of the combination across International Metastatic RCC Data Consortium (IMDC) risk groups including in the favorable risk group.
  • Metastatic Merkel cell carcinoma (mMCC) (presentation: 9517). In previously treated patients with metastatic MCC (mMCC), treatment with BAVENCIO (avelumab) provided meaningful long-term overall survival (OS), based on more than five years of follow-up in Part A of the Phase II JAVELIN Merkel 200 study with 48- and 60-month OS rates 30% (95% CI, 20%-40%) and 26% (95% CI, 17%-36%), respectively. These results further support the role of avelumab as a standard-of-care treatment for patients with mMCC.

TEPMETKO (tepotinib)
ASCO highlights for TEPMETKO (tepotinib) include new data from the Phase II VISION study:

  • METex14 NSCLC biomarker response detected in liquid biopsy (LBx) abstract (oral presentation: 9012). In this analysis, reduction in variant allele frequency following tepotinib treatment was related to an improved treatment outcome. Further, this investigation provides evidence that liquid biopsy may provide a reliable means for monitoring response to treatment, understanding resistance mechanisms, and improving patient outcomes and quality of life.
  • METex14 skipping NSCLC with brain metastases (presentation: 9084). Data demonstrated efficacy in patients with mesenchymal epithelial transition (MET) exon 14 (METex14) skipping NSCLC with brain metastases consistent with the overall treatment population, complemented by intracranial activity in an ad hoc retrospective analysis of brain lesions determined by CT/MRI. Brain metastases are reported in 20% to 40% of patients with METex14 skipping NSCLC and are associated with poor prognosis.
  • NSCLC with MET amplification (METamp) (presentation: 9021). Clinical activity observed in VISION Cohort B, the first study of a MET inhibitor in people with NSCLC with METamp prospectively detected by liquid biopsy, showed the potential of tepotinib to target METamp-driven disease, particularly in the treatment-naïve setting where there is high unmet need. MET amplification is a genetic alteration occurring in approximately 1% to 5% of patients with NSCLC and has no approved targeted therapies.

Tepotinib is also being investigated in two ongoing studies, which are currently recruiting patients: INSIGHT 2 (Presentation: TPS9136), assessing the combination of osimertinib and tepotinib in patients with epithelial growth factor receptor (EGFR)-mutant NSCLC that has developed resistance to first-line osimertinib treatment due to MET amplification; and PERSPECTIVE (Presentation: TPS3616), evaluating tepotinib in combination with cetuximab in mCRC having acquired resistance to anti-EGFR antibody-targeted therapy due to MET amplification.

ERBITUX® (cetuximab)
For the Company’s first biology-driven leader, ERBITUX (cetuximab), a number of ISS, and the PERSPECTIVE study in combination with TEPMETKO (tepotinib) continue to demonstrate its steady role across the continuum of care in metastatic colorectal cancer, and as a backbone of treatment in squamous cell carcinoma of the head and neck.

  • DEEPER “JACCRO CC-13” (oral presentation: 3501). Significant greater depth of response seen with cetuximab + triplet CT vs bevacizumab + triplet CT in 1L RAS wt mCRC
  • FIRE 4.5 “AIO KRK-0116” (oral presentation: 3502). Comparable efficacy shown between cetuximab and bevacizumab in 1L BRAF mt mCRC
  • TROG 12.01 and De-ESCALaTE (oral presentation: 109). This pooled analysis from two Phase III studies identifies a potential prognostic biomarker for patients treated with cetuximab + RT in HPV-positive oropharyngeal cancer (OPC) LA SCCHN

Bintrafusp alfa (M7824)
Data for bintrafusp alfa, an investigational bifunctional fusion protein, continue to shed light on the potential benefits of dual inhibition of the TGF-β and PD-L1 pathways:

  • Recurrent/metastatic cervical cancer (oral presentation: 5509). A pooled analysis of data from the Phase I INTR@PID Solid Tumor 001 study and a National Cancer Institute (NCI)-led Phase II study demonstrated that bintrafusp alfa monotherapy has a manageable safety profile and clinical activity in patients with platinum-pretreated, immune checkpoint inhibitor-naïve recurrent/metastatic cervical cancer.
  • HPV 16+ advanced malignancies (oral presentation: 2501). Data from this NCI-led Phase II clinical study of patients with advanced HPV 16+ cancers provided early evidence of the clinical activity of a triple combination of bintrafusp alfa, NHS-IL12 and PDS0101, with a manageable safety profile.

Merck is a science-led organization dedicated to delivering transformative medicines with the goal of making a meaningful difference in the lives of people affected by cancer. Our oncology research efforts aim to leverage our synergistic portfolio in oncogenic pathways, immuno-oncology, and DNA Damage Response (DDR) to tackle challenging tumor types in gastrointestinal, genitourinary, and thoracic cancers. Our curiosity drives our pursuit of treatments for even the most complex cancers, as we work to illuminate a path to scientific breakthroughs that transform patient outcomes. Learn more at https://www.merckgrouponcology.com.

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. In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

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) granted accelerated approval for BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic MCC. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

BAVENCIO is currently approved for patients in 50 countries for at least one use.

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 an oral MET inhibitor that inhibits the oncogenic MET receptor signaling caused by MET (gene) alterations. Discovered and developed in-house at Merck KGaA, Darmstadt, Germany, 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 was the first oral MET inhibitor to receive a regulatory approval anywhere in the world for the treatment of advanced NSCLC harboring MET gene alterations, with its approval in Japan in March 2020. TEPMETKO was approved in the United States in February 2021 for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Tepotinib is currently under clinical investigation and not yet approved in any markets outside of Japan and the United States.

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 Bintrafusp Alfa
Bintrafusp alfa (M7824), discovered in-house at Merck, and currently in clinical development through a strategic alliance with GSK, is a potential first-in-class investigational bifunctional fusion protein designed to simultaneously block two immunosuppressive pathways, TGF-β and PD-L1, within the tumor microenvironment. This bifunctional approach is thought to control tumor growth by potentially restoring and enhancing anti-tumor responses. In preclinical studies, bintrafusp alfa has demonstrated antitumor activity both as monotherapy and in combination with chemotherapy. Based on its mechanism of action, bintrafusp alfa offers a potential targeted approach to addressing the underlying pathophysiology of difficult-to-treat cancers.

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About Merck
Merck, a leading science and technology company, operates across healthcare, life science and electronics. Around 58,000 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 advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2020, Merck generated sales of € 17.5 billion in 66 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 EMD Serono in healthcare, MilliporeSigma in life science, and EMD Electronics.

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