Business Wire

Merck Advances ATR Inhibitor Berzosertib in Small Cell Lung Cancer With New Published Data and Initiation of Phase II Trial With Registrational Intent

Share

Merck, a leading science and technology company, today announced key clinical advancements for berzosertib (M6620), an investigational, potent and selective ataxia telangiectasia and Rad3-related (ATR) inhibitor. Berzosertib is the leading asset in the company’s DNA damage response (DDR) inhibitor program and one of the most advanced ATR inhibitors in oncology clinical development industry-wide.

Results from a Phase II proof-of-concept study conducted by the US National Cancer Institute (NCI) (NCT02487095)* and published in Cancer Cell showed that berzosertib in combination with the chemotherapy topotecan resulted in an objective response rate (ORR) of 36% among patients with relapsed small cell lung cancer (SCLC), including durable responses among a majority of responding patients with platinum-resistant disease.1 The NCI is also conducting a separate Phase II trial of berzosertib in combination with topotecan versus topotecan monotherapy in SCLC that has relapsed (NCT03896503)* which is currently the only randomized controlled trial of the combination in this population.

Merck also initiated a global Phase II study to further assess berzosertib in combination with topotecan for the treatment of relapsed, platinum-resistant SCLC (DDRiver SCLC 250). The first patient has been enrolled in the open-label, single-arm trial, which plans to include approximately 80 participants at about 41 study sites across Asia, Europe, and North America.

“Small-cell neuroendocrine cancers, including small cell lung cancer, are associated with very poor prognoses, and are a major clinical challenge with no effective therapeutic options. In this study, the combination of berzosertib and topotecan showed higher than expected response rates and durable responses in patients with platinum-resistant SCLC, highlighting the therapeutic potential of this combination for patients with this recalcitrant cancer type,” said Anish Thomas, MBBS, M.D., investigator and NIH Lasker Clinical Research Scholar at the Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, and lead investigator of the study. Dr. Thomas is collaborating with Merck KGaA, Darmstadt, Germany through a Cooperative Research and Development Agreement (CRADA).

Topotecan is the chemotherapeutic standard-of-care for second-line treatment of SCLC and is associated with low response rates, particularly in platinum-resistant disease.1 Findings from the NCI study highlight the vulnerability of SCLC tumors to ATR inhibition as a result of high levels of replication stress and the potential for the combination of berzosertib and topotecan to enhance the efficacy of topotecan among chemotherapy-resistant patients.1 These data build on earlier published results from Phase I of this study which also suggested a potential benefit of this combination in participants with platinum-resistant SCLC.2

“We are encouraged by these promising results, and are eager to further investigate berzosertib in a potentially registrational trial in SCLC as part of our front-running leadership in the research of DNA damage response,” said Danny Bar-Zohar, M.D., Global Head of Development for the Healthcare business sector of Merck.

These results are in addition to results from an NCI-sponsored open-label, randomized, Phase II study (NCI protocol 9944) evaluating berzosertib in combination with gemcitabine versus gemcitabine alone for the treatment of recurrent, platinum-resistant high-grade serous ovarian cancer, which were published in The Lancet Oncology in 2020. The study, conducted through a separate CRADA between NCI and Merck KGaA, Darmstadt, Germany, showed a benefit of adding berzosertib to gemcitabine in this treatment setting including improvement in progression-free survival, and is the first randomized study of an ATR inhibitor in any tumor type.3

As part of its new DDRiver™ Clinical Trials program, the company is investigating DDR inhibitor targeting pathways across more than ten trials in various tumor types.

NCI Study Results

In the Phase II single-arm study of berzosertib plus topotecan in patients with SCLC whose disease had progressed on prior therapy, 25 patients were evaluable for the primary endpoint of ORR as measured by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and the secondary endpoints of progression-free survival (PFS) and overall survival (OS) and duration of response (DOR). Berzosertib 210 mg/m2 was administered intravenously on days 2 and 5, and topotecan 1.25 mg/m2 was given intravenously on days 1 through 5 in 21-day cycles; treatment continued until disease progression.1

The confirmed ORR was 36% (95% CI, 18.0–57.5; all partial response).1 Most patients (68.0%) experienced tumor regressions.1 Responses were observed in patients with both platinum-sensitive (60.0% [95% CI, 14.7–94.7]) and platinum-resistant (30.0% [95% CI, 11.9–54.3]) disease.1 Median DOR was 6.4 months (95% CI, 1.1–14.3), and four of the six (66.7%) responders with platinum-resistant SCLC had DOR of more than 6 months.1 Median PFS was 4.8 months (95% CI, 2.8–7.4), with PFS rates at 4 months and 6 months of 60.0% (95% CI, 38.4-76.1) and 36.0% (95% CI, 18.2–54.2).1 Median OS was 8.5 months (95% CI, 5.6-13.6);1 OS rates at 6 months and 12 months were 68.0% (95% CI, 46.1–82.5) and 32.0% (95% CI, 15.2–50.2).1

Among 26 patients evaluable for safety, the most common treatment-related adverse events (AE) were anemia (96.2%), lymphopenia (96.2%), thrombocytopenia (92.3%), and neutropenia (50.0%), nausea (50.0%) and vomiting (42.3%).1 The most common grade 3 or 4 AEs were lymphopenia (69.2%), thrombocytopenia (57.7%), anemia (53.8%), and neutropenia (15.4%).1 No treatment-related deaths occurred.1 Most AEs were attributable to topotecan, which as monotherapy is associated with a high frequency of myelosuppression.1,4

*Additional information on these clinical trials are available at clinicaltrials.gov, through identifier numbers NCT02487095 and NCT03896503. Patients interested in enrolling in these berzosertib and topotecan combination clinical trials can call the National Cancer Institute’s toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615).

About Small Cell Lung Cancer

Of the estimated 1.6 million new lung cancer cases diagnosed worldwide each year, approximately 15% are SCLC.5 SCLC is the most aggressive form of lung cancer, characterized by a rapid doubling time and widespread metastases,6 and approximately two-thirds of patients present with extensive disease that has metastasized, when first found.7 The median survival time for patients with SCLC is 7 months,5 and the relative five-year survival rate is just 7%.8

About Berzosertib

Berzosertib is an investigational, potent and selective inhibitor of the ataxia telangiectasia and Rad3-related (ATR) protein that blocks ATR activity in cells. Berzosertib is the first ATR inhibitor evaluated in a randomized clinical trial in any tumor type,3 and it is the lead candidate in Merck’s DNA Damage Response (DDR) inhibitor portfolio. It is currently being investigated in a number of internal and external studies with early phase I/II data in small cell lung cancer, ovarian cancer, and various solid tumors.3,9 Berzosertib, formerly known as VX-970, was licensed from Vertex Pharmaceuticals in 2017. Berzosertib is not approved for any use anywhere in the world.

References

  1. Thomas A, Takahashi N, Rajapakse V, et al. Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress. Cancer Cell 39, (4), 2021, pp.566-579.
  2. Thomas, A., Redon, C. E., Sciuto, L., Padiernos, E., Ji, J., Lee, M. J., Yuno, A., Lee, S., Zhang, Y., Tran, L., et al. (2018). Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumors. J Clin Oncol 36, 1594-1602.
  3. Konstantinopoulos PA, et al. Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020 Jul;21(7):957-968. doi: 10.1016/S1470-2045(20)30180-7. Epub 2020 Jun 15. PMID: 32553118.
  4. von Pawel, J., Schiller, J. H., Shepherd, F. A., Fields, S. Z., Kleisbauer, J. P., Chrysson, N. G., Stewart, D. J., Clark, P. I., Palmer, M. C., Depierre, A., et al. (1999). Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17, 658-667.
  5. Wang S, et al. Survival changes in patients with small cell lung cancer and disparities between different sexes, socioeconomic statuses and ages. Sci Rep. 2017;(1):1339.
  6. Byers LA, Rudin CM. Small cell lung cancer: where do we go from here? Cancer. 2015;121(5):664-72.
  7. American Cancer Society. Small Cell Lung Cancer Stages. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/staging-sclc.html. (Accessed April 8, 2021).
  8. American Cancer Society. Lung Cancer Survival Rates. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html (Accessed April 8, 2021).
  9. Yap TA, et al. Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors. J Clin Oncol. 2020 Sep 20;38(27):3195-3204. doi: 10.1200/JCO.19.02404. Epub 2020 Jun 22. PMID: 32568634; PMCID: PMC7499606.

All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to http://www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

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.

To view this piece of content from cts.businesswire.com, please give your consent at the top of this page.

Contact information

Media Relations
Julissa Viana
julissa.viana@emdserono.com
Phone: +1 781 206 5795

About Business Wire

For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.

Subscribe to releases from Business Wire

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

Latest releases from Business Wire

EAG Expands Medical Device Testing Services with New Laboratory7.5.2021 18:22:00 EEST | Press release

EAG Laboratories is expanding its medical device testing capabilities with a new 20,000 square-foot laboratory located in St. Louis, Mo. The new laboratory is a bespoke design to support the requirements of the medical device industry. It increases EAG’s analytical capabilities, allows for improved turnaround times and helps meet evolving requirements from the FDA as well as the European Union Medical Device Regulations (MDR). Specialty features of the laboratory include: A cleanroom designed for particle isolation and identification A dedicated medical device polymer analysis laboratory State-of the-art instrumentation to support biocompatitility testing of ISO 10993-18 programs for medical devices and combination products EAG scientists have been investigating and resolving product failures for more than half a century and have a deep understanding of materials and testing procedures. The medical device laboratory expansion allows EAG to leverage that knowledge and apply it toward su

SoftServe Wins Learning and Development Honor at 2021 ATD Excellence in Practice Awards7.5.2021 14:00:00 EEST | Press release

SoftServe, a leading digital authority and consulting company, won the Excellence in Practice Award in the ‘Learning and Development’ category in the 2021 Association for Talent Development (ATD) Excellence in Practice Awards. SoftServe was recognized for its corporate learning hub, SoftServe University, which focuses on learning and development opportunities for associates, including the design and delivery of training. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210507005003/en/ Association for Talent Development logo. (Photo: Business Wire) “SoftServe is dedicated to creating a people-centric organization that allows associates to grow and develop professionally,” said Galyna Datsiv, AVP of Learning and Development at SoftServe. “Our corporate learning ecosystem within the integrated talent management framework enables us to reach SoftServe’s strategic business goals by ensuring associates are qualified and have the ex

 Monument Assurance Belgium and Intégrale Reach Agreement for the Transfer of Intégrale's Entire Portfolio and Staff to MAB7.5.2021 13:26:00 EEST | Press release

Monument Assurance Belgium (“MAB”) and Intégrale have reached an agreement under which MAB will acquire the entire portfolio and all the staff of the insurance company Intégrale. This agreement follows a firm offer from MAB, which was considered by the provisional administrators appointed by the National Bank of Belgium (“NBB”) to be that which best meets the interests of Intégrale policyholders and staff. The transaction remains subject to the final approval of the NBB. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210507005270/en/ During the transition period, MAB and Intégrale will take all steps necessary to prepare for a seamless transfer for policyholders, brokers and staff. In the meantime, Intégrale's staff will continue to service policyholders and brokers as usual. In addition to the transfer of assets at the time of closing, MAB will offer an 18-month employment guarantee to all employees and, in addition, a 3-mo

The Metals Company Joins European Industry Alliances to Bolster Battery Supply Chain for the Clean Energy Transition7.5.2021 11:00:00 EEST | Press release

Today, The Metals Company (formerly DeepGreen), a developer of the world’s largest and highest-grade estimated source of battery metals, announced it has joined two of the European Union’s foremost industrial alliances—the European Raw Materials Alliance (ERMA) and the European Battery Alliance (EBA)—as the bloc advances its plans to become a global leader in the sustainable production of the batteries necessary to store clean energy and power electric vehicles (EVs). As a member of these industrial alliances, The Metals Company—which announced in March its plans to go public via a merger with the Sustainable Opportunities Acquisition Corporation (NYSE: SOAC)—brings a new, scalable source of battery metals to the table in the form of polymetallic nodules found unattached on the deep seafloor in the Pacific Ocean, which can help deliver upon their mandate for a diverse, reliable and responsible supply of critical minerals needed for low-carbon technologies. Under its Green Deal, the Eur

Morocco and UN Celebrate First-Ever International Argan Tree Day7.5.2021 09:30:00 EEST | Press release

Morocco and the United Nations will be marking the first-ever International Argan Tree Day on May 10th, 2021. The Argan tree, a tree specific to the Kingdom of Morocco, will thus be celebrated every year on May 10, as an intangible cultural heritage of humanity and ancestral source of sustainable development. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210506005652/en/ February 22, 2021: The United Nations’ General Assembly adopted by consensus a resolution proclaiming May 10 of each year as the “International Argan Tree Day” (Photo: AETOSWire) The proclamation of the International Argan Tree Day was announced on March 3, 2021, when the UN General Assembly adopted by consensus a draft resolution initiated by Morocco and hailed by all United Nations’ member states. This milestone is a culmination of Morocco’s quest to mobilize the international community to protect and further develop the country’s Argan industry. It is al

Tigo Energy Demonstrates Optimization to Installers in Brazil with Stark Renováveis Installation7.5.2021 03:14:00 EEST | Press release

Tigo Energy, Inc., the solar industry’s leading Flex MLPE (Module Level Power Electronics) supplier, announced today that Stark Renováveis has used the Tigo TS4-A-O to mitigate energy lost due to shade on their corporate headquarters in São José do Rio Preto, Brazil. Their confidence in Tigo’s solution drove the selection of the products for their own use. The Tigo solution gives installers and commercial system owners the freedom to choose their preferred inverters and panels along with the right features for optimized, monitored and PV safe systems. The Stark Renováveis team chose a rooftop PV system with 405 Wp modules organized in multiple strings and using GoodWeTM grid-tied inverters. The optimum placement of the modules was on a roof bordering a large construction wall which would ordinarily lead to shade and a degradation of the output. To mitigate the problem of energy lost due to shade, Tigo TS4-A-O optimizers were deployed to ensure the best possible system performance. "As

93rd Vifor Pharma Group Annual General Meeting6.5.2021 19:00:00 EEST | Press release

Regulatory News: At today’s 93rd Annual General Meeting of Vifor Pharma Ltd., shareholders approved all proposed resolutions put forward by the Board of Directors. In view of the ongoing COVID-19 pandemic and in accordance with Ordinance 3 on measures to combat the coronavirus issued by the Swiss Federal Council, on the basis of Art. 8 of the new COVID-19 Act, shareholders were not permitted to attend the event in person. Shareholders exercised their rights exclusively through the independent proxy and 61.6% of the share capital was represented. Shareholder approvals Shareholders approved the Annual Report and the Annual Financial Statements of Vifor Pharma Ltd., as well as the consolidated Financial Statements of Vifor Pharma Group for 2020 by a large majority. The maximum possible 2022 remuneration for the Board of Directors and Executive Committee was also approved, as well as the 2020 Remuneration Report in a consultative vote. In addition, shareholders discharged the members of th

In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.

Visit our pressroom