Dean Y. Li
Executive Vice President and President-Merck Research Laboratories, at Merck & Co., Inc.
Thank you, Caroline. Good morning, everyone. Today, I will start with our oncology programs, followed by vaccines, immunology and conclude with cardiometabolic disease. Over the last few years, our oncology strategy has focused on leveraging the remarkable properties of KEYTRUDA to establish a diverse clinical pipeline of candidates with novel mechanisms and modalities. This is broadly based on 3 strategic pillars: immuno-oncology, precision oncology and tissue targeting.
In immuno-oncology, we continue to evaluate KEYTRUDA in the metastatic and increasingly in earlier-stage disease settings while also investigating multiple novel immuno-oncology combinations and co-formulations. With precision oncology, we are selectively targeting pathways to inhibit cancer cell growth. And in tissue targeting, we are developing agents such as antibody drug conjugates designed to increase cancer cell sensitivity and killing. The latter is exemplified by our recently announced collaboration with Daiichi Sankyo. Daiichi Sankyo scientists have made pioneering contributions in advancing novel antibody drug conjugate technology with proven benefit to patients.
By combining our companies' respective strength, we are well positioned to accelerate 3 clinical stage potentially first-in-class candidates with the goal of transforming the treatment paradigm. These include patritumab, deruxtecan, an investigation of fully humanized anti-HER3 ADC in Phase III; infinitumab, deruxtecan, an investigation of humanized anti-B7-H3 ADC in Phase II; and Rally tag deruxtecan, an investigation or humanized anti-CDH6-targeted ADC in Phase I. We provided details during our investor event earlier this week, and are eager to begin working with the team.
The Daiichi Sankyo collaboration complements our important ongoing alliance with Kelun Biotech, whose talented scientists have developed their own innovative ADC platform. At ESMO new Phase II data for MK-2870 or SKB 264, a TROP2 targeting ADC in patients with previously treated metastatic hormone receptor positive HER2-negative breast cancer, showed encouraging antitumor activity with an objective response rate of 36.8%. This builds on existing data for MK-2870, both in triple-negative breast and non-small cell lung cancer.
We are now poised to initiate larger studies, starting with non-small cell lung cancer and expand into additional tumor types. We are also advancing clinical development of MK-1200 and ADC targeting cloud and 18.2. Recognizing the proven benefit of KEYTRUDA in combination with chemotherapy in certain tumor types, we are exploring the tissue targeting concept by evaluating regimens combining ADCs and immunotherapy. At ESMO, in collaboration with CGN and Astellas, potentially practice-changing survival data were presented from KEYNOTE-A39, EV-302, evaluating KEYTRUDA plus enfortumab vedotin as first-line treatment for patients with locally advanced or metastatic urothelial carcinoma.
This regimen represents the first approval of a combination of a checkpoint inhibitor and an ADC. Turning to immuno-oncology. Evidence continues to emerge for the benefit of KEYTRUDA in the treatment of earlier stage cancer. Positive survival data from KEYNOTE-671, evaluating KEYTRUDA in combination with platinum doublet chemotherapy as neoadjuvant therapy, followed by adjuvant KEYTRUDA in patients with resectable Stage 2, 3a or 3b non-small cell lung cancer compared to preoperative chemotherapy, were presented at ESMO, further reinforcing the benefit of routine lung cancer screening for certain populations to enable early intervention.
Based on the KEYNOTE-671 results, last week, the FDA approved this indication with a differentiated label that includes overall survival. KEYTRUDA has now been approved for 6 indications to treat patients with non-small cell lung cancer. KEYNOTE-671 represents the ACE approval for KEYTRUDA in earlier stage cancer. Positive data from additional early-stage studies in women's cancer were also presented at ESMO: for KEYNOTE-756 in patients with estrogen receptor positive HER2-negative breast cancer; for KEYNOTE-522 and high-risk early-stage triple-negative breast cancer; and KEYNOTE A-18 for patients with high-risk locally advanced cervical cancer.
Now the FDA recently granted priority review for KEYTRUDA based upon this study, with a target action date of January 20. We also announced KEYTRUDA significantly improved disease-free survival for the adjuvant treatment of patients with localized muscle invasive and locally advanced urothelial carcinoma based on KEYNOTE-123. And finally, in collaboration with Moderna, the Phase III trial for KEYTRUDA in combination with V940 in individualized neoantigen therapy in earlier-stage non-small cell lung cancer has now been posted and is poised to start soon.
In Precision Oncology, our efforts continue to yield progress. WELIREG, our HIF-2 alpha inhibitor, is approved for treatment of certain cancers and patients with vonhipo/lindal disease, a rare cancer-prone genetic disorder. Studies evaluating WELIREG in broader populations of patients whose tumors display analogous genetic underpinnings are ongoing. Data presented at ESMO from Light Spark 005 evaluating WELIREG for adult patients with advanced renal cell carcinoma, following immune checkpoint and anti-angiogenic therapies, showed statistically significant and clinically meaningful improvement in progression-free survival versus the standard of care.
These findings support our supplemental new drug application for WELIREG, which was granted priority review by the FDA with a target action date of January 17. Additional Phase III studies in combination with KEYTRUDA and onlivacanib in advanced and adjuvant renal cell carcinoma are proceeding. First-time safety and preliminary efficacy data for MK-1084, our oral KRAS inhibitor, both as monotherapy in patients with solid tumors and in combination with KEYTRUDA for metastatic non-small cell lung cancer whose tumors harbor KRAS G12C mutations, were presented at ESMO. Notably, the combination arm showed a compelling objective response rate of 71%. While the data are early, we are encouraged by the potential to combine MK-1084 with KEYTRUDA.
In the hematologic space, we will begin enrolling patients in our Phase III study evaluating MK-3543/orbomadenstat, a second-line treatment for essential thrombocythemia, an area with tremendous patient need. Bomedenstet is derived from our acquisition of Imago. Outside of the U.S., the European Union granted approval for KEYTRUDA for adjuvant treatment of patients with non-small cell lung cancer who are at high risk of recurrence, following complete resection and platinum-based chemotherapy based on KEYNOTE-091.
And for KEYTRUDA, in combination with trastuzumab and chemotherapy, as first-line treatment for patients with certain gastric or gastroesophageal junction adenocarcinoma based on KEYNOTE-811. In Japan, Lynparza, in combination with aboretinol and prednisone, was approved for BRCA-mutated metastatic castration-resistant prostate cancer with distant metastasis based on the PROPEL study. Now to our broader pipeline. Building on the ongoing launch of VAXNEUVANCE, which Caroline mentioned, progress continues in our population-focused pneumococcal conjugate vaccine program.
V116, our investigational pneumococcal conjugate vaccine specifically designed for adults, has demonstrated a robust immune response to all 21 serotypes in the STRIDE-003 and STRIDE-006 studies. Detailed findings from the STRIDE-003 study will be presented at the World Vaccine Congress West Coast in November. If approved, V116 would be the first pneumococcal conjugate vaccine specifically designed to address serotypes responsible for the majority of adult invasive pneumococcal disease in adults. Our company has deep expertise, given our breadth and depth of knowledge both in immuno-oncology and vaccines. We are leveraging these capabilities in immunology where the first patient is ready to be enrolled in the Phase III trial for MK-7240 in ulcerative colitis.
Turning to cardiometabolic disease programs. Last month at the European Respiratory Society International Congress, we presented data for setatersen, currently under review by the FDA for the treatment of adults with pulmonary arterial hypertension. In an exploratory post-hoc analysis of right heart authorization and echocardiography data from patients in the Phase III STELLAR study, patients with PAH treated with Sotatercept for 24 weeks on top of background therapy showed a reduction in right heart size and improved right ventricular function and hemodynamic status. In addition, we presented promising data from an analysis of the Phase III Tutera open-label extension study in PAH.
The results support the potential long-term durability of the response to Sotatercept and represent the longest safety and efficacy analysis for this compound to date. Given the serious patient need in pulmonary arterial hypertension, our regulatory and clinical teams work swiftly to submit the necessary regulatory filings for Sotatercept. The FDA has accepted the biologics license application under priority review, with a target action date of March 26. In addition, the submission to the Committee for Medicinal Products for human use in the European Union has been completed. Also in cardiology, momentum continues in the clinical development program for MK-0616, our RLPCSK9 inhibitor.
We have initiated the Coral Reef lipid study in a broad patient population and coral reef outcomes, a randomized double-blind study evaluating the efficacy of MK-0616, with respect to major atherosclerotic cardiovascular events as well as a separate coral reef study in patients with heterozygous familial hypercholesterolemia. Over the last three years, we have moved with rigor and urgency to advance the best science while carefully coordinating our efforts internally and externally.
We have and continue to leverage the foundational properties of KEYTRUDA while adding promising candidates with novel mechanisms and modalities in oncology. At the same time, we have expanded in our focused areas of excellence to establish a diverse pipeline of promising candidates spanning multiple additional disease areas. We understand there is still work to be done, but the tangible advances we are making underscore our purpose of creating innovative medicines and vaccines that save and improve lives. And now I turn the call back to Peter.
