David M. Reese
Executive Vice President, Research and Development at Amgen
Thanks, Murdo. Good afternoon, everyone. For R&D, the second quarter was one of high quality execution as we progressed our innovative pipeline with two important data readouts, multiple registration enabling studies on track and additional exciting data coming later this year.
Beginning with oncology, we are exceptionally pleased to announce positive top line results from the global Phase 2 DeLLphi-301 trial evaluating tarlatamab, a first-in-class DLL3 targeting BiTE molecule in patients with relapsed or refractory small cell lung cancer that progressed after two or more prior lines of treatment.
Tarlatamab demonstrated an objective response rate at the primary endpoint that substantially exceeds what was previously reported in the Phase 1 study. Responses were durable and longer than what is expected with standard of care chemotherapy. Safety and tolerability were also more favorable compared to the Phase 1 study. This is the first time the device-specific T cell engager has shown unequivocal activity in a common solid tumor, a real milestone in the field.
We look forward to discussing these data soon with the FDA and other regulatory agencies and presenting detailed results of this potentially registrational Phase 2 study at an upcoming Medical Congress.
Based on the data we have observed, we are moving tarlatamab into earlier lines of therapy with DeLLphi-304, a Phase 3 study underway comparing tarlatamab with standard of care chemotherapy in second-line small cell lung cancer. We are also planning to initiate two additional Phase 3 studies of tarlatamab in earlier lines of small cell lung cancer.
From my personal vantage point as an oncologist, I believe this molecule can be transformative and can't wait to share these data with the field.
Turning to LUMAKRAS, we continue to execute on our comprehensive clinical program designed to generate the breadth of data necessary to understand KRAS biology and the role LUMAKRAS can play in non-small cell lung cancer, colorectal cancer, and other solid tumors.
We are delighted to announce that the global Phase 3 CodeBreaK 300 trial evaluating LUMAKRAS combined with Vectibix in chemo refractory metastatic KRAS G12C mutated colorectal cancer met its primary endpoint of progression-free survival for both the 240 milligram and 960 milligram doses. At comparable doses, efficacy results were consistent with what was previously observed in this setting with no new safety signals. We look forward to sharing these results with global health authorities and presenting the detailed results at an upcoming medical congress.
The FDA recently granted breakthrough therapy designation to LUMAKRAS in combination with Vectibix for the treatment of patients with metastatic KRAS G12C mutated colorectal cancer as determined by an FDA approved test who have received prior chemotherapy based on data from the prior CodeBreaK 101 study.
Beyond these data, we continue to explore novel combinations as we seek to move LUMAKRAS into the first-line setting. Recently presented data from the SCARLET study provide the rationale to initiate a Phase 3 trial of LUMAKRAS combined with chemotherapy in first-line non-small cell lung cancer patients with PD-L1 negative tumors and Phase 1b data in combination with Vectibix and chemotherapy support the initiation of a Phase 3 study of LUMAKRAS with Vectibix and FOLFIRI in first-line G12C mutated colorectal cancer.
In June, the FDA approved the supplemental biologics license application for BLINCYTO for the treatment of adults and pediatric patients with CD19-positive B-cell precursor acute lymphoblastic leukemia in first or second complete remission with minimal residual disease greater than or equal to 0.1%. The approval converts BLINCYTO's accelerated approval to a full approval.
Global regulatory submissions are on track for E1910, a Phase 3 trial conducted by the National Cancer Institute, Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network Cancer Research Group that demonstrated superior overall survival with BLINCYTO treatment added to consolidation chemotherapy over standard of care consolidation chemotherapy in newly diagnosed adult patients with Philadelphia negative ALL who were MRD negative following induction and intensification chemotherapy.
Three important updates were made to the National Comprehensive Cancer Network clinical practice guidelines in oncology in B-cell ALL. These included listing the BLINCYTO E1910 regimen as the only preferred regimen for the first line treatment of Philadelphia negative adult patients, adding BLINCYTO to multi-agent chemotherapy as consolidation in MRD negative disease, and lastly, moving BLINCYTO in combination with a tyrosine kinase inhibitor to the top of the treatment algorithm or MRD negative Philadelphia positive disease.
Finally, in April, data were published in the New England Journal of Medicine demonstrating that BLINCYTO added to chemotherapy improved two-year survival in KMT2A-rearranged B-ALL in infants compared to historical data. BLINCYTO two-year survival was 93% versus 66% for chemotherapy alone.
If you look at the totality of the data, it is clear that BLINCYTO is changing the paradigm for the treatment of B-cell ALL in late-stage disease, in early disease, in young patients and in older patients. We remain excited about its future potential and are focused on further investigating BLINCYTO in earlier lines of treatment and improving patient convenience through subcutaneous administration. As the first BiTE, BLINCYTO also provides a roadmap for the development of molecules such as tarlatamab, which could have enhanced activity in settings of lower tumor burden.
Two additional early oncology programs to watch are Xaluritamig and AMG 193. Xaluritamig is a first-in-class STEAP1 targeting bispecific being studied in advanced prostate cancer where STEAP1 is expressed on almost all tumor cells. We are observing significant anti-tumor activity with this molecule and are rapidly enrolling dose expansion cohorts. Xaluritamig provides another example of a bispecific T-cell engager demonstrating activity in a solid tumor setting.
AMG 193 is a first-in-class small molecule MTA-cooperative PRMT5 inhibitor being studied in patients with advanced MTAP-null solid tumors. The overexpression of PRMT5 in the absence of MTAP leads to the accumulation of MTA and we leverage this biology and the unique design of AMG 193, which requires the presence of MTA to effectively inhibit PRMT5.
Alterations in this pathway occur in approximately 15% of solid tumors, are often associated with a poor prognosis and historically have been very hard to drug. We are currently enrolling a Phase 1b/2 study of AMG 193. And while it is early, we are encouraged by the anti-tumor responses we've observed in multiple tumor types. We look forward to sharing data from both Xaluritamig and AMG 193 this fall.
In general medicine, we are advancing our cardiovascular franchise and emerging portfolio of obesity molecules with a focus on clinical trial execution. The Phase 3 outcomes study of olpasiran, our potentially best-in-class Lp(a) targeting small interfering RNA molecule and atherosclerotic cardiovascular disease, is enrolling well as is the Phase 2 study of maridebart cafraglutide, formerly known as AMG 133, in patients with obesity with or without diabetes and related comorbidities.
The goal of the Phase 2 study is to generate data that will provide broad optionality to design a Phase 3 program leveraging the unique properties of maridebart cafraglutide that will deliver strong sustainable weight loss.
In May, as mentioned, we presented data from a real world study of nearly half of a million post-menopausal women with osteoporosis in the United States Medicare program showing Prolia substantially reduced fracture risk in patients versus oral alendronate.
In addition, the same study showed that longer duration of Prolia treatment was associated with a greater reduction in major osteoporotic fracture risk. These data are a great demonstration of the importance of Prolia in treating post-menopausal osteoporosis and the ability to study treatment effects in large patient populations using real world evidence.
In inflammation, beyond severe asthma, we are investigating multiple additional indications with TEZSPIRE, including separate Phase 3 studies in chronic rhinosinusitis with nasal polyps and eosinophilic esophagitis.
We also have two Phase 2 studies, one in chronic spontaneous urticaria and the other in COPD. The CSU study is complete with top line data anticipated in imminently. The COPD trial is fully enrolled and has recruited a broad population of COPD patients, including patients with both high and low eosinophil counts. We look forward to the readout of this study in the first half of 2024.
On rocatinlimab, our first-in-class anti-OX40 monoclonal antibody being investigated in patients with moderate to severe atopic dermatitis, recruitment is off to a strong start on the ROCKET Phase 3 clinical development program. We are also planning to initiate a Phase 2 study in moderate to severe uncontrolled asthma as we explore rocatinlimab in this additional indication.
Rounding out the clinical summary, we've continued to execute both on time and on budget with our biosimilars portfolio, including the recent initiation of a pivotal study evaluating the pharmacokinetic similarity of ABP 206 compared with OPDIVO, one of six planned new biosimilars.
In closing, I'd like to highlight our recently announced collaboration with TScan Therapeutics. This is a multi-year collaboration that will use TScan's proprietary target discovery platform, TargetScan, to identify the antigens recognized by T-cells in patients with Crohn's disease and represents a novel approach to investigating this tough to treat illness.
I'd like to thank Amgen staff around the world for their relentless focus on execution as we work hard to meet the needs of the patients we serve.
I'll now turn it over to Peter.
