Lenvatinib mesylate

AstraZeneca said a treatment regimen anchored by its PD-L1 inhibitor Imfinzi (durvalumab) and anti-CTLA-4 antibody Imjudo (tremelimumab) succeeded in the Phase III EMERALD-3 trial in patients with hepatocellular carcinoma (HCC).The study is seen as an important test of whether using every available treatment strategy right from the start can improve outcomes for liver cancer patients, though some key opinion leaders (KOLs) worry such an aggressive approach may be too harsh for routine practice and could leave patients with fewer treatment options later on.EMERALD-3 includes 760 patients with unresectable, locoregional HCC who are eligible for embolisation. Participants received either the STRIDE regimen – consisting of single-dose Imjudo plus regular-interval Infinzi – with transarterial chemoembolisation (TACE); the same immunotherapy backbone plus Eisai's VEGF receptor inhibitor Lenvima (lenvatinib) and TACE; or TACE alone.Eye on OSAstraZeneca said the quadruplet approach achieved significant and clinically meaningful improvement on the primary endpoint of progression-free survival (PFS), compared to TACE alone. Overall survival (OS), a key secondary endpoint, showed a trend in favour of this combination as well, but data are still immature.Although it hasn't yet been formally tested, AstraZeneca said early data from the treatment arm that didn't receive Lenvima revealed "strong trends" toward improved PFS and OS.The trial will continue to follow OS in both investigational arms, though the company is optimistic. Susan Galbraith, head of oncology haematology R&D at AstraZeneca, said EMERALD‑3 builds on the Phase III HIMALAYA results, "where the STRIDE regimen has already demonstrated durable overall survival benefit."HIMALAYA tested the combination of Imfinzi and Imjudo in HCC patients with advanced, unresectable disease. Long-term data presented at the European Society for Medical Oncology (ESMO) conference in 2024 showed that nearly 20% of patients given the combination were alive at five years, roughly double the OS rate with Bayer's Bayer's Nexavar (sorafenib).However, earlier efforts to combine Imfinzi with TACE got a mixed reception in the Phase III EMERALD‑1 study a few years ago, where PFS benefit depended on the inclusion of Roche's Avastin (bevacizumab).Toxicity concernsMeanwhile, AstraZeneca said the safety profile for each combination in EMERALD-3 was consistent with the known profiles of each medicine, adding there were no new safety findings. More details will be shared at a forthcoming medical meeting and shared with global regulatory authorities.KOLs interviewed for a FirstWord report voiced serious concerns about toxicity especially given the aggressive use of agents targeting PD-L1, CTLA-4 and VEGF pathways in a patient population that often has cirrhosis or compromised liver function."It will be interesting to see how patients tolerate this," said one US-based KOL. "I think one of the issues with EMERALD-1 that we saw was that there were a lot of dropouts…I just wonder about the kind of additional toxicities that we might see when we keep adding therapies. That being said, you might get a prolonged response in some of these patients."

IMFINZI plus IMJUDO combined with lenvatinib and TACE demonstrated a statistically significant and clinically meaningful improvement in progression-free survival in embolization-eligible unresectable liver cancer in EMERALD-3 Phase III trial IMFINZI plus IMJUDO combined with lenvatinib and transarterial chemoembolization (TACE) showed trend toward improved overall survival WILMINGTON, Del.--(BUSINESS WIRE)--Positive high-level results from the EMERALD-3 Phase III trial showed AstraZeneca’s IMFINZI ® (durvalumab) in combination with IMJUDO ® (tremelimumab-actl), lenvatinib and transarterial chemoembolization (TACE) demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) versus TACE alone for patients with unresectable hepatocellular carcinoma (HCC) eligible for embolization. At this interim analysis for overall survival (OS), a key secondary endpoint, this combination also demonstrated a trend toward OS improvement versus TACE alone. Patients in the investigational arms were treated with the STRIDE regimen (Single Tremelimumab-actl Regular Interval Durvalumab), with or without lenvatinib, before TACE, and then alongside TACE. Although not formally tested at this time, data for the treatment arm evaluating the STRIDE regimen plus TACE versus TACE alone showed strong trends toward improved PFS and OS. The trial will continue to follow OS and other key secondary endpoints in both investigational arms. HCC is the most common type of liver cancer. 1 In 2026, more than 200,000 patients with HCC will be eligible for embolization, a standard-of-care procedure that blocks the blood supply to the tumor and can also deliver chemotherapy directly to the liver. 2-4 However, most patients who receive embolization experience disease progression or recurrence within six to 10 months. 5 Ghassan Abou-Alfa, MD, JD, MBA, PhD(hc), Attending Physician, Professor of Medicine at Memorial Sloan Kettering Cancer Center, and principal investigator in the trial, said: “Dual immunotherapy with durvalumab and tremelimumab-actl in the STRIDE regimen represents a meaningful advance for patients with embolization-eligible liver cancer, who currently lack systemic treatment options to keep their cancer from progressing or recurring, with a trend of improving survival. EMERALD‑3 shows we can now significantly reduce the risk of disease progression with STRIDE as the immunotherapy backbone alongside lenvatinib and TACE.” Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “EMERALD‑3 now shows that bringing the dual immunotherapy STRIDE regimen earlier, alongside TACE and lenvatinib, can further improve outcomes in earlier‑stage liver cancer. This builds on the HIMALAYA Phase III trial data in patients with advanced, unresectable disease, where the STRIDE regimen has already demonstrated durable overall survival benefit. We are discussing these positive data with global regulatory authorities while awaiting the final results from the key secondary endpoints.” The safety pro each combination was consistent with the known profiles of each medicine, and there were no new safety findings. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. IMPORTANT SAFETY INFORMATION There are no contraindications for IMFINZI ® (durvalumab) or IMJUDO ® (tremelimumab-actl). Severe and Fatal Immune-Mediated Adverse Reactions Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. 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. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg 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. Immune-Mediated Pneumonitis IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. IMFINZI as a Single Agent In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and COVID-19 (1.1%). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm. Metastatic NSCLC In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in ≥20% of patients) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%). In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in 17% of patients. Serious adverse reactions occurred in 44% of patients, with the most frequent serious adverse reactions reported in at least 2% of patients being pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients. Limited-stage Small Cell Lung Cancer In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), the most common adverse reactions occurring in ≥20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38%), and fatigue (21%). Contacts Media Inquiries Lauren-Jei McCarthy +1 347 918 7001 US Media Mailbox: usmediateam@astrazeneca.com Read full story here