Savolitinib

HUTCHMED announces new data from the sovleplenib ESLIM-01 Phase III trial and several investigator-initiated studies will be presented at the 2024 ASH Annual Meeting and ESMO Asia Congress. Long-term safety and efficacy data from the ESLIM-01 sub-study showed sovleplenib effectively increased and maintained platelet count in chronic primary ITP patients, with a well-tolerated safety profile.

Acquired resistance to osimertinib in EGFR-mutant NSCLC is common, with mechanisms including EGFR mutations, MET amplifications, and histologic transformation. Treatment options post-resistance include amivantamab, HER3-DXd, and Dato-DXd, with ongoing trials like ORCHARD aiming to optimize therapy based on resistance mechanisms.

Recent clinical studies in renal cell carcinoma (RCC) show immunotherapy-based combination regimens offer personalized treatment options, with confirmed benefits of entrenched regimens. Data from trials like CheckMate 214, CheckMate 9ER, and CLEAR support FDA approvals for combinations including nivolumab plus ipilimumab, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib. Long-term follow-up data reveal significant improvements in overall survival and progression-free survival, with biomarker analyses indicating consistent benefits across various RCC subgroups. The evolving landscape also includes second-line treatments like atezolizumab plus cabozantinib and adjuvant pembrolizumab, as well as HIF2α inhibitors like belzutifan. Research in non–clear cell RCC highlights the potential of immunotherapy combinations, with ongoing studies like PAPMET2 and KEYNOTE-B61 exploring new treatment strategies.

Osimertinib plus savolitinib showed a 90.5% objective response rate vs 60.9% for osimertinib alone in de novo MET-aberrant, EGFR-mutant advanced NSCLC, according to the phase II CTONG2008 (FLOWERS) trial. The combination demonstrated deeper and more durable responses, with a median duration of response of 18.6 months vs 8.4 months for monotherapy. However, the combination had more frequent grade 3 or higher adverse events.

Discussion on prognosis and treatment of non-clear cell renal cell carcinoma (nccRCC) vs clear cell RCC, highlighting worse outcomes for nccRCC, potential for immunotherapy response in sarcomatoid features, and ongoing trials like SAMETA and SUNNIFORECAST aiming to improve outcomes through molecular-driven therapy.

Combining osimertinib with savolitinib showed a 32% objective response rate in NSCLC patients with EGFR mutations and high MET overexpression/amplification after osimertinib failure, with a 49% response rate among those with high MET expression.

Osimertinib plus savolitinib combo shows high, durable ORR in EGFR-mutant, MET-overexpressed/amplified NSCLC patients progressing on osimertinib, per SAVANNAH trial. Safety profile consistent with known profiles; no new safety signals. Detailed results to be presented and submitted for regulatory review. FDA granted fast track designation in 2023.

HUTCHMED announced positive SAVANNAH Phase II trial results showing TAGRISSO plus ORPATHYS had a high, clinically meaningful ORR for EGFRm NSCLC patients with MET overexpression/amplification, whose disease progressed on TAGRISSO. The combination received Fast Track designation from the FDA in 2023. ORPATHYS, an oral MET TKI, is jointly developed by AstraZeneca and HUTCHMED, and approved in China for NSCLC with MET exon 14 skipping alterations. The safety profile of TAGRISSO plus ORPATHYS was consistent with known profiles. The global SAFFRON Phase III trial will further assess this combination versus platinum-based doublet chemotherapy.

Pharmaceutical companies are conducting clinical trials in Brazil and Turkey due to lower costs. Regulatory reforms by TITCK and ANVISA streamline approval processes, attracting major firms like AstraZeneca and Merck. Phase 3 trials for cancer drugs like Aflibercept and Savolitinib are underway. Collaboration with local institutions and CROs enhances trial quality and efficiency, positioning these countries as key clinical research hubs.

Lung cancer, a leading cause of cancer death globally, affects 2.4 million annually. TAGRISSO (osimertinib), a third-generation EGFR-TKI, is pivotal in treating EGFRm NSCLC, with extensive evidence supporting its use across various stages. AstraZeneca continues to innovate in lung cancer treatment, aiming to improve outcomes and redefine care.