Irinotecan Hydrochloride Lioposome

Revolution Medicines (Nasdaq: RVMD) reported that its lead pipeline candidate, the RAS(ON) multi-selective inhibitor daraxonrasib, nearly doubled median overall survival (OS) versus chemotherapy in previously treated metastatic pancreatic ductal adenocarcinoma (PDAC), among the most pronounced survival separations recorded in a randomized pancreatic cancer trial. The RASolute 302 trial (NCT06625320) is a global, randomized, open-label Phase III study comparing daraxonrasib 300 mg orally once daily against investigator’s choice of cytotoxic chemotherapy in patients with previously treated metastatic PDAC, enrolling across a broad range of RAS variants. In the intent-to-treat population, daraxonrasib produced a median OS of 13.2 months versus 6.7 months for chemotherapy (HR 0.40, p<0.0001). The trial met both co-primary endpoints — progression-free survival (PFS) and OS in the RAS G12-mutant population — as well as all key secondary endpoints, including PFS and OS in the broader intent-to-treat population. The company stated that results from the first interim analysis are considered final. Numerical PFS data were not disclosed in the topline release. The safety summary was qualitative: daraxonrasib was described as generally well tolerated with no new safety signals identified. The 6.7-month control arm OS aligns with what has been observed historically in second-line PDAC chemotherapy, a setting where no targeted therapy has previously been approved for the dominant RAS-mutated population. More than 90% of PDAC patients harbor RAS mutations, predominantly G12D, G12V, and G12R, yet until now every approved targeted agent in this disease — olaparib for germline BRCA-mutated patients, pembrolizumab for the rare MSI-H subset, zenocutuzumab-zbco for NRG1-fusion tumors — collectively addresses fewer than 10% of patients. Daraxonrasib’s trial enrolled patients across that full RAS variant spectrum, including wild-type cases, making the breadth of the population studied a distinguishing feature of the program. Daraxonrasib is an oral, non-covalent RAS(ON) multi-selective inhibitor. It suppresses RAS signaling by blocking the interaction between the active, GTP-bound form of both wild-type and mutant RAS proteins and their downstream effectors. The approach differs from earlier allele-specific KRAS inhibitors, which target a single mutation such as G12C, and from indirect RAS pathway inhibitors such as MEK or RAF inhibitors. The non-covalent, multi-selective mechanism is designed to capture the range of G12 variants that collectively define the oncogenic landscape of PDAC, rather than restricting benefit to a single-allele subpopulation. The RAS inhibitor field has moved rapidly since the first approval of a direct KRAS inhibitor, sotorasib (Lumakras), for KRAS G12C-mutated non-small cell lung cancer in 2021, followed by adagrasib (Krazati). Both are covalent, allele-specific agents and have limited applicability in PDAC, where G12C is rare. Daraxonrasib’s design explicitly targets the more common G12D, G12V, and G12R variants that drive the overwhelming majority of pancreatic RAS-addicted tumors. Cross-trial comparisons are limited by differences in patient populations, prior therapy, and trial design, but the 0.40 hazard ratio reported in RASolute 302 is numerically distinct from what has been observed with cytotoxic regimens in this line of therapy. The oral once-daily dosing distinguishes daraxonrasib from the intravenous regimens that currently define second-line PDAC care — Onivyde plus 5-FU/leucovorin, gemcitabine plus nab-paclitaxel, and FOLFIRINOX variants — all of which require infusion infrastructure and clinic visits. That practical difference carries weight in a disease where performance status often deteriorates rapidly and quality of life was included as a secondary endpoint in RASolute 302. Revolution Medicines holds FDA Breakthrough Therapy Designation and Orphan Drug Designation for daraxonrasib in previously treated metastatic PDAC harboring G12 mutations, and the drug was selected for the FDA Commissioner’s National Priority Voucher pilot program. The company intends to submit a New Drug Application to the FDA under that voucher and to file with other global regulatory authorities. Data are also planned for presentation at the 2026 American Society of Clinical Oncology Annual Meeting, where full PFS figures, subgroup analyses, and detailed safety tables are expected to become available for independent evaluation. Beyond the second-line PDAC setting, Revolution Medicines has three additional Phase III registrational trials running in pancreatic cancer, including a first-line metastatic study evaluating daraxonrasib alone and in combination with gemcitabine plus nab-paclitaxel, and an adjuvant study in resected PDAC. A Phase III trial in RAS-mutated non-small cell lung cancer is also underway. The RASolute 302 readout is the first Phase III result from this program. The topline nature of the current disclosure means that several questions remain open before the full clinical picture can be assessed: the magnitude of PFS benefit, the consistency of OS results across RAS variant subgroups, the proportion of patients who crossed over at progression, and the granularity of adverse event rates by grade. Those details will determine how the data are interpreted by regulatory agencies and, if approved, how daraxonrasib is positioned relative to chemotherapy in clinical practice guidelines.

Ipsen telegraphed plans to acquire Epizyme and the FDA-approved Tazverik in June 2022, two years after the med’s clearance in the U.S. as both an epithelioid sarcoma and follicular lymphoma treatment. After an independent data monitoring committee raised safety flags in a clinical trial, Ipsen is shutting down the cancer med Tazverik, which it picked up through its acquisition of Epizyme less than four years ago.While the move may not have a major impact on Ipsen’s financial performance, it could shake confidence in the company’s business development acumen, at least one group of analysts contends. Specifically, the Paris-based drugmaker is voluntarily withdrawing Tazverik, also known as tazemetostat, across all indications and in all markets—including the U.S.—where it holds commercial rights to the EZH2 inhibitor, according to a March 9 press release.On the advice of a data monitoring committee that observed “adverse events of secondary hematologic malignancies” in the Tazverik study that prompted the withdrawal, Ipsen said it determined “the risk may outweigh potential benefits for patients within this treatment regimen.”The company said it has also started the process of stopping Tazverik treatment in patients enrolled in its phase 1b/3 Symphony-1 trial, where the blood cancer safety signals emerged. That study was looking at a combination of Ipsen’s drug with Revlimid plus Rituxan in relapsed or refractory follicular lymphoma. The drugmaker said it will continue long-term safety follow-up on all participants in the study and further nix “all active tazemetostat clinical trials and expanded access programs.”  Ipsen telegraphed plans to acquire Epizyme and the FDA-approved Tazverik in June 2022, two years after the med’s clearance in the U.S. as both an epithelioid sarcoma and a follicular lymphoma treatment. Monday’s market withdrawal announcement applies to both approved uses, Ipsen said. Ipsen’s partner in China, Hutchmed, has also begun to recall Tazverik in mainland China, Hong Kong and Macau and axe studies it was in charge of, according to a separate press announcement Monday. “While this is an extremely disappointing outcome, the safety of patients remains our priority,” Christelle Huguet, Ph.D., Ipsen’s R&D chief, said in a statement. “Emerging data from this confirmatory study have highlighted a safety profile that is unfavorable compared to that previously observed in clinical evaluation.”She continued: “We will now work closely with investigators and clinical teams to support patients through the respective next steps and transition plans.”Taking Tazverik out of its value equation would have a “minor impact” on Ipsen’s profile, analysts at Jefferies wrote in a note to clients Monday, citing “lackluster sales” of the drug to date. What’s more, Ipsen itself said in its 2025 earnings report last month that it no longer expects (PDF) Tazverik to hit the company’s 500 million-euro-plus peak sales target and that it has taken an impairment on the product.Ipsen logged a 13% decline in Tazverik sales last year, or 9.1% at constant exchange rates, with the drug bringing in 40.6 million euros (about $47 million) in 2025.The drug’s meandering sales and the “high risk” nature of Ipsen’s Symphony-1 trial have recently “put some scrutiny on management’s business development credibility,” the Jefferies team added in its note. Ipsen’s dealmaking strategy could become increasingly important in the coming years as the drugmaker runs up against expected patent cliffs for cancer medicines like Decapeptyl, Cabometyx and Onivyde, the analysts said.  Ipsen’s share price was down roughly 3% Monday morning ET. The company said it does not expect the Tazverik withdrawal to affect its financial forecast.The company recently reported total sales of 3.68 billion euros (around $4.3 billion) in 2025 and said it expects to chart sales growth greater than 13% in 2026.