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Chicago, here I come. The annual meeting of the American Society of Clinical Oncology kicks off tomorrow and runs through Tuesday, June 2.
Let’s set the table for cancer research’s big event, starting with the obvious headliner: Revolution Medicines and its RAS-blocking pancreatic cancer drug daraxonrasib. Full results from the company’s Phase 3 RASolute 302 study will feature prominently at ASCO’s plenary session on Sunday afternoon. The arena-sized exhibition hall will be jam-packed.
We already have the strongly positive topline results in hand from RevMed’s April press release: Patients with advanced pancreatic cancer who received daraxonrasib as a second-line treatment achieved a median overall survival of 13.2 months, compared to 6.7 months for patients offered standard chemotherapy.
Statistically, daraxonrasib reduced the risk of death by 60% compared with chemotherapy — an impressive result for a highly lethal cancer that had proved stubbornly resistant to targeted drugs and immunotherapy. Until now.
Daraxonrasib will almost certainly become the new standard of care for advanced pancreatic cancer upon approval, which also is likely to happen quickly, as soon as RevMed submits its application to regulators.
But details matter, so there’s still plenty to learn about the drug from the plenary presentation. The overall survival result disclosed in April came from an analysis of all patients enrolled in the study. On Sunday, we’ll get a breakdown of overall survival for subpopulations of patients, including those patients with tumors harboring RAS G12X mutations compared to patients with non-mutated tumors.
Duration of therapy in the study — assessed by progression-free survival — is important, especially from a commercial perspective. Investors are largely expecting daraxonrasib to show a median PFS in the range of seven to eight months, based on results from earlier studies.
The safety and tolerability of daraxonrasib, with special emphasis on frequency and severity of drug-related rash, also will be a key element of the plenary presentation.
Will Akeso’s ivonescimab data live up to this hype?
We’re just days away from finally seeing the overall survival results from Akeso’s Phase 3 HARMONi-6 study of ivonescimab in patients with newly diagnosed squamous, non-small cell lung cancer. The study is also being featured in Sunday’s plenary session.
Ivonescimab, for those who need reminding, is the closely tracked PD-1/VEGF-targeted immunotherapy that Akeso invented in China, and then licensed globally to Summit Therapeutics. The buzz (some might say hype) around this class of drugs — Big Pharma pipelines are full of them — is that they may one day supplant Keytruda as the cancer immunotherapy standard bearer.
I have already written about the curious internet flyers that used terms such as “redefining survival,” “setting a new survival standard,” and “history making” to promote the outcome of the HARMONI-6 study, which was also conducted entirely in China. Akeso produced the flyers for its Chinese audience and confirmed their authenticity to a Cantor biotech analyst, but the company has not responded to my inquiries.
Words matter. Numbers matter more. For HARMONi-6, investor expectations have settled on an overall survival hazard ratio in the range of 0.70 to 0.80 — or a 20%-30% reduction in the risk of death favoring ivonescimab over tislelizumab, the PD-1 checkpoint inhibitor from BeOne Medicines used in the control arm. (Patients in both arms also receive chemotherapy.)
Helpful tip: A lower hazard ratio is better, so a result closer to 0.70 or even lower should be viewed positively.
The improvement in median overall survival, measured in months, will also matter.
Based on their own expert calls, Cantor analysts believe a six-month or greater improvement in median overall survival will be viewed as clinically meaningful.
In a preview note, Jefferies analysts peg a “base case” outcome for median overall survival at 25 months for the ivonescimab arm versus 19 months for the tislelizumab arm — a difference (benefit) of six months.
Here’s another lung cancer data point to keep in mind: In its own Phase 3 clinical trial called RATIONALE-307, also conducted entirely in China, tislelizumab plus chemo showed a median overall survival of 22.8 months.
The HARMONi-6 study enrolled patients with more severe disease, so there’s an expectation that the tislelizumab plus chemo arm will underperform the RATIONALE-307 benchmark, boosting ivonescimab’s benefit.
We’ll see soon enough.
More ASCO presentations of note
On Friday, Bristol Myers Squibb will report results from the Phase 3 SUCCESSOR-2 study of mezigdomide in second-line multiple myeloma. Mezigdomide is part of a Bristol research effort to develop a new and more potent class of blood cancer drugs called CELMoDs to replace its older medicines Pomalyst and Revlimid in standard-of-care treatment regimens for multiple myeloma.
The mezigdomide data presented at ASCO will have read-through implications for C4 Therapeutics, a biotech developing a potentially competing drug called cemsidomide.
On Saturday, Cogent Biosciences will present full results from the Phase 3 PEAK study that evaluated its drug bezuclastinib in advanced gastrointestinal stromal tumors, or GIST. Top-line, positive results from the study were announced last November. The drug has already been submitted to the FDA for potential approval.
I mentioned the crowded race to develop PD-1/VEGF inhibitors. Pumitamig, from BioNTech and Bristol Myers Squibb, is one of them. On Saturday, results from the Phase 2 portion of the ROSETTA Lung-02 study in first-line non-small cell lung cancer will be presented.
On Tuesday, Celcuity will report results from the Phase 3 VIKTORIA-1 study evaluating gedatolisib in patients with advanced HR-positive, HER2-negative breast cancer that also carries a PIK3CA mutation. Last October, Celcuity presented positive results from the same study but in a cohort of patients with breast cancer without the PIK3CA mutation.
STAT @ ASCO housekeeping notes
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If you’ll be in Chicago for the meeting, come hang out with STAT at our live event on Friday evening. I will be interviewing Revolution Medicines CEO Mark Goldsmith. We’ll have A LOT to discuss.
Former FDA official Rick Pazdur will also be making an onstage appearance.
More details about our event and registration can be found here.
Muir Beach, Calif.
Thanks for reading! Until next week,
