SAFFRON met both of its main goals in lung cancer and was published in a major medical journal. CLARITY-Gastric01 cut the risk of death by 42%, but reports from the congress said its progression-free survival endpoint was missed. AstraZeneca reports third-quarter results on Friday.
AstraZeneca goes into its third-quarter report on Friday with more new clinical data to explain than any quarter's numbers will show.
Over the weekend, the company presented two Phase 3 trials of its own at the European Society for Medical Oncology congress and watched its immunotherapy Imfinzi lose a survival comparison in a third, run by a rival. A day earlier, Amgen's Imdelltra, given with Imfinzi, cut the risk of death by 58% in a separate trial.
The clean win
SAFFRON tested AstraZeneca's Tagrisso combined with savolitinib in patients with mutated non-small cell lung cancer. The combination extended median progression-free survival to 7.6 months from 5.4, a hazard ratio of 0.55. Median overall survival rose to 17.8 months from 12.9, a hazard ratio of 0.68. The survival result cleared the trial's significance threshold, with 53% of the expected deaths recorded.
Both main goals were met. The results were published simultaneously in the New England Journal of Medicine on Sunday evening, according to HUTCHMED, which on Monday also presented its SANOVO Phase 3 trial combining its drug Orpathys with Tagrisso in previously untreated EGFR-mutated lung cancer. For an established drug like Tagrisso, positive combination trials are a way to extend its use.
The split verdict
CLARITY-Gastric01 is harder to read. AstraZeneca's release led with survival: its antibody-drug conjugate sonesitatug vedotin reduced the risk of death by 42% in previously treated, CLDN18.2-positive advanced gastric cancer, with median overall survival of 10.6 months against 6.4. In patients in the third line of treatment or later, the hazard ratio was 0.47 and median survival doubled, to 10.0 months from 5.0. Twelve-month survival was 38.1% against 18.1%.
The trial had two primary endpoints, survival in later-line patients and progression-free survival. AstraZeneca's announcement focused on survival. Fierce Biotech reported from the congress that the progression-free endpoint was missed, with a median of 4.2 months for the drug, and quoted a company executive describing the data as robust enough to support approval.
That leaves a framing question the company will likely be asked on Friday: whether a strong survival benefit outweighs a missed co-primary endpoint in regulators' eyes.
The comparator that lost
In Akeso's HARMONi-GI1 trial, run only in China, ivonescimab plus chemotherapy beat Imfinzi plus chemotherapy on survival in biliary tract cancer, with a hazard ratio of 0.75. AstraZeneca bought a stake equivalent to about 12% of Summit Therapeutics, ivonescimab's partner outside China, four weeks ago, and is planning combination trials with its own drugs. A loss for one of its products is also data on a molecule in which it now has a financial interest.
Two readings
The constructive reading is that the weekend broadened AstraZeneca's oncology pipeline: a clean Tagrisso combination now in a peer-reviewed journal, a new drug with a large survival benefit in a hard-to-treat cancer, and a partner drug, Imdelltra, that showed Imfinzi working in combination.
The cautious reading is that the CLARITY progression-free miss creates regulatory uncertainty for one of its newer assets, and that a randomized loss for Imfinzi in a new indication marks the competitive pressure building on its immunotherapy franchise.
AstraZeneca's U.S.-listed shares closed Friday at $171.49, before any of the data. Monday is the stock's first chance to respond.
What to watch
Monday's trading, the full CLARITY-Gastric01 presentation and any company statement on the progression-free result, and AstraZeneca's third-quarter results and call on Oct. 30, where management will be asked about regulatory plans for both trials.