ASCO24: Gilead looks to redeem Trodelvy lung cancer hopes with subgroup data

31 May 2024
Clinical ResultPhase 3ASCOADC
Despite missing the primary endpoint in the Phase III EVOKE-01 trial, Gilead Sciences highlighted some positive subgroup data on Friday in a bid to salvage its quest to broaden Trodelvy's (sacituzumab govitecan-hziy) label into second-line lung cancer. However, persuading US regulators to grant approval based on a subset of patients from a failed study could be an uphill battle.
The Trop-2-directed antibody-drug conjugate (ADC) is already approved for breast and bladder cancers. In January, the company reported top-line results showing that despite a numerical improvement on the main overall survival (OS) endpoint, Trodelvy did not significantly prolong OS compared to standard treatment with docetaxel in the 603-patient study. Participants in the trial had advanced or metastatic non-small-cell lung cancer (NSCLC) that progressed after platinum-based chemotherapy and checkpoint inhibitors.
Investors reacted with an 11% drop in the company's shares, shaving billions off its valuation at the time. The setback may have also given momentum to AstraZeneca and Daiichi Sankyo's competing Trop-2 ADC datopotamab deruxtecan (dato-DXd).
No PFS benefit
In a Friday oral session at the annual American Society of Clinical Oncology (ASCO) conference, Gilead gave more details about the EVOKE-01 results, saying its drug led to a 16% reduction in the risk of death compared to docetaxel. Despite a numerical improvement seen across both squamous and non-squamous histology, that difference missed the bar of statistical significance. Median OS was 11.1 months for patients who took Trodelvy, versus 9.8 months for the comparator arm.
On the secondary endpoint of progression-free survival (PFS), Trodelvy-treated patients fared not much better than docetaxel, with median PFS of 4.1 months and 3.9 months, respectively. By contrast, dato-DXd has shown a PFS benefit, specifically in patients with non-squamous disease, where the risk of disease progression or death was 37% lower compared to docetaxel, according to results from the Phase III TROPION-Lung01 study unveiled last October.
Earlier this week, AstraZeneca and Daiichi Sankyo shared the final analysis from TROPION-Lung01, which had also failed to show an OS benefit compared to docetaxel. An FDA filing is currently under review for dato-DXd, with a decision expected in the fourth quarter.
'Meaningful' OS in immunotherapy non-responders
While the overall OS results for EVOKE-01 fell short, Gilead did highlight a "meaningful OS improvement" of 3.5 months among Trodevly patients whose tumours did not respond to their last anti-PD-(L)1-containing treatment, translating to a 25% reduction in the risk of death. This subset, which accounts for two-thirds of the study population, achieved a median OS of 11.8 months, compared to 8.3 months for docetaxel, although the company noted that the analysis wasn't powered for formal statistical testing.
"These data, including the meaningful benefit observed in the subgroup of patients, are encouraging and warrants further investigation as these patients have a great unmet need," commented lead author Luis Paz-Ares.
On the flip side, patients who did respond to their last anti-PD-(L)1-containing treatment showed a higher risk of death. Those in the Trodelvy arm had a median OS of 9.6 months, whereas those on docetaxel were alive a month longer. Gilead noted that for the overall study population, a numerically higher percentage of patients were alive at 12 months when treated with Trodelvy compared to docetaxel, with survival rates of 46.6% and 36.7%, respectively.
Safety-wise, Gilead's drug was better tolerated in the study. Among patients receiving Trodelvy and docetaxel, 6.8% and 14.2% discontinued because of treatment-related adverse events (TRAEs), respectively, while 1.4% and 1.0% had TRAEs leading to death.
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