ASCO24: Gilead seeks to revive Trodelvy lung cancer prospects with subgroup data

Gilead Sciences is striving to expand the use of Trodelvy (sacituzumab govitecan-hziy) into second-line treatment for lung cancer despite the drug failing to meet the primary endpoint in the Phase III EVOKE-01 trial. The antibody-drug conjugate (ADC), which targets Trop-2, is presently approved for breast and bladder cancers. The recent trial involved 603 patients with advanced or metastatic non-small-cell lung cancer (NSCLC) that had progressed following platinum-based chemotherapy and checkpoint inhibitors. In January, Gilead reported that Trodelvy did not significantly extend overall survival (OS) compared to the standard treatment, docetaxel, although there was a numerical improvement in OS.

The announcement led to an 11% drop in Gilead's shares, impacting the company's valuation by billions. This setback could provide an advantage to competitors, notably AstraZeneca and Daiichi Sankyo, which are advancing their own Trop-2 ADC, datopotamab deruxtecan (dato-DXd).

During an oral session at the American Society of Clinical Oncology (ASCO) conference, Gilead offered more insights into the EVOKE-01 results. Trodelvy reduced the risk of death by 16% compared to docetaxel, but this improvement lacked statistical significance. The median OS for Trodelvy was 11.1 months, compared to 9.8 months for docetaxel. Additionally, the drug showed no progression-free survival (PFS) benefit, with median PFS of 4.1 months versus 3.9 months for docetaxel. In contrast, dato-DXd has demonstrated a PFS advantage, particularly in non-squamous NSCLC, reducing the risk of disease progression or death by 37% compared to docetaxel, as per the Phase III TROPION-Lung01 trial results disclosed last October.

Interestingly, AstraZeneca and Daiichi Sankyo's TROPION-Lung01 study also did not show an OS benefit for dato-DXd compared to docetaxel. The FDA is currently reviewing a filing for dato-DXd, with a decision expected in the fourth quarter.

Despite the overall EVOKE-01 results falling short, Gilead emphasized a "meaningful OS improvement" among Trodelvy patients whose tumors did not respond to their last anti-PD-(L)1-containing treatment. This subset, which constitutes two-thirds of the study population, saw a median OS of 11.8 months, compared to 8.3 months for docetaxel, marking a 25% reduction in the risk of death. However, 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," stated lead author Luis Paz-Ares. On the other hand, patients who responded to their last anti-PD-(L)1-containing treatment had a higher risk of death with Trodelvy, showing a median OS of 9.6 months, compared to 10.6 months for docetaxel. For the overall study population, a numerically higher percentage of patients treated with Trodelvy were alive at 12 months compared to docetaxel, with survival rates of 46.6% and 36.7%, respectively.

In terms of safety, Trodelvy was better tolerated than docetaxel. Discontinuation rates due to treatment-related adverse events (TRAEs) were 6.8% for Trodelvy and 14.2% for docetaxel, while TRAEs leading to death occurred in 1.4% and 1.0% of patients, respectively.

In summary, while Trodelvy has shown encouraging results in certain subgroups, gaining approval based on a subset from a failed study remains challenging. Gilead remains optimistic about the potential benefits and is likely to pursue further investigations.

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