Gilead’s $21bn cancer gamble faces major blow as Trodelvy fails in key breast cancer trial

Gilead Sciences Inc. (NASDAQ: GILD) encountered a setback in its oncology ambitions with the announcement that Trodelvy, its lead antibody-drug conjugate asset, failed to meet the primary efficacy endpoint in a Phase 3 study targeting a broad first-line breast cancer population. The study, ASCENT-07, enrolled 654 patients with hormone receptor-positive, HER2-negative (HR+/HER2–) metastatic breast cancer who had progressed on endocrine therapy. Trodelvy was being tested against physician’s choice chemotherapy, with progression-free survival as the trial’s main objective.

The company disclosed that while an early trend in overall survival emerged in favor of Trodelvy, it did not reach statistical significance for progression-free survival. The stock market responded with a 2% intraday decline in Gilead Sciences Inc. shares, as institutional investors recalibrated expectations for near-term oncology revenues.

Trodelvy, also known by its generic name sacituzumab govitecan-hziy, is already approved for later-line metastatic triple-negative breast cancer and heavily pre-treated HR+/HER2– breast cancer. The failure to extend this use into the frontline setting in a larger population deals a blow to Gilead Sciences Inc.’s goal of expanding the drug’s commercial footprint, which had been a central pillar of its $21 billion acquisition of Immunomedics in 2020.

Why did Gilead Sciences’ trial fall short, and what made this indication more difficult to crack?

Trodelvy’s struggle in the first-line HR+/HER2– metastatic setting reflects the complex treatment dynamics of this breast cancer subtype. This category accounts for roughly 70% of all breast cancer cases globally, making it a key battleground for biopharmaceutical companies seeking high-volume, front-line approvals. However, the heterogeneity of the disease, especially in patients who have already failed endocrine therapy, presents a clinical challenge.

In the ASCENT-07 study, Trodelvy was administered to patients who had exhausted hormonal options but not yet received chemotherapy. The expectation was that its antibody-drug conjugate mechanism would deliver a significant benefit over traditional chemotherapies. However, trial investigators noted that the disease’s diverse biology made it difficult to achieve a meaningful progression-free survival edge, particularly when competing against well-understood cytotoxic agents that physicians are comfortable prescribing.

Notably, the safety profile of Trodelvy remained consistent with earlier studies, and no new adverse signals were reported. But for a therapy to be successful in the first-line setting, the efficacy bar is significantly higher than in salvage or third-line populations. The inability to deliver a superior PFS outcome in this population likely dims the drug’s potential to challenge incumbent therapies or earn a broader label.

What does this mean for Gilead Sciences Inc.’s growth strategy in oncology?

The failure of ASCENT-07 represents more than just a data disappointment—it impacts Gilead Sciences Inc.’s narrative around diversifying beyond its core HIV and hepatitis franchises. Since acquiring Immunomedics, the company has invested heavily in oncology pipeline development, positioning Trodelvy as a foundational asset.

This outcome follows other recent oncology challenges for the company, including the October 2024 decision to voluntarily withdraw the bladder cancer indication for Trodelvy due to underwhelming efficacy in post-approval studies. Combined, these developments raise concerns about how Gilead Sciences Inc. is selecting and de-risking its late-stage trials, especially in large, competitive markets.

Nevertheless, executives at Gilead Sciences Inc. remain committed to the oncology space. The company is pursuing multiple Trodelvy studies in earlier-stage breast cancers, as well as gynecologic, lung, and bladder cancers, including combinations with checkpoint inhibitors such as Merck’s Keytruda. In April 2025, a separate study showed that a Trodelvy–Keytruda combo produced encouraging results in more aggressive breast cancer subtypes, suggesting future growth avenues may depend on synergistic regimens rather than standalone applications.

How are investors and institutions reacting to this latest clinical setback?

Market reaction to the ASCENT-07 outcome was measured but directionally negative. Shares of Gilead Sciences Inc. dipped modestly following the announcement, indicating that the trial risk had already been partially priced into the stock. Still, analysts who had modeled upside from first-line Trodelvy use may now revise their oncology revenue forecasts downward.

Early commentary from the buy-side suggests that long-term investors remain supportive of the company’s stable cash flows from HIV and liver therapies, which continue to generate reliable returns. However, hedge fund activity appears to be leaning cautious, with some capital rotation toward competitors with more validated oncology pipelines. Gilead Sciences Inc.’s dividend stability and balance sheet strength provide insulation, but the pressure is now higher for its oncology unit to deliver near-term wins or potential business development surprises.

From an investor relations standpoint, Gilead Sciences Inc. will need to carefully manage messaging in the next earnings cycle, particularly as analysts scrutinize whether oncology remains a viable driver of long-term valuation uplift or whether it should be treated as an opportunistic rather than strategic segment.

What are the broader implications for antibody-drug conjugates and competitive positioning?

Trodelvy’s failure in this setting has implications that extend beyond Gilead Sciences Inc. to the broader antibody-drug conjugate (ADC) field. While ADCs have generated considerable enthusiasm due to their targeted delivery mechanisms, translating that advantage into first-line survival benefits has proven difficult. The class includes powerful drugs like Enhertu, jointly developed by AstraZeneca and Daiichi Sankyo, which has shown promise in HER2-positive and HER2-low populations.

This setback may temper some of the hype around ADCs as front-line solutions and reinforce the need for biomarker-based stratification or combination therapies. For developers in the HR+/HER2– space, the door remains open—but the bar is now higher. Trodelvy may still find use in narrower patient subgroups or tumor profiles, particularly if biomarker or genomic analyses from ASCENT-07 reveal subsets that respond meaningfully.

What should stakeholders expect next from Gilead Sciences Inc. and Trodelvy’s future?

The immediate priority for Gilead Sciences Inc. will be to complete and disclose the overall survival data from the ASCENT-07 trial. Even if the progression-free survival benchmark was missed, an overall survival advantage in any subset could offer a regulatory lifeline or support label expansion in selected populations.

Beyond that, the company will likely focus on combination studies and expanding the Trodelvy franchise through immunotherapy pairings, as well as investing in alternative oncology assets or partnerships. With its strong balance sheet and proven capabilities in scaling drugs in other therapeutic areas, Gilead Sciences Inc. is unlikely to retreat from oncology altogether—but the spotlight now shifts to how it adapts its clinical strategy and communicates with institutional investors seeking predictable growth catalysts.

For now, analysts will be watching closely to see whether the Trodelvy–Keytruda combination, ongoing gynecological cancer trials, or upcoming regulatory filings can shift sentiment and reignite optimism in Gilead Sciences Inc.’s oncology portfolio.

What does the Trodelvy trial miss reveal about Gilead’s oncology outlook?

• Gilead Sciences Inc. announced that Trodelvy failed to meet its primary endpoint in the ASCENT-07 Phase 3 trial for first-line HR+/HER2– metastatic breast cancer.

• The study did not show a statistically significant improvement in progression-free survival compared to standard chemotherapy.

• The failure limits Trodelvy’s potential to scale into broader, high-volume breast cancer markets.

• Gilead Sciences Inc. stock slipped about 2% following the news, reflecting tempered investor expectations.

• Trodelvy remains approved for later-line breast cancer and is under investigation in several combination and monotherapy trials.

• Institutional sentiment is shifting cautiously, with a renewed focus on Gilead Sciences Inc.’s more stable HIV and liver disease franchises.

• The trial setback highlights challenges in deploying ADCs in first-line oncology settings and the rising importance of biomarker-driven strategies.