Gilead Spent $21 Billion on a Drug That Can't Crack Lung Cancer
Gilead's $21 billion ADC bet just failed its second lung cancer trial, with EVOKE-03 stopped early for futility. As rivals race ahead in first-line NSCLC, the company's solid-tumor ambitions are looking increasingly fragile.
Gilead just watched its biggest oncology bet stumble in the biggest cancer market on the planet.
The company's antibody-drug conjugate Trodelvy (sacituzumab govitecan) failed to prove itself in first-line non-small cell lung cancer, or NSCLC. The trial, called EVOKE-03, was stopped early after an independent monitoring committee concluded the drug simply wasn't working well enough. For a company that spent $21 billion acquiring Trodelvy's maker Immunomedics back in 2020, this is more than a clinical disappointment. It's a strategic reckoning.
The Trial That Got Pulled Off Life Support
EVOKE-03 was a phase III study testing Trodelvy plus Merck's blockbuster immunotherapy Keytruda (pembrolizumab) against Keytruda alone. The patients were newly diagnosed with metastatic NSCLC and had high levels of PD-L1, a protein that helps predict who responds to immunotherapy. Think of it as Gilead trying to prove that Trodelvy could supercharge the gold standard treatment.
The trial had two primary goals: show the combo keeps cancer from growing longer (progression-free survival) and show patients live longer overall (overall survival). It whiffed on both.
The combination arm showed a numerical improvement in progression-free survival, but it didn't reach statistical significance. In clinical trials, "numerical but not significant" is like losing by a field goal: close on the scoreboard, but a loss all the same. On overall survival, the monitoring committee reviewed interim data and concluded that a meaningful benefit was "unlikely" to ever materialize. Merck and Gilead pulled the plug.
Detailed numbers (medians, hazard ratios, p-values) haven't been released yet. The companies say full data will come at a future medical meeting. But the verdict is clear: adding Trodelvy to first-line immunotherapy in this population didn't move the needle enough to matter.
This Wasn't Even the First Strike
EVOKE-03 isn't Trodelvy's first swing and miss in lung cancer. An earlier trial, EVOKE-01, tested Trodelvy as a standalone treatment for patients whose NSCLC had already progressed after chemo and immunotherapy. That study also of overall survival.
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missed its primary endpoint
The numbers told a frustrating story of "almost." Median overall survival was 11.1 months with Trodelvy versus 9.8 months with docetaxel (a standard chemotherapy). The hazard ratio was 0.84 with a one-sided p-value of 0.0534, just barely outside the threshold for statistical significance. Close enough to be tantalizing; not close enough to win an FDA label.
So now Trodelvy is 0-for-2 in lung cancer. That's a problem, because NSCLC isn't just any market.
The Prize That Keeps Slipping Away
Non-small cell lung cancer is the heavyweight division of oncology. The global NSCLC therapeutics market is worth roughly $22 to $38 billion in 2025, depending on the analysis, and growing at double-digit annual rates. First-line treatment alone, where Keytruda-based regimens dominate, represents one of the single largest revenue pools in all of cancer medicine.
Gilead desperately wanted in. Trodelvy already generates strong revenue from breast cancer (approximately $1.3 billion in total 2024 sales, growing 39% year-over-year in early quarters). But breast cancer alone won't get Gilead to its stated ambition of building a $10 billion oncology franchise by the early 2030s. Lung cancer was supposed to be the bridge.
Without an NSCLC foothold, Trodelvy's ceiling looks a lot lower. Analysts had projected the drug could reach about $3.1 billion in annual sales by 2029, but that forecast was built partly on lung cancer expansion that now looks shaky at best.
Wall Street Did the Math
Investors weren't gentle. After the earlier EVOKE-01 failure, Gilead shares dropped roughly 11% in a single day. BMO Capital Markets analyst Evan Seigerman flagged growing uncertainty about Trodelvy's role in NSCLC. Leerink Partners went further, saying they saw no clear path to approval based on the EVOKE-01 data.
Gilead took a $2.4 billion impairment charge on Trodelvy in 2024, a tacit acknowledgment that the drug's value had shrunk. Management tried to frame the setback as limited rather than fatal, maintaining "very high" confidence in Trodelvy's broader development program. But confidence doesn't fill a pipeline gap.
The Competitors Aren't Waiting
While Gilead stumbles, rivals are sprinting. The TROP-2 ADC space (the same drug class as Trodelvy) is heating up fast in first-line NSCLC.
Merck and Kelun-Biotech just delivered a landmark result: their TROP-2 ADC sacituzumab tirumotecan, combined with Keytruda, reduced the risk of progression or death by 65% compared to Keytruda alone in previously untreated, PD-L1-positive NSCLC. That's the first randomized phase III win for any ADC plus immunotherapy combo in frontline lung cancer. It's exactly the kind of result Gilead needed from EVOKE-03 and didn't get.
Meanwhile, AstraZeneca and Daiichi Sankyo have their own TROP-2 ADC, datopotamab deruxtecan (Dato-DXd), already approved for a subset of NSCLC patients. Their pivotal first-line trial, AVANZAR, is expected to report results in the second half of 2027. The race for first-line lung cancer is becoming a two-horse contest, and Gilead isn't one of the horses.
So Where Does Gilead Go From Here?
Trodelvy isn't dead. It still has a strong breast cancer franchise and ongoing trials in endometrial cancer (ASCENT-GYN-01, launched in late 2024), urothelial cancer, and other solid tumors. The company also signed a deal with Tubulis in December 2024 to develop next-generation ADCs, putting up to $415 million in milestones on the line.
But the strategic math has changed. Gilead spent over $27 billion on oncology deals since 2020, including the massive Immunomedics acquisition. The pitch to investors was that Trodelvy would become a multi-tumor powerhouse, cracking breast cancer first and then expanding into lung, bladder, and gynecologic cancers. Two lung cancer failures later, that expansion story has a serious credibility problem.
The remaining pipeline opportunities are real but smaller. Endometrial cancer, ovarian cancer, and gastric cancer are meaningful markets; none of them approach the scale of first-line NSCLC. For Gilead to hit its $10 billion oncology target, it will likely need either a dramatic turnaround in lung cancer data (possible but increasingly hard to imagine) or a major new deal.
Sometimes in drug development, you bet big on a molecule and the biology just doesn't cooperate. Gilead bet $21 billion on Trodelvy being a skeleton key for solid tumors. Turns out, lung cancer changed the locks.
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