Gilead Sciences’ TROP2-directed antibody-drug conjugate Trodelvy (sacituzumab govitecan-hziy) has a strong chance of cornering most of the market for first-line advanced or metastatic triple-negative breast cancer (TNBC) based on data from a Phase III trial presented at the American Society of Clinical Oncology in Chicago and from an additional Phase III trial in a larger TNBC subpopulation that the company aims to present later in the year.
Key Takeaways
- Gilead presented positive data at ASCO from the ASCENT-04 trial of Trodelvy and Merck’s Keytruda in first-line metastatic TNBC, and chief medical officer Dietmar Berger said the company is looking to talk to regulators “as quickly as possible” about the data.
- A key opinion leader told a press briefing that the data “really does change the game” for first-line metastatic TNBC patients.
- Together with the results of the ASCENT-03 trial, some analysts have forecast that Gilead could see as much as a doubling of Trodelvy’s sales if it wins approval in first-line disease.
The Foster City, Calif.-based drug maker presented a late-breaking abstract on May 31 at the ASCO annual meeting from ASCENT-04 (also known as KEYNOTE-D19), which combines Trodelvy with Merck & Co.’s PD-1 inhibitor Keytruda (pembrolizumab), in patients with PD-L1-positive disease. It also announced on 23 May topline results from ASCENT-03 showing Trodelvy succeeded as a monotherapy in the much larger PD-L1-negative population.
In an interview at the ASCO meeting, Gilead chief medical officer Dietmar Berger, who took the position in January following the retirement of Merdad Parsey, said the company regards the data as “practice-changing.”
“Having ASCENT-04 … and then ASCENT-03, where we also saw highly statistically significant and very clinically meaningful data, really gives us the possibility to offer Trodelvy for the entire first-line metastatic triple-negative breast cancer setting,” Berger told Scrip. “That’s basically the first time an ADC has shown that, and specifically a TROP2 ADC has shown that.”
Berger added that “you should definitely assume we’re talking to regulators as quickly as possible” about the results of the two trials.
In a 27 May press briefing ahead of the ASCO meeting, discussant and Emory University oncologist Jane Lowe Meisel called the data “potentially practice-changing.”
“We’ve seen in previous studies how sacituzumab govitecan works so well for patients with metastatic triple-negative breast cancer later on in their treatment,” she said. “And now, to see this combined with pembrolizumab and compared to chemo plus pembrolizumab with such both statistically and clinically meaningful benefits for patients, I think this really does change the game for this subgroup.”
She added that because clinicians have used both Trodelvy and Keytruda, it was a positive thing to see there were no additional toxicities, which “will help people get used to using this and feel comfortable with it once it makes its way into the clinic.”
Data Support Broad Use
In the Trodelvy/Keytruda arm, the median progression-free survival was 11.2 months, compared with 7.8 months in the chemotherapy/Keytruda arm (HR 0.65, p<0.001). The six-month PFS rate was 72% for patients receiving Trodelvy/Keytruda, versus 63% for the control arm, while the respective 12-month PFS rates were 48% and 33%. The median overall survival (OS) was not reached in either arm, though there was a positive trend in OS improvement favoring Trodelvy/Keytruda despite a high crossover rate, as 43% of patients in the chemotherapy/Keytruda arm crossed over to receive Trodelvy monotherapy in the second line.
“In first-line TNBC, five years ago, there was the introduction of checkpoint inhibitors into the space, and before that, it was all chemotherapy,” Berger said. “So there hasn’t really been any major advancement in this space for a long time.”
As ASCENT-04 investigator and Dana-Farber Cancer Institute oncologist Sara Tolaney pointed out during the press briefing, TNBC makes up about 15% of all breast cancers, and among that subpopulation about 40% of patients are PD-L1-positive.
The announcement of positive results from the ASCENT-03 trial, which tested Trodelvy monotherapy in first-line patients with PD-L1-negative disease, could thus help to significantly expand the drug’s reach in TNBC. The drug maker said the trial showed a statistically significant and clinically meaningful difference in PFS for Trodelvy over chemotherapy, but did not release numerical data, while OS data were still immature.
Leerink Partners analyst Daina Graybosch said that cornering the PD-L1-positive and PD-L1-negative markets could significantly increase revenues from the drug.
“We estimate that the combined 1L opportunity could more than double Trodelvy’s current 2/3L market, or the great bulk of its ~$1.4B sales in FY24,” Graybosch said in a 23 May note.
Cantor Fitzgerald analyst Carter Gould said in a same-day note that Wall Street expects sales of $1.4bn in 2025 and $3.1bn in 2030, while his estimate for 2030 was lower, at $1.7bn. Evaluate Pharma’s 2030 sales forecast is $2.7bn.
Trodelvy’s main competitor is AstraZeneca and Daiichi Sankyo’s Datroway (datopotamab deruxtecan-dlnk), which the FDA approved for HR-positive/HER2-negative breast cancer on Jan. 17 and is in Phase III development for TNBC patients who are not candidates for immunotherapy.