Gilead’s Trodelvy-Keytruda Proposal Advances in First-Line Triple-Negative Breast Cancer Treatment

In a significant breakthrough for cancer therapeutics, Gilead Sciences’ Trodelvy has demonstrated its superiority in a first-phase 3 trial, trial dubbed Ascent-04, by effectively prolonging the time before cancer relapse or mortality in patients with previously untreated metastatic triple-negative breast cancer (TNBC). The trial results showed that the combination of Trodelvy and Keytruda, developed by Merck & Co., outperformed Keytruda administered alongside chemotherapy for patients whose tumors express the PD-L1 protein.

Announced on a Monday, the trial findings mark a pivotal milestone for Gilead in the field of oncology. According to Gilead’s newly appointed Chief Medical Officer, Dr. Dietmar Berger, this combination offers “transformative potential” in early metastatic breast cancer treatment.

What the Ascent-04 Trial Revealed

The Phase 3 Ascent-04 trial, also referred to as Keynote-D19, designated the cutoff for PD-L1 positivity at a combined positive score of at least 10. This particular classification aligns with the criteria that led to Keytruda’s FDA approval for this setting in 2020. Notably, the result now presents Trodelvy in a favorable light against competitors in the field.

Before Trodelvy’s promising readout, a collaboration between Pfizer and Astellas for the Nectin-4 ADC Padcev alongside Keytruda had gained full FDA approval as a first-line treatment for advanced bladder cancer. Additionally, AstraZeneca and Daiichi Sankyo recently reported successful outcomes in trials for HER2-positive breast cancer, further intensifying the competition in the ADC (antibody-drug conjugate) field.

Challenges and Market Position

Despite the positive outcomes from the Ascent-04 trial, Trodelvy faces substantial obstacles. The drug is contending with the introduction of two other TROP2-targeted ADCs namely AstraZeneca and Daiichi’s Datroway in the U.S. market, as well as the Merck-partnered sacituzumab tirasemtan in China. Moreover, Trodelvy has been marred by a series of clinical setbacks, including a notable failure in previously treated non-small cell lung cancer and another unsuccessful phase 3 trial that resulted in the withdrawal of its accelerated approval in bladder cancer.

However, Gilead believes that the “significant and meaningful” improvement in progression-free survival indicated by Ascent-04 reinforces Trodelvy’s potential as a vital new treatment alternative in the first-line setting for PD-L1-positive metastatic TNBC. Although data on overall survival, a key secondary endpoint, is not yet mature, preliminary findings suggest an early sign of improvement.

Addressable Patient Population and Sales Forecasts

While existing treatment options are available, Gilead noted that more than 50% of PD-L1-positive TNBC patients do not proceed to second-line treatments. Gilead estimates the addressable patient population for Ascent-04 to be around 10,000 across the U.S. and the five major European markets (EU5) by 2030. This has led Citi analysts to adopt a bullish outlook, predicting that Trodelvy could achieve peak sales of $3.2 billion by the end of the decade, surpassing the consensus estimate of $2.9 billion.

Future Trials and Gilead’s Focus

In addition to the Ascent-04 results, Gilead anticipates further outcomes from a second phase 3 trial, Ascent-03, which is assessing Trodelvy against chemotherapy in first-line, PD-L1-negative metastatic TNBC. Additionally, the Ascent-05 study is examining the efficacy of Trodelvy in conjunction with chemotherapy as an adjuvant treatment for TNBC patients who present residual invasive disease after surgical and neoadjuvant therapy.

Despite Trodelvy’s previous status as a focal point of Gilead’s oncology pursuits, recent clinical failures have redirected investor attention towards the company’s core HIV business. The forthcoming potential launch of lenacapavir, a twice-yearly drug for pre-exposure prophylaxis (PrEP), remains keenly anticipated, along with advancements in the Arcellx-partnered CD19 CAR-T candidate anito-cel.

Conclusion

The findings from Gilead Sciences regarding Trodelvy and Keytruda underscore a significant leap forward in combating metastatic TNBC, a notoriously aggressive form of breast cancer. As Gilead engages with regulatory authorities concerning these developments, the financial implications and market potential of Trodelvy could reshape treatment protocols and improve patient outcomes in a largely underserved area of oncology.