In a groundbreaking development, early data from the Phase II EVOKE-02 study has unveiled a potential game-changer in the fight against metastatic non-small cell lung cancer (NSCLC). Gilead’s Trodelvy, when combined with Merck’s cutting-edge anti-PD-1 therapy, Keytruda, has demonstrated remarkable efficacy, offering hope to patients battling this aggressive form of cancer.
However, this groundbreaking trial has also raised some concerns, as it detected worrisome safety signals. A noteworthy 18% of participants had to discontinue treatment due to side effects, and sadly, one patient lost their life due to treatment-related sepsis.
Nevertheless, the overall safety profile of Trodelvy in the EVOKE-02 study remains largely consistent with previous findings. The most commonly reported treatment-related side effects included diarrhea, anemia, and asthenia.
EVOKE-02, a multi-cohort Phase II study, enrolled a total of 224 patients and explored the combination of Trodelvy and Keytruda, with or without additional chemotherapeutic agents. Importantly, this study welcomed patients with advanced or metastatic NSCLC, regardless of their PD-L1 expression status.
The study’s primary goal was to assess the objective response rate and the occurrence of dose-limiting toxicities. Additionally, it examined crucial efficacy metrics such as overall survival, progression-free survival, disease control rate, and duration of response.
The data unveiled on Sunday stem from two patient cohorts: one with a PD-L1 tumor proportion score (TPS) of at least 50% and another with TPS below 50%. When the results from both cohorts were combined, the combination regimen showcased an impressive objective response rate of 56% and a disease control rate of 82%. Notably, the median duration of response had not yet been reached at the time of this preliminary analysis.
Bill Grossman, Senior Vice President and Therapeutic Area Head of Gilead Oncology, hailed these early findings as “encouraging.” He underscored their significance in bolstering the ongoing Phase III EVOKE-03 study, a late-stage trial that pits the combination regimen against Keytruda monotherapy in frontline treatment for metastatic, PD-L1-high NSCLC.
Trodelvy, a first-in-class antibody-drug conjugate (ADC), operates by homing in on the Trop-2 surface antigen, commonly found in various tumor types, notably breast and bladder cancers. Its precision targeting enables Trodelvy to deliver its potent payload, SN-38, a topoisomerase-I inhibitor, directly to cancer cells.
It’s worth noting that Trodelvy received its initial FDA approval in April 2020 for metastatic triple-negative breast cancer and has since garnered additional authorizations for urothelial cancer and different breast cancer types. However, it comes with a boxed warning for severe or life-threatening neutropenia and severe diarrhea.
In January 2022, Gilead forged a collaboration with Merck to explore the synergy between Trodelvy’s Trop-2-targeting mechanism and Keytruda’s established PD-L1 action in NSCLC. EVOKE-02 and EVOKE-03 represent the fruits of this partnership.
Importantly, Trodelvy has not yet secured FDA approval for NSCLC, and its use in combination with Keytruda remains investigational, as highlighted in Gilead’s Sunday announcement.