Dr Patel on the Exploration of Sacituzumab Govitecan in NSCLC

Sandip P. Patel, MD, medical oncologist, professor, medicine, Precision Immunotherapy Clinic, University of California, San Diego (UCSD), Moores Cancer Center, UCSD Health, discusses the utilization of sacituzumab govitecan-hziy (Trodelvy) in non–small cell lung cancer (NSCLC), highlighting trials in which the TROP2-directed antibody-drug conjugate (ADC) is being evaluated in this patient population.

Sacituzumab govitecan is a TROP2-directed ADC currently utilized in breast and bladder cancers, Patel begins, adding that TROP2 is also found on NSCLC epithelial cells, making it a promising target. ADCs, characterized by monoclonal antibodies combined with potent payloads, aim to maximize their anticancer effects and simultaneously minimize the systemic toxicity associated with the chemotherapeutic agents they contain, Patel explains. The phase 2 EVOKE-02 study (NCT05186974) is evaluating the efficacy of the combination of sacituzumab govitecan and pembrolizumab (Keytruda), a PD-1–directed immunotherapy, in patients with advanced or metastatic NSCLC, particularly in cases where immunotherapy alone may be insufficient, he explains.

The proposed mechanism of this combination involves the ADC inducing inflammation in the tumor microenvironment and facilitating the infiltration of antigen-specific T cells that synergize with the PD-1 inhibitor. This treatment approach is now also being explored in the ongoing EVOKE-03 study (NCT05609968), Patel says.

In patients with frontline NSCLC without driver mutations who have a PD-L1 score above 50%, sacituzumab govitecan plus pembrolizumab has demonstrated efficacy, Patel explains. However, this combination is also effective in patients with PD-L1 scores below 50%, a group that has historically been less responsive to PD-1–directed monotherapy, Patel emphasizes. Ongoing research, particularly in the EVOKE-03 study, is investigating sacituzumab govitecan plus pembrolizumab in the population of patients with PD-L1 scores greater than 50%. This combination is an area for future clinical investigation in patients with PD-L1 scores below 50% who lack a frontline actionable driver mutation, he states.

In clinical trials, in addition to assessing efficacy, attention to toxicity is crucial, especially when investigating combined treatments, he states. The EVOKE-02 study demonstrated manageable additive toxicities with the addition of sacituzumab govitecan to pembrolizumab, which were primarily cytopenias and gastrointestinal adverse effects. Larger studies, including the EVOKE-03 study, will further explore the potential for pulmonary toxicities, such as pneumonitis, with this combination, with consideration for the toxicity contribution of both the immunotherapy and ADC components, Patel explains.

Overall, the EVOKE-02 study shows promising activity with sacituzumab govitecan plus pembrolizumab in NSCLC, catering to patients with different PD-L1 scores. Caution should be exercised when investigating this combination in patients with PD-L1 scores less than 50%, he explains. Several other TROP2-directed ADCs are in clinical development in NSCL, he concludes.