Gilead Announces Positive Results from Two Clinical Trials of First-in-Class Trop-2 ADC Trodelvy

▎WuXi

Edited by Kant Content Team

Recently, Gilead Sciences announced positive results from two clinical trials of its Trop-2-targeted antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan). The results include new data from the phase 3 TROPiCS-02 trial in patients with advanced HR+/HER2- breast cancer, as well as promising early data from the phase 2 EVOKE-02 trial evaluating Trodelvy in combination with the PD-1 inhibitor Keytruda (pembrolizumab) as a first-line treatment for metastatic non-small cell lung cancer (NSCLC).

Trop-2 is highly expressed in various human epithelial cancers, including breast cancer, lung cancer, gastric cancer, colorectal cancer, pancreatic cancer, prostate cancer, cervical cancer, head and neck cancer, and ovarian cancer, among others. The overexpression of Trop-2 plays a critical role in tumor growth. Moreover, high expression of Trop-2 has been found to correlate with more aggressive disease and poor prognosis in several cancers, such as breast cancer.

Trodelvy is a "first-in-class" ADC targeting Trop-2.Trodelvy is designed to link the topoisomerase inhibitor SN-38 to a monoclonal antibody through a hydrolysable linker. This unique combination enables the potent active SN-38 to be delivered to cells and the microenvironment expressing Trop-2.

Currently, Trodelvy has been approved for three indications in the United States, including triple-negative breast cancer,HR+/HER2- Breast CancerAnd urothelial carcinoma. In addition to the approved indications mentioned above, Trodelvy is also being developed for other potential uses, such as for the treatment of metastatic NSCLC, metastatic small cell lung cancer, head and neck cancer, and endometrial cancer.

The TROPiCS-02 study, whose results were recently published, is a global, multicenter, open-label Phase 3 clinical trial. A total of 543 patients with inoperable locally recurrent or metastatic HR+/HER2- breast cancer were enrolled. These patients had previously received at least one endocrine therapy and 2-4 prior chemotherapy regimens for metastatic disease.

Progression-Free Survival (PFS) was the primary endpoint of this study, as reported in previously released data.The median PFS for the Trodelvy group and the control group receiving single-agent chemotherapy were 5.5 months and 4.0 months, respectively.(HR: 0.66, 95% CI: 0.53-0.83, p=0.0003). The newly released final analysis results show,Compared to single-agent chemotherapy, Trodelvy can extend patients' overall survival (OS).The median OS for patients in the Trodelvy group was 14.4 months, compared to 11.2 months in the control group.(HR: 0.79, 95% CI: 0.65–0.96, p=0.02). The safety profile of Trodelvy was consistent with previous reports: 74% of patients receiving the drug experienced at least one adverse event of Grade ≥3; 34% required dose reductions due to adverse events, and 6% discontinued treatment as a result, compared to 4% in the control group.

The PFS data from this study further support the FDA's decision to approve Trodelvy for its new indication in March 2023, but more research is needed to determine the optimal use of this drug.

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Gilead Sciences signed two clinical trial collaboration and support agreements with MSD in January 2022 to evaluate the efficacy of Trodelvy in combination with Keytruda as a first-line treatment for NSCLC. Currently, a Phase 2 study, EVOKE-02, and a Phase 3 study, EVOKE-03, are ongoing.

The EVOKE-02 study, results of which were recently released, is an open-label, global, multi-center, multi-cohort Phase 2 study evaluating the efficacy of Trodelvy + Keytruda ± chemotherapy as a first-line treatment for patients with advanced or metastatic NSCLC who do not have genomic alterations treatable by targeted therapies, regardless of their PD-L1 expression levels.

Preliminary analysis results show,The confirmed and unconfirmed objective response rate (ORR) was 69% and the disease control rate (DCR) was 86% in the patient population with PD-L1 tumor proportion score (TPS) ≥50% (Cohort A, n=29). The ORR was 44% and DCR was 78% in the patient population with PD-L1 TPS <50% (Cohort B, n=32). Combined data analysis of the two cohorts showed an ORR of 56% and a DCR of 82%.The median duration of response (DoR) has not been reached at the data cutoff, and the sustained response rate at 6 months was 88% for both cohorts.

In the EVOKE-02 study, the safety of Trodelvy in combination with Keytruda was consistent with the known safety profiles of each agent. The most common treatment-emergent adverse reactions of any grade were diarrhea (54%), anemia (48%), and fatigue (38%). The known key safety events of Trodelvy did not increase with the addition of Keytruda. Immune-related adverse events were consistent with the known safety profile of Keytruda. The discontinuation rate due to adverse events was 18%. One treatment-related death due to sepsis was observed.

References:

[2] Gilead’s Phase 2 EVOKE-02 Study of Trodelvy® (sacituzumab govitecan-hziy) in Combination With KEYTRUDA® (pembrolizumab) Demonstrates Promising Clinical Activity in First-Line Metastatic Non-Small Cell Lung Cancer. Retrieved September 11，2023，from http://www.businesswire.com/news/home/20230909895203/en