Gilead phase 2 EVOKE-02 study of Trodelvy in combo with Keytruda demonstrates promising clinical activity in first-line metastatic NSCLC

Gilead Sciences, Inc. announced promising early data from the global, open-label, phase 2 EVOKE-02 study evaluating Trodelvy (sacituzumab govitecan-hziy) in combination with Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) with or without platinum agents in patients with previously untreated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations. The results being presented at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) hosted by the International Association for the Study of Lung Cancer.

The preliminary analysis of the EVOKE-02 study includes results of two cohorts: Trodelvy in combination with Keytruda in first-line advanced or metastatic squamous/non-squamous NSCLC with PD-L1 tumour proportion score (TPS) = 50% (Cohort A) and TPS < 50% (Cohort B). In Cohort A (n=29), confirmed and unconfirmed objective response rate (ORR) was 69%, and disease control rate (DCR) was 86%. In Cohort B (n=32), confirmed and unconfirmed ORR was 44%, and DCR was 78%. Across both cohorts, the ORR was 56%, and DCR was 82%. Median duration of response (DoR) was not reached at the time of data cut-off, and DoR rate at six months was 88% in both cohorts.

“Patients with metastatic NSCLC continue to need novel treatment options. The data from the EVOKE-02 study gives us confidence in the clinical activity of sacituzumab govitecan in combination with pembrolizumab in first-line metastatic NSCLC patients,” said Byoung Chul Cho, MD, PhD, Professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine. “The positive response rates and duration of response across patients treated with the combination shows promise compared with historical responses to anti-PD1 monotherapy in this setting. These data support further investigation of sacituzumab govitecan as a potential IO-combination option in first-line metastatic NSCLC.”

“The EVOKE-02 trial is the first data presented from several Gilead studies dedicated to exploring Trodelvy’s potential in lung cancer,” said Bill Grossman, MD, PhD, senior vice president, therapeutic area head, Gilead Oncology. “These data are very encouraging and confirms our approach for the ongoing phase 3 EVOKE-03 study of Trodelvy in combination with Keytruda vs. Keytruda monotherapy for patients in first-line PD-L1-high metastatic NSCLC. We look forward to potentially bringing a new treatment option to previously untreated metastatic NSCLC patients.”

The safety profile of Trodelvy in combination with Keytruda in the EVOKE-02 study was consistent with the known safety of each agent. The most common any-grade TEAEs were diarrhoea (54%), anaemia (48%), and asthenia (38%). Known key safety events for Trodelvy were not increased with the addition of Keytruda. The immune related adverse events were consistent with the known safety profile of Keytruda. Discontinuation rates due to adverse events were 18%. One treatment related death was observed due to sepsis.

Gilead entered into two clinical trial collaboration and supply agreements with Merck (known as MSD outside of the United States and Canada) in January 2022 to evaluate the combination of Trodelvy and Merck’s Keytruda in the phase 2 EVOKE-02 signal-seeking study and the ongoing phase 3 EVOKE-03 study in first-line NSCLC.

The use of Trodelvy for the treatment of NSCLC and the use of Trodelvy in combination with Keytruda for any use is investigational, and the safety and efficacy for these uses have not been established or approved by any regulatory agency globally.
Worldwide, more than two million people were diagnosed with lung cancer in 2020. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for up to 85% of diagnoses. It is a cancer with high Trop-2 expression (89 – 100%) and about half of NSCLC cases are diagnosed at the metastatic stage (57%), when treatment is especially difficult. Even in patients whose disease is caught early, half will eventually progress to the metastatic stage within five years. Newly diagnosed patients have several treatment options including platinum-based therapy, checkpoint inhibitors and targeted therapies.

The EVOKE-02 study is an open-label, global, multi-center, multi-cohort, phase 2 study evaluating Trodelvy in combination with Keytruda with or without chemotherapy regardless of PD-L1 expression in patients with advanced or metastatic NSCLC without actionable genomic alterations. Patients were assigned to cohorts according to disease status or PD-L1 expression. Patients were assigned to Cohorts A or B according to Tumour Proportion Score (TPS) status: Cohort A enrolled patients with squamous/non-squamous NSCLC with TPS = 50%l; Cohort B enrolled patients with squamous/non-squamous NSCLC with TPS < 50%; Patients enrolled in Cohorts A or B received the combination of Trodelvy and Keytruda.

Following enrolment in a safety run-in cohort, patients will be enrolled in Cohorts C or D according to disease status for carboplatin combinations.

Cohort C enrolled patients with non-squamous NSCLC with any PD-L1 expression level.

Cohort D enrolled patients with squamous NSCLC with any PD-L1 expression level.

Patients enrolled in Cohorts C or D received Trodelvy plus KEYTRUDA plus platinum agent.

The primary endpoints are objective response rate (ORR) as assessed by independent review per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) and percentage of participants experiencing dose-limiting toxicities (DLTs) per dose level in the safety run-in cohorts. Additional efficacy measures include progression-free survival (PFS), overall survival (OS), duration of response (DoR) and disease control rate (DCR).

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumour types, including in more than 90% of breast and bladder cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.

Trodelvy is approved in almost 50 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.

Trodelvy is also approved in the US and the European Union to treat certain patients with pre-treated HR+/HER2- metastatic breast cancer. In the US, Trodelvy also has accelerated approval for treatment of certain patients with second-line metastatic urothelial cancer (UC). Trodelvy is also being developed for potential investigational use in other TNBC, HR+/HER2- and metastatic UC populations, as well as a range of tumour types where Trop-2 is highly expressed, including metastatic non-small cell lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people.

Optimize Your trial insights with Clival Database.

Are you exhausted from the uncertainty of trial insights pricing? Clival Database ensures the clarity in the midst of the global scenario for clinical trials to you.

Clival Database is one of the best databases that offers an outstanding number of clinical trial data in terms of 50,000+ molecules and from primary regulatory markets as well as new entrants like Indian and Chinese markets.

With Clival, you get accurate positioning of historical sales data, patent database, company profiling, safety & efficacy, and prediction of launch of new innovative molecules helping you to align your research and driving down the cost.

To add value, we further break down our analytics for you so that improving your operational effectiveness; optimizing your clinical trials; and offering you accurate and high-quality data at lowest possible prices becomes possible.

Elevate your trial success rate with the cutting-edge insights from Clival database.

Check it out today and make more informed sourcing decisions! Learn More!