Sacituzumab Govitecan Meets ORR End Point in Chinese Patients With Metastatic TNBC

Sacituzumab govitecan-hziy (marketed as Trodelvy in the United States) significantly improved overall response rate (ORR) in Chinese patients with metastatic triple-negative breast cancer (mTNBC), meeting the primary end point of the phase 2b EVER-132-001 trial (NCT04454437).¹

Results showed that the antibody-drug conjugate (ADC) elicited an ORR of 38.8% per independent review committee (IRC) assessment among 80 Chinese patients with locally advanced or mTNBC who had previously received 2 or more systemic therapies, at least 1 of which having been used for metastatic disease.

Moreover, the toxicity profile with the agent proved to be comparable with what has previously been reported in other clinical trials examining its use. No new safety signals were observed.

“These topline results confirm that sacituzumab govitecan has the potential to help change the treatment outlook for people in China living with mTNBC,” Yang Shi, chief medical officer for Oncology at Everest Medicines, stated in a press release. “These data, along with the benefit seen in the global ASCENT study, support its potential as a novel treatment for patients who currently have extremely limited options.”

The single-arm, multicenter phase 2b registration clinical trial enrolled Chinese patients with histologically or cytologically confirmed TNBC who are relapsed or refractory following at least 2 prior standard-of-care chemotherapy regimens.² Patients needed to be 18 years of age or older, have an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1 criteria, and acceptable bone marrow, hepatic, and renal function.

If patients previously received a topoisomerase 1 inhibitor, had a history of or current central nervous system metastases, have Gilbert disease, are positive for human immunodeficiency virus or active hepatitis B or C infection, a history of unstable angina, myocardial infarction, or chronic heart failure, they were excluded.

Other exclusion criteria comprised a history of clinically significant active chronic obstructive pulmonary disease, an infection requiring systemic antibiotic use within 1 week of the first dose, active chronic inflammatory bowel disease, or having received high-dose systemic corticosteroids within 2 weeks before their first study dose, among others.

Study participants were administered the ADC intravenously, at a dose of 10 mg/kg on day 1 and 8 of a 21-day treatment cycle. Treatment was delivered until progressive disease, unacceptable toxicity, or withdrawn consent.

The primary end point of the trial was ORR per IRC and RECIST v1.1 criteria, and key secondary end points included duration of response, clinical benefit rate, progression-free survival, overall survival, safety and tolerability, and pharmacokinetics.

In May 2020, the China National Medical Products Administration’s Center for Drug Evaluation granted priority review to a biologics license application for sacituzumab govitecan for adult patients with locally advanced or mTNBC who have received 2 or more prior systemic therapies, at least 1 of them for metastatic disease.³

Later that year, in October 2020, the ADC was included in the updated 2020 China Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer. The following month, the first patient was dosed with sacituzumab govitecan on the trial.⁴

“Sacituzumab govitecan is an important advancement for patients as it is the first approved ADC for mTNBC worldwide and the EVER-132-001 trial is an important first step toward fulfilling our promise to patients in China with mTNBC of a potential new treatment option that can meaningfully improve their lives,” Kerry Blanchard, MD, PhD, chief executive officer of Everest Medicines, stated in a past press release.

Most recently, in April 2021, the FDA granted a full approval to sacituzumab govitecan for use in patients with unresectable locally advanced or mTNBC who previously received 2 or more systemic therapies, at least 1 of them for measurable disease.⁵

The decision was based on data from the confirmatory phase 3 ASCENT trial (NCT02574455), which showed that the ADC resulted in a median PFS of 4.8 months (95% CI, 4.1-5.8) vs 1.7 months (95% CI, 1.5-2.5) with chemotherapy (HR, 0.43; 95% CI, 0.35-0.54; P < .0001). The median OS with sacituzumab govitecan was 11.8 months (95% CI, 10.5-13.8) vs 6.9 months (95% CI, 5.9-7.6) with chemotherapy (HR, 0.51; 95% CI, 0.41-0.62; P < .0001).

References

1. Everest Medicines and Gilead Sciences jointly announce phase 2b study of sacituzumab govitecan conducted in China of patients with metastatic triple-negative breast cancer meets primary overall response rate endpoint. News release. Gilead Sciences, Inc.; November 10, 2021. Accessed November 17, 2021. https://bwnews.pr/3FsyxPs
2. Sacituzumab govitecan in Chinese patients with mTNBC of at least 2 prior treatments. ClinicalTrials.gov. Updated November 4, 2021. Accessed November 16, 2021. https://clinicaltrials.gov/ct2/show/NCT04454437
3. Everest Medicines announces China NMPA has granted priority review for sacituzumab govitecan-hziy in metastatic triple-negative breast cancer. News release. Everest Medicines; May 20, 2021. Accessed November 16, 2021. https://prn.to/3DtOFjf
4. Everest Medicines announces first patient dosed in its phase 2b registration clinical trial of Trodelvy (sacituzumab govitecan) for metastatic triple-negative breast cancer in China. News release. Everest Medicines; November 3, 2020. Accessed November 16, 2021. https://bit.ly/3FnWlnD
5. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. News release. FDA; April 7, 2021. Accessed April 7, 2021. https://bit.ly/3fOWhUD