Trodelvy plus Keytruda Demonstrates Significant Efficacy in Metastatic Urothelial Cancer as a Novel Targeted-Immunotherapy Combination
Feb 20, 2022 03:20
CST Updated
03:20
Everest Medicines
Developer of Innovative Therapies
Gilead Sciences
Antiviral Drug Developer
Bladder Cancer - (Image Source: medscape.com)
News on February 19, 2022 /BioValleyBIOON/ -- According to recent reports at the 2022 American ClinicalTumorInterim results from Cohort 3 of the Phase 2 open-label TROPHY-U-01 trial (NCT03547973) presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU):In adult patients with metastatic urothelial carcinoma (mUC) whose disease has progressed after receiving platinum-based therapy and who have not been treated with immune checkpoint inhibitorsGilead’s Trop-2 targeted antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan) in combination with Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) appears to benefit patients.
UC is the most common type of bladder cancer, accounting for approximately 90% of bladder cancer cases.In Cohort 3, patients received Trodelvy in combination with Keytruda. The primary endpoint was the overall response rate (ORR), assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Results showed:With a median follow-up of 5.8 months, the ORR was 34%.(95% CI: 20.1-50.6); including 1 case of complete response and 13 cases of partial response. The clinical benefit rate (defined as complete response + partial response + stable disease for at least 6 months) was 44% (95% CI: 28.5-60.3), the 6-month progression-free survival rate was 47%, and the median duration of response (DOR) was 2 months (95% CI: 1.3-2.8).
In terms of safety, the most common treatment-related adverse events included diarrhea (76%), nausea (59%),Anemia(56%), neutropenia (44%), and asthenia (41%). 59% of patients reported grade 3 or higher treatment-emergent adverse events (TEAEs), such as diarrhea, anemia, febrile neutropenia, fatigue, and asthenia.
Trodelvy is a novel antibody-drug conjugate (ADC) targeting Trop-2, composed of a humanized IgG1 antibody targeting the TROP-2 antigen conjugated with SN-38, the metabolically active product of the chemotherapy drug irinotecan (a topoisomerase I inhibitor). Trop-2 is a marker expressed in many epithelialTumor(including NSCLC and TNBC) that is frequently expressed on the cell surface. Trodelvy selectively binds to Trop-2, delivering the anticancer agent SN-38 to selectively kill cancer cells.
April 2019,Everest MedicinesEntering into an agreement with Immunomedics,Acquired the rights to Trodelvy in Greater China, South Korea, Mongolia, and Southeast Asia.In September 2020, Gilead Sciences acquired Immunomedics for $21 billion, bringing Trodelvy into its portfolio.
In the United States, Trodelvy has been approved for 2 indications: (1) for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer in patients who have previously received at least 2 prior therapies, with at least 1 therapy for metastatic disease.Breast Cancer(TNBC) adult patients; (2) for the treatment of locally advanced or metastatic urothelial carcinoma (UC) adult patients who have previously received platinum-based chemotherapy, as well as PD-1 inhibitor or PD-L1 inhibitor therapy.
In China, Trodelvy (Sacituzumab Govitecan) was included in the 2020 edition of the "Guidelines for Standardized Diagnosis and Treatment of Advanced Breast Cancer in China" in October 2020. The guidelines were issued by the Breast Cancer Expert Committee of the National Cancer Quality Control Center, the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association, and the Chinese Anti-Cancer Association.TumorCo-authored by the Professional Committee of Drug Clinical Research. In May 2021, the National Medical Products Administration (NMPA) accepted the Biologics License Application for Trodelvy and granted it priority review.
Keytruda belongs to the PD-(L)1 tumor immunotherapy, a highly regarded class of cancer immunotherapy that aims to harness the body's own immune system to fight cancer by blocking the PD-1/PD-L1 signaling pathway to induce cancer cell death, offering potential treatment for various types.TumorThe potential.
As of now, globally, there are more than 10 PD-(L)1TumorImmune therapy has been approved for marketing, with Keytruda leading the field and multiple treatment indications already approved.Keytruda's global sales reached $17.2 billion in 2021, an increase of 20% compared to the previous year. (Bioon.com)