TROP2 Targeted Therapy: Module

CME

TROP-2–Targeted Therapy: Redefining the Therapeutic Landscape in HER2-Negative Breast Cancer

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit

Released: February 22, 2024

Expiration: February 21, 2025

Komal Jhaveri
Komal Jhaveri, MD, FACP

Activity

Progress
1 2
Course Completed

BEGONIA: Phase Ib/II Trial of Durvalumab Combinations in 1L Metastatic TNBC—Antitumor Response

Ongoing studies are investigating whether the benefit seen with ADCs can be improved when used in combination with other agents. BEGONIA is an ongoing open-label, multiarm phase Ib/II study of the anti‒PD-L1 antibody durvalumab in combination with other agents for patients with locally advanced or metastatic TNBC (NCT03742102). The combinations that will be studied on this trial include durvalumab alone or in combination with an ADC (either T-DXd or Dato-DXd), and durvalumab plus paclitaxel with or without the AKT inhibitor, capivasertib, or the anti-CD73 antibody, oleclumab.

In arm 7 of BEGONIA, patients received first-line Dato-DXd in combination with durvalumab.25 Dato-DXd plus durvalumab resulted in a confirmed ORR of approximately 79%, including a complete response rate of 9.7% and a partial response rate of 63.4%. The results with this combination are encouraging and warrant further investigations.

Select Ongoing Phase III Studies With Dato-DXd

Multiple ongoing phase III trials are investigating Dato-DXd either as a single agent or in combination with an immune-directed therapy for patients with early-stage or advanced-stage TNBC or HER2-low breast cancer. These trials include TROPION-Breast02 (NCT05374512), TROPION-Breast03 (NCT05629585), TROPION-Breast 04 (NCT06112379), and TROPION-Breast 05 (NCT06103864). All of these trials are actively recruiting patients.

Select Ongoing Phase III Studies With Sacituzumab Govitecan

Several ongoing phase III trials also are investigating sacituzumab govitecan alone or in combination with an immune-directed therapy for patients with early-stage or advanced-stage HR-positive or HR-negative breast cancer. For instance, the ASCENT-07 trial is investigating sacituzumab govitecan compared with treatment of physician’s choice earlier in the treatment course for patients with HR-positive/HER2-negative breast cancer, including patients with HER2 IHC 0 and HER2-low disease (NCT05840211). Other ongoing trials of sacituzumab govitecan in the advanced breast cancer setting include ASCENT-04 (NCT05382286) and ASCENT-03 (NCT05382299). For patients with early-stage disease, ongoing phase III trials include SASCIA (NCT04595565) and ASCENT-05 (NCT05633654).