ADCs Under Investigation for HER2+ MBC

Author(s):

Volkmar Mueller, MD, Prof Dr, University Medical Center Hamburg-Eppendorf ,Tiffany A. Traina, MD, Memorial Sloan Kettering Cancer Center

Expectations as to where antibody-drug conjugates in the pipeline will fit into HER2-positive metastatic breast cancer treatment algorithms.

EP: 1.Global Trends in HER2+ MBC

EP: 2.Standard Treatment Approaches in HER2+ MBC

EP: 3.Updated Data From DESTINY-Breast03 in HER2+ MBC

EP: 4.Subgroup Analyses of DESTINY-Breast03 in HER2+ MBC

EP: 5.Managing TRAEs Associated With Novel HER2+ MBC Therapies

EP: 6.T-DXd for HER2+ MBC and Interstitial Lung Disease

EP: 7.Novel Combination Approaches for HER2+ MBC

EP: 8.Updates to HER2CLIMB in HER2+ MBC

EP: 9.Updates in the Management of HER2+ MBC With Brain Metastases

Now Viewing

EP: 10.ADCs Under Investigation for HER2+ MBC

EP: 11.Therapeutic Sequencing in HER2+ MBC

EP: 12.Optimizing Therapy in HER2+ MBC Across the Globe

EP: 13.Addressing Treatment Gaps in HER2+ MBC

Volkmar Müller, MD, PhD: With all of these options we have even more coming things, new ADCs [antibody-drug conjugates] apart from trastuzumab deruxtecan. There are 2 things that might be mentioned in this perspective. Dr Traina, can you comment on that?

Tiffany A. Traina, MD: There are additional ADCs in this space. At ESMO [European Society for Medical Oncology annual meeting] there was a presentation of the TULIP trial, which is a randomized phase 3 trial for another HER2 ADC called SYD985, or trastuzumab duocarmazine. This ADC targets HER2, has a cleavable linker, and its payload is duocarmazine. This randomized study was SYD985 versus treatment of physician’s choice. The control arm was largely cytotoxic chemotherapy plus trastuzumab doublets, or capecitabine-lapatinib or capecitabine-trastuzumab were also an option. The primary end point was progression-free survival, and SYD985 had a median progression-free survival of 7 months compared to 5 months with treatment of physician’s choice; that met statistical significance and had an absolute benefit of about 2 months. Median overall survival did not meet statistical significance; numerically it was longer with SYD985 at about 20 months versus 16 months with treatment of physician’s choice.

Toxicity is a challenge with this ADC. This payload was associated with conjunctivitis and keratitis, and required intervention and monitoring with ophthalmology. All-grade conjunctivitis occurred in 38% of the population, and grade 3 or greater was around 6% in the study population. There were also 4 grade 5 events in the randomized phase 3 trial with SYD985, several pneumonitis occurrences, and 2 other respiratory events. That is one of the ADCs from the latest ESMO of interest.

Transcript edited for clarity.