ADCs Under Investigation for HER2+ MBC


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

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.

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