Daiichi’s Patritumab, its third ADC making headway in HER3 expressing metastatic Breast Cancer

1. ASCO 2022: Daiichi’s Patritumab Highlight
Results from the phase I/II study of patritumab deruxtecan, a HER3-directed
antibody-drug conjugate (ADC), in patients with HER3-expressing metastatic
breast cancer (MBC)
Patritumab deruxtecan (HER3-DXd) is one of three lead DXd Daiichi Sankyo ADCs
in the oncology pipeline. Designed using Daiichi Sankyo’s proprietary DXd ADC
technology, patritumab deruxtecan comprises a fully human anti-HER3 IgG1
monoclonal antibody attached to topoisomerase I inhibitor payload (an exatecan
derivative, DXd) via a stable tetrapeptide-based cleavable linker.
At a median follow-up of 31.9 months (range, 15-56), the objective response rate
(ORR) was 30.1% in patients with HER3-high or HER3-low, HR-positive/HER2-
negative MBC. All responses were partial responses (PR). The median duration of
response (DOR) in this cohort was 7.2 months, with the median progression-free
survival (PFS) was 7.4 months, and the median overall survival (OS) was 14.6
months.
In patients with HER3-high metastatic TNBC, ORR was 22.6%, and all responders
had PR. The median DOR was 5.9 months, with a median PFS of 5.5 months and a
median OS of 14.6 months.
In patients with HER3-high, HER2-positive MBC, the ORR was 42.9%, and again all
responses were partial. The median DOR was 8.3 months with a median PFS of
11.0 months and median OS of 19.5 months.
“Results from this trial show that patritumab deruxtecan produces clinically
meaningful and durable antitumor activity in patients and further study is
warranted to further evaluate the efficacy and safety of this HER3-directed ADC
across patients with HR-positive/HER2-negative, HER2-positive, and TNBC.” –
Expert Opinion 1
“Of course this begs the question of where we go from here but clearly ADCs are
the BOMB - huge advance in chemo delivery.” – Expert Opinion 2
“Exciting clinical benefit rate across all breast cancer subtypes. The future looks
bright.”- – Expert Opinion 3
CONCLUSION

2. Daiichi Sankyo has developed three ADCs, out of which it licensed two ADCs to
AstraZeneca – but has kept the third, patritumab deruxtecan breast cancer, for
itself. The drug has been granted Breakthrough Designation from the FDA to treat
patients with metastatic or locally advanced EGFR-mutated non–small cell lung
cancer (NSCLC). The results presented at ASCO 2022 show the drug’s potential in
metastatic Breast Cancer.
The anti-Her3 space is focusing on Hummingbird Bioscience’s HMBD-001, which
recently went into the clinic in HER3-positive solid tumors. GSK’s GSK2849330 has
also produced intriguing results in NRG1 fusion cancers but is not currently listed
on the company’s pipeline. Moreover, Merus’s Her2/Her3-targeting bispecific,
zenocutuzumab, had significant results at ASCO 2022.
Companies- Gilead, Daiichi Sankyo, Sanofi, AstraZeneca, Eli Lilly, Radius Health,
Sermonix Pharmaceuticals, Roche, Veru Pharma, and others.
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