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.
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Patritumab deruxtecan Clinical Trials – Phase I/II trial |
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HR+/Her2 negative, Her3 high or Her3 low (n=113) |
TNBC Her3 high (n=53) |
Her2+ and Her3 high (n=14) |
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ORR |
30.1% |
22.6% |
42.9% |
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PRs |
30.1% (34) |
22.6% (12) |
42.9% (6) |
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mPFS |
7.4 months |
5.5 months |
11.0 months |
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mOS |
14.6 months |
14.6 months |
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
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.
