Asco 2022 – Daiichi’s third conjugate progresses in breast and lung

Daiichi Sankyo licensed to Astrazeneca its two most advanced antibody-drug conjugates – Enhertu and datopotamab deruxtecan – but it has kept a third, patritumab deruxtecan, for itself. That project targets Her3, which is thought to play a role in certain breast and lung cancers, with new data in both presented at Asco. In the former several partial responses across the various cohorts make for encouraging reading, although with Enhertu expected to impress in a Her2-low population over the weekend patritumab’s potential in breast cancer could already be narrowing. EGFR-mutated NSCLC is the biggest hope for the project, however, with a potentially pivotal phase 2 trial already ongoing; there is evidence that Her3 expression is associated with resistance to tyrosine kinase inhibitors. Asco will see impressive response rates achieved across patients with a broad range of driver genomic alterations, and in some with no identified drivers. On safety, interstitial lung disease once again reared its head, with one death in the breast cancer trial, showing that, of the Daiichi ADCs, it is not just Enhertu that must overcome this toxicity. Her3 also needs confirming as a truly viable cancer target, of course, and such data remain some way off. 

Daiichi's third ADC: the latest results on patritumab deruxtecan
Her3-expressing metastatic breast cancer – a phase 1/2 trial 
  HR+/Her2 negative, Her3 high or Her3 low (n=113) TNBC Her3 high (n=53) Her2+ and Her3 high (n=14)
ORR 30.1% 22.6% 42.9%
PRs 30.1% (34) 22.6% (12) 42.9% (6)
mPFS 7.4 months 5.5 months 11.0 months
mOS  14.6 months 14.6 months 19.5 months


Targeting TKI resistance in advanced EGFR-mutated NSCLC – a phase 1/2 trial 
  Identified driver genomic alterations other than EGFR (n=21) Without identified driver genomic alterations (n=26)
ORR  28.60% 26.90%
CR 0 1
PRs 6 6
mDOR 9.4 months 9.6 months
Source: company press release.


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