Search This Blog

Wednesday, June 8, 2022

Asco 2022 – looking beyond Enhertu in Her2-low cancer

 Enhertu continues to show that it can hit Her2-expressing cancer cells that other drugs cannot reach, priming the Daiichi Sankyo and Astrazeneca asset for dominance across the Her2 space. That means serious competition for players in what now must be called Her2 high. Roche has the most to lose here, although newer products will also suffer – the launch of Seagen’s Her2 kinase inhibitor Tukysa has already been stopped in its tracks after a mere two years by Enhertu’s arrival. In the newly defined Her2-low space there will also be repercussions. The impressive Destiny-Breast04 data likely consign Gilead’s Trodelvy to a last-resort option, given this ADC’s weaker showing in Tropics-02. What of others eyeing this niche? Not many active trials can be found on clinicaltrials.gov of agents specifically going after Her2 low. Most are ADCs – step forward again Seagen, which paid $200m up front for ex-Asia rights to Remegen’s Her2-targeted ADC, disitamab vedotin. Meanwhile, a trispecific from Sanofi and a radiotherapeutic from Bayer provide different mechanistic approaches to watch. Safety is Enhertu’s weak spot so there is room for improvement here; on efficacy, though, a high bar has been set.

Aiming low: selected active trials seeking Her2-low patients
Project Mechanism Company Details 
Disitamab vedotin (RC48)Anti-Her2 ADCSeagen/RemegenRemegen has a ph3 breast cancer trial ongoing in China recruiting Her2 low only; Seagen has said it plans to start a ph3 in Her2 low
Zanidatamab + evorpaceptAnti-Her2 MAbZymeworks + ALX OncologyPh1/2 trial has Her2-low cohort
MRG002Anti-Her2 ADCShanghai MiracogenPh2 breast cancer trial ongoing in China recruiting Her2 low only
Cinrebafusp alfa (PRS-343)Anti-Her2 x 4-1BB bispecificPierisA ph2 gastric or GEJ adenocarcinoma trial has a Her2-low cohort (Tukysa combo)
Trastuzumab duocarmazine (SYD985) Anti-Her2 ADCByondis/MedacPh1 trial has a Her2-low cohort 
SAR443216Anti-CD3xCD28xHER2 trispecific Sanofi Ph1b trial has Her2-low cohorts
BAY2701439Thorium-227-Her2 MAb conjugate BayerPh1 trial has a Her2-low cohort 
IBI315Her2xPD-1 bispecific Innovent Ph1 trial possibly has Her-low cohort, company has said it intends to move into Her2 low
Runimotamab (RG6194)Her2xCD3 bispecific Roche Potential for low Her2 cohort in large phase 1 trial (Her2 criteria undefined)
ARX788Anti-Her2 ADCAmbrx Ph1b has a Her2-low cohort 
A166Anti-Her2 ADCSichuan Kelun/SorrentoPh1/2 trial allows low Her2 expression 
Source: clinicaltrials.gov, company communications, Evaluate Pharma & Journal of Clinical Oncology.

https://www.evaluate.com/vantage/articles/events/conferences-snippets/asco-2022-looking-beyond-enhertu-her2-low-cancer

No comments:

Post a Comment

Note: Only a member of this blog may post a comment.