AstraZeneca: Cambridge HQ Oncology / Respiratory R&D reverse-roadshow takeaways

Research evidence excerpt

AstraZeneca: Cambridge HQ Oncology / Respiratory R&D reverse-roadshow takeaways

ic activity. AZN’s clinical argument is that when ctDNA detects ESR1 mutation, tumour

burden is typically lower than at radiographic progression, and waiting longer may allow

additional resistance mechanisms to emerge. Earlier intervention could preserve endocrine

sensitivity and delay progression. Cami's acceptable safety profile was also noted, in contrast

to some ODAC comments. We note AZN are presenting cami SERENA-6 PFS2 data on Tue June

2nd at ASCO, and we note the US approval decision has been delayed on the back of AZN

submitting further supportive analysis, including ctDNA clearance data, which AZN also

intend to present on Tue June 2nd at ASCO.

•• Camizestrant SERENA-4 for 1L hormonal Breast cancer, ESR1 all-comers, AZN sees

potential differentiation vs. ROP's persevERA trial on potency of dose tested and

potentially patient enrolment/enrichment, though the later was less clear, particularly

in metastatic de novo patients. Ahead of ROP persevERA 1L data ASCO presentation next

Tue (where we expect only 10-11% overall PFS benefit, but might differ by subgroups), AZN

noted a key question will be what % of pts are truly endo sensitive in each trial, with

enrichment for endo sensitivity likely to be important in determining efficacy. We note ROP's

lidERA adjuvant trial, where all patients are by definition endo sensitive showed strong

efficacy, but the behaviour/amount of benefit in metastatic patients in persevERA and

SERENA-4, who will have had some time to evolve resistance is less clear. We will be curious

how persevERA data looks for prior adjuvant, vs. de novo metastatic patients, and to

understand whether some patients are inherently resistant, and hence will get less benefit.