Sac‑TMT NSCLC Data Moderately De‑Risks AVANZAR

Research evidence excerpt

Sac‑TMT NSCLC Data Moderately De‑Risks AVANZAR

TROP2

ADC combinations to deliver meaningful efficacy in frontline NSCLC. The key caveat is that

the comparator arm in OTL05, pembrolizumab monotherapy, is not the current standard of

care, which is chemo+immunotherapy. Therefore, while the new data materially strengthens

our confidence in the underlying biological premise of AVANZAR, and therefore increases the

probability of technical success, it does not yet resolve the key question of whether a TROP2-

directed ADC plus pembrolizumab can outperform established chemo-IO regimens in clinical

practice.

Patient mix further complicates comparisons. As noted above, the comparator arms in

OTL05 and AVANZAR differ, but the underlying patient populations also diverge in important

ways. OTL05 enrolled broadly PD-L1–positive patients without enrichment for non-squamous

histology or TROP2 expression. By contrast, AVANZAR is focused on non-squamous disease

and incorporates a TROP2 biomarker-positive primary analysis, while also including patients

across the PD-L1 spectrum, including lower expressors. From a biological perspective, this

design may be advantageous for Datroway—both through enrichment for the drug’s target and

via inclusion of patients who may derive less benefit from immunotherapy alone. However, this

potential advantage needs to be viewed in the context of a substantially tougher comparator.

AVANZAR is benchmarked against chemo-immunotherapy, whereas OTL05 compares against

pembrolizumab monotherapy, meaning the bar for demonstrating incremental benefit is

materially higher. Also, OTL05 is China-centric, while AVANZAR is global.

Waiting for AVANZAR. In conclusion, we view the OTL05 data as incrementally positive for