In patients with high DKK1 expression, the trial showed a 32% higher ORR and significantly longer PFS and OS. How compelling is this biomarker-driven stratification in justifying a precision oncology approach in second-line MSS CRC?

Among patients without prior anti-VEGF exposure, the 22% higher ORR and extended PFS highlight a distinct treatment-sensitive subgroup. What are the clinical implications of this finding for real-world sequencing of therapies?

The study reports both blinded independent central review (BICR) and investigator-assessed ORRs. How should clinicians interpret the discrepancy between these measures, especially in terms of data robustness?

Leap emphasized a ‘tail population’ with durable PFS that continues to mature. In oncology trial design, how meaningful is this signal, and what could it suggest about long-term responders?

Median OS was not reached in key subgroups. How should we interpret early OS signals in ongoing Phase 2 trials, especially when event rates are still low and data are immature?

With improved ORR and PFS in two defined patient subgroups, what key elements would a registrational Phase 3 trial need to address to satisfy regulators and payers?

DKK1 is emerging as a novel target in immuno-oncology. How does blocking DKK1 intersect with angiogenesis or immune evasion in MSS CRC, and why might this target be particularly relevant for combination therapy?

Leap highlighted the potential to explore first-line treatment in CRC based on these outcomes. What considerations should guide entry into that space, and what might be the competitive or mechanistic advantage of sirexatamab there