[sam537]

Maybe I can help. Progression is usually defined by radiological endpoints (RECIST 1.1 criteria) meaning that at timepoint x the tumor stayed the same size, got smaller, or grew less than 20%. Radiological measurement is very subjective so most of these trials centralize measurement of 'target lesions' (some patients have many tumors but not all are measured in clinical trials). It is worth nothing that inside PFS not only progression is an event but also death. So if you progressed and/or died, you count as an event.

The overall response rate is a combination of complete response (tumor not measurable radiologically) and partial response (>20% reduction in size). That is a common trial endpoint.

As someone else said the Breakthrough designation is common and does not necessarily lead to efficacious drug approvals.