Backbone, add-on and monotherapy
Trial-design vocabulary: the backbone is the established treatment everyone in the trial receives; the add-on is the new drug tested on top of it; monotherapy means the drug alone. Most modern approvals are add-ons to a backbone.
Testing a new drug added to standard therapy (backbone) versus the backbone alone is the fastest route to approval because it needs no head-to-head against the standard, but it means patients receive more drugs and more toxicity, and it can obscure whether the new agent could replace rather than supplement (the 'chemotherapy-free' question in CLL, lung cancer and myeloma). Single-agent activity in early trials (objective response rate as monotherapy) is the usual evidence that a drug contributes. Regulators sometimes require 'contribution of components' studies when a combination is approved without it.