Nuclear Medicine

Phase 2 monotherapy arms show worse efficacy and similar or higher toxicity versus phase 3

This meta-analysis pooled 130 phase 2 and 52 phase 3 monotherapy trial arms across six solid cancers (n=6665 and 18,694). The pooled objective response rate was 7% in phase 2 versus 24% in phase 3 (p < 0.0001). Median PFS and OS were shorter in phase 2 (3.23 vs 5.43 months; 9.46 vs 14.44 months; both p ≤ 0.0001). Drug-related grade 3–4 adverse events were numerically higher in phase 2 (30% vs 25%). Authors conclude phase 2 monotherapy drug administration is generally justified as research rather than as therapeutic care. 1

Registered DMT/ayahuasca trials are early-phase, safety-focused studies

This scoping review identified 26 registered interventional trials of DMT, ayahuasca, and harmine. Most trials were phase I, enrolled medically and psychiatrically healthy adults, and prioritized acute safety and physiological monitoring. Published reports emphasize tolerability, administration route, and mechanistic readouts rather than definitive clinical efficacy. A small subset of depression-focused studies provide preliminary signals that require controlled replication before clinical use. 2

Run-in phases or single-arm designs markedly reduce sample size needs in geographic atrophy trials

Using parameters from the GA Minocycline Trial (28 eyes, 28 participants), in-silico simulations compared RCTs with and without run-in phases and single-arm designs. For 2-year trials at 90% power assuming a 25% treatment effect, sample size fell from 156 (no run-in RCT) to 82, 40, and 26 with 3-, 6-, and 9-month run-ins, respectively. A 2-year single-arm trial with a 9-month run-in required 14 participants versus 26 for a matched RCT. Authors recommend exploiting GA enlargement rate stability to improve trial efficiency when appropriate. 3