This randomized, double-blind (DB), placebo-controlled, phase 2 study assessed the efficacy and safety of fulranumab as a pain therapy adjunctive to opioids in terminally ill cancer patients. Ninety-eight patients were randomized (2:1) to receive one subcutaneous injection of fulranumab (9 mg) or placebo in the 4-week DB phase. Seventy-one (72%) patients entered the 48-week open-label extension phase and were administered 9 mg of fulranumab every 4 weeks. The study failed to demonstrated efficacy at the end of the DB phase (primary endpoint, mean [SD] change in average cancer-related pain intensity was -.8 (1.26) for fulranumab and -.7 (1.56) for placebo; P = .592). However, potential benefit is suggested based on secondary endpoints (30% responder rate [P = .020], Brief Pain Inventory-Short Form [BPI-SF] pain intensity subscale [P = .003], and pain interference subscale [P = .006]). The most commonly reported treatment-emergent adverse events were (fulranumab vs placebo): asthenia (16% vs 10%), decreased appetite (12% vs 6%), fatigue (10% vs 0%), and malignant neoplasm progression (10% vs 0%). Although no differences were seen between fulranumab and placebo groups on the primary endpoint, improvements in BPI-SF pain subscale scores and responder rates support further research of anti-nerve growth factor therapy in cancer-related pain. PERSPECTIVE: Efficacy and safety of fulranumab as adjunctive pain therapy in terminally ill cancer patients were assessed. Results suggest that anti-NGF agents may prove to be novel additions in helping to optimize pain relief in cancer patients who fail to respond adequately to opioids and other common co-analgesics.