Introduction Melanocortins affect multiple physiological responses, including sexual behaviors. Bremelanotide is a synthetic peptide melanocortin analog of α-melanocyte-stimulating hormone that is an agonist at melanocortin receptors MC3R and MC4R. Aim To evaluate a single intranasal dose of bremelanotide for potential effects on physiological and subjective measurements of sexual arousal and desire in premenopausal women with sexual arousal disorder. Main Outcome Measures Change in vaginal pulse amplitude during neutral and erotic videos after treatment with bremelanotide or placebo and subjects’ perceptions of physiological and sexual response within 24 hours of treatment with bremelanotide or placebo. Methods Eighteen premenopausal women with a primary diagnosis of female sexual arousal disorder were randomly assigned to receive a single intranasal dose of 20 mg bremelanotide or matching placebo in a double-blind manner during the first in-clinic treatment session, and the alternate medication during the second in-clinic treatment session. During each session, subjects viewed a 20-minute neutral video followed by a 20-minute sexually explicit video. Vaginal photoplethysmography was used to monitor vaginal vasocongestion and questionnaires were used to evaluate perceptions of sexual response within the following 24-hour period. Results More women reported moderate or high sexual desire following bremelanotide treatment vs. placebo (P = 0.0114), and a trend toward more positive responses regarding feelings of genital arousal occurred after bremelanotide compared with placebo (P = 0.0833). Among women who attempted sexual intercourse within 24 hours after treatment, significantly more were satisfied with their level of sexual arousal following bremelanotide, compared with placebo (P = 0.0256). Vaginal vasocongestion did not change significantly while viewing erotic videos following bremelanotide administration compared with placebo. Conclusion This preliminary evaluation suggests the potential for bremelanotide to positively affect desire and arousal in women with female sexual arousal disorder and indicates that bremelanotide is a promising candidate for further evaluation in an at-home study.

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PT-141, a synthetic peptide analogue of alpha-MSH, is an agonist at melanocortin receptors including the MC3R and MC4R, which are expressed primarily in the central nervous system. Administration of PT-141 to rats and nonhuman primates results in penile erections. Systemic administration of PT-141 to rats activates neurons in the hypothalamus as shown by an increase in c-Fos immunoreactivity. Neurons in the same region of the central nervous system take up pseudorabies virus injected into the corpus cavernosum of the rat penis. Administration of PT-141 to normal men and to patients with erectile dysfunction resulted in a rapid dose-dependent increase in erectile activity. The results suggest that PT-141 holds promise as a new treatment for sexual dysfunction.

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Repeated fanolesomab injections at clinically useful doses does not appear to induce a strong HAMA response nor does it present a risk for serious adverse events.

TPS4143 Background: Blockade of the immune checkpoint receptor programmed death-1 (PD-1) has shown clinical benefit in multiple tumor types. Nivolumab (anti–PD-1) has demonstrated a survival advantage versus (vs) placebo in patients (pts) with advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC) (Kang YK et al. Lancet 2017;390:2461–71). Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint molecule that negatively regulates effector T-cell function and is a marker of T-cell exhaustion. Preliminary data in melanoma suggest that combining nivolumab with relatlimab (anti–LAG-3) could improve efficacy without substantially increasing toxicity vs nivolumab especially, but not exclusively, in LAG-3-expressing pts (Ascierto PA et al. Ann Oncol 2017;28(S5):LBA18). Furthermore, LAG-3 expression was as high as 33% in an analysis of solid tumors including GC (Edwards R et al. J Immunother Cancer 2017;5(S3):P510). Study CA224-060 will assess the clinical efficacy and safety of relatlimab and nivolumab with chemotherapy for first-line treatment of GC or GEJC. Methods: This is a randomized, open-label, multicenter, phase 2 study of relatlimab and nivolumab with oxaliplatin-based chemotherapy vs nivolumab with oxaliplatin-based chemotherapy. Approximately 250 adult pts with untreated, locally advanced, unresectable or metastatic GC or GEJC will be enrolled. To be randomized, pts must have tumor tissue for analysis of biomarkers, LAG-3 status, and PD-L1 combined positive score. Key exclusion criteria include HER2-positive status, untreated CNS metastases, or significant cardiovascular disease. The primary endpoint is objective response rate (ORR) using RECIST v.1.1 by blinded independent central review in LAG-3-expressing pts. Other endpoints include investigator-assessed ORR, ORR in LAG-3-negative pts, duration of response, overall survival, progression-free survival, and safety and tolerability. Efficacy signals in biomarker subgroups will be explored. Currently, 26 sites are activated with 15 randomized pts. Clinical trial information: NCT03662659.