Design of an innovative clinical development program using randomized controlled phase 2 trial data and real-world evidence from an expanded access protocol to assess mifomelatide (TCMCB07) in GI cancer cachexia
Abstract
TPS11200
Background:
Cachexia is common in GI cancers, occurring in ~50% of patients with colorectal cancer (CRC) and up to 80% of patients with pancreatic ductal adenocarcinoma (PDAC). Resulting muscle mass and energy store depletion reduces chemotherapy tolerance, often leading to dose reductions, treatment delays/discontinuation, and poorer survival outcomes (Franko J,
Eur J Cancer
; 2022:174; Dunne RF,
J Cachexia Sarcopenia Muscle
. 2024;15:1628). Therefore, body weight preservation during chemotherapy may improve treatment effectiveness and outcomes for patients with GI cancer. The central melanocortin (MC) system, including MC3 and MC4 receptors, plays essential roles in regulating appetite, body mass, and energy homeostasis and is a logical therapeutic target to prevent and treat cachexia. Mifomelatide is a novel peptide MC3R/MC4R dual antagonist that is being studied for cancer and chemotherapy-associated weight loss. Our previously published work showed that mifomelatide was safe and effectively ameliorated cancer- and chemotherapy-associated cachexia in preclinical studies of mice, rats, and pet dogs. In a Phase 1 trial, healthy volunteers tolerated mifomelatide and did not experience vital sign or CV abnormalities or drug-related SAEs; they also experienced a modest increase in body weight and hunger compared with placebo. These findings warranted further clinical development of mifomelatide.
Methods:
The mifomelatide clinical development program is designed to…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 120 participants or records.
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