BACKGROUND: Cachexia affects the majority of patients with advanced cancer and 
is associated with reduced treatment tolerance, response to therapy, quality of 
life, and life expectancy. Cachectic patients with advanced cancer often receive 
anti-cancer therapies against their specific cancer type as a standard of care, 
and whether specific ActRII inhibition is efficacious when combined with 
anti-cancer agents has not been elucidated yet.
METHODS: In this study, we evaluated interactions between ActRII blockade and 
anti-cancer agents in CT-26 mouse colon cancer-induced cachexia model. CDD866 
(murinized version of bimagrumab) is a neutralizing antibody against the activin 
receptor type II (ActRII) preventing binding of ligands such as myostatin and 
activin A, which are involved in cancer cachexia. CDD866 was evaluated in 
association with cisplatin as a standard cytotoxic agent or with everolimus, a 
molecular-targeted agent against mammalian target of rapamycin (mTOR). In the 
early studies, the treatment effect on cachexia was investigated, and in the 
additional studies, the treatment effect on progression of cancer and the 
associated cachexia was evaluated using body weight loss or tumor volume as 
interruption criteria.
RESULTS: Cisplatin accelerated body weight loss and tended to exacerbate 
skeletal muscle loss in cachectic animals, likely due to some toxicity of this 
anti-cancer agent. Administration of CDD866 alone or in combination with 
cisplatin protected from skeletal muscle weight loss compared to animals 
receiving only cisplatin, corroborating that ActRII inhibition remains fully 
efficacious under cisplatin treatment. In contrast, everolimus treatment alone 
significantly protected the tumor-bearing mice against skeletal muscle weight 
loss caused by CT-26 tumor. CDD866 not only remains efficacious in the presence 
of everolimus but also showed a non-significant trend for an additive effect on 
reversing skeletal muscle weight loss. Importantly, both combination therapies 
slowed down time-to-progression.
CONCLUSIONS: Anti-ActRII blockade is an effective intervention against cancer 
cachexia providing benefit even in the presence of anti-cancer therapies. 
Co-treatment comprising chemotherapies and ActRII inhibitors might constitute a 
promising new approach to alleviate chemotherapy- and cancer-related wasting 
conditions and extend survival rates in cachectic cancer patients.