LBA95 - Anamorelin and weight gain in patients with advanced non-small cell lung cancer (NSCLC) and cachexia: Efficacy and safety in the multinational phase III SCALA program

Background

Anamorelin is a potent, selective and well-tolerated orally available ghrelin agonist. It is marketed in Japan for the treatment of cachexia in patients with lung and gastrointestinal malignancies since early 2021. Results of two phase III trials comparing anamorelin versus placebo in cachectic non-Japanese NSCLC patients are described.

Methods

Between March 2019 and August 2022, a total of 636 subjects (318 per study) with advanced NSCLC, ECOG PS 0-2, BMI<20 kg/m², and unintentional weight loss >2% in the previous six months, were randomized 1:1 to receive 100 mg of anamorelin or a placebo orally QD for 24 weeks in two confirmatory studies with identical design (SCALA-1 and SCALA-2). Primary endpoints were changes from baseline over 12 weeks in scale body weight and in the FAACT anorexia-cachexia 5-domain symptom score (5-IASS).

Results

In both studies, anamorelin significantly increased body weight over 12 weeks compared to placebo (p<0.0001). Least square means (95% CI) treatment difference was +1.37 kg (+0.737; +2.001) for SCALA-1 and +1.30 kg (+0.720; +1.865) for SCALA-2. Changes of 5-IASS scores for anamorelin versus placebo were not significantly different in both studies. Overall, 71.2% (anamorelin) and 73.4% (placebo) of patients experienced any Treatment Emergent Adverse Event (TEAE). There was no difference when serious TEAEs, severe TEAEs, TEAEs leading to discontinuation, and TEAEs of special interest were considered. Severe hyperglycemia was reported only in two patients both receiving anamorelin (0.6%).

Conclusions

The SCALA trials demonstrate that anamorelin improves body weight in individuals with advanced NSCLC and cachexia. The observed effect on body weight is consistent with data from all eight previously conducted double-blind, placebo-controlled studies that randomized 1,696 cancer patients. The positive benefit-risk profile strongly emphasizes the therapeutic potential of anamorelin for treating unintended weight loss in patients with advanced NSCLC and cachexia.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Helsinn Healthcare SA.

Funding

Helsinn Healthcare SA.

Disclosure

D. Currow: Financial Interests, Institutional, Speaker, Consultant, Advisor: Helsinn Healthcare SA, Specialist Therapeutics; Non-Financial Interests, Institutional, Advisory Board: Helsinn Healthcare SA. S. Chessari: Other, Officer, Helsinn Healthcare SA employee: Helsinn Healthcare SA. P. Bonomi: Financial Interests, Personal, Speaker, Consultant, Advisor, Advisor & Consultant, personal financial compensation: Helsinn Healthcare SA; Financial Interests, Institutional, Financially compensated role, Clinical trial investigator, institutional financial compensation: Helsinn Healthcare SA; Financial Interests, Personal, Speaker, Consultant, Advisor, Advisor, personal compensation: Pfizer; Other, Institutional, Non remunerated activity, Manuscript preparation, author on reports for data base studies, no compensation: Pfizer; Financial Interests, Institutional, Financially compensated role, Clinical trial investigator, institutional compensation: Pfizer; Financial Interests, Financially compensated role, Chair of independent data monitoring committee, personal compensation: Roche Genentech. R. Giorgino: Other, Personal, Speaker, Consultant, Advisor: Helsinn Healthcare SA. R. Skipworth: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultant: Helsinn Healthcare SA, Actimed Therapeutics, Faraday Pharmaceuticals; Non-Financial Interests, Personal, Speaker, Consultant, Advisor, Consultant: Artelo Biosciences, Toray Pharmaceuticals.