Abstract A134: Atebimetinib Reduces Tumor Volume and Preserves Body Mass: A Dual Mechanism for Extended Survival in Pancreatic Cancer
Peter Vu, Vincent Chung, Gregory P. Botta, Daniel H. Ahn, Deeksha Kumaresh, Jason S. Kim, Jenny Zhang, Jason Funt, Sarah Kolitz, Vinny Hayreh, Benjamin J. Zeskind, Brett M. Hall, Igor MatushanskyAbstract
Introduction:
17.3 months median overall survival (mOS) was recently reported in 55 first-line pancreatic cancer patients treated with atebimetinib + modified gemcitabine/nab-paclitaxel (mGnP), with 84% of evaluable patients having stable or increased weight at 3 months [Chung et al, 2026]. This is notable because pancreatic cancer patients typically lose weight due to cancer-associated wasting of muscle and other tissue (cachexia). Atebimetinib, a deep cyclic inhibitor of MEK, was designed for both anti-tumor activity and body mass preservation. Preclinically, atebimetinib counteracts gene expression changes associated with cachexia and sustains body weight, including at a dose producing no tumor growth inhibition [King et al, 2024]. Given the established contribution of cachexia to cancer mortality, we investigated the relationship between body mass preservation and OS in atebimetinib-treated patients.
Methods:
Weight changes in atebimetinib-treated patients were compared with a benchmark study of patients treated with standard of care (SoC) [Fuller et al, 2025]. OS in evaluable patients with stable or increased weight at 3 months was compared to OS in those with weight loss (April 24, 2026 data cutoff). Changes in patient reported outcomes on the FAACT-Anorexia Cachexia Subscale (ACS) and the role of tumor volume reduction were assessed.
Results:
In first-line pancreatic cancer patients treated with atebimetinib+mGnP, the 84% of evaluable patients with stable or increased weight at 3 months had significantly longer OS (mOS not reached; median follow up 15.2 mo) than those with weight loss (HR=3.13; log-rank p=0.049). The percentage of patients with stable or increasing weight was significantly higher in atebimetinib-treated patients than in SoC-treated patients from the benchmark study (MWU p<0.001, Cliff's δ=+0.48). The median weight trajectory was stabilized for patients during atebimetinib treatment. Two-thirds (66%) of atebimetinib+mGnP-treated patients with low baseline ACS scores (≤37) achieved at least a 4 point increase in ACS score on treatment, across a range of RECIST responses. OS in patients with deeper tumor volume reductions (SLD≤−30%) was comparable to OS in patients with moderate tumor volume reductions (SLD 0% to −30%), while OS in patients with increased tumor volume (SLD>0%) was lower, suggesting that the presence of tumor volume reductions is more important than their depth.
Conclusions:
These findings support a dual mechanism by which atebimetinib may increase overall survival. Tumor volume reduction and preservation of body mass both predict longer OS in pancreatic cancer patients treated with atebimetinib+mGnP. Atebimetinib+mGnP is being evaluated in a Phase 3 study in first-line pancreatic cancer patients (NCT07562152).
References:
Chung V, et al. J Clin Oncol 44, 2026 (suppl 16; abstr 4013) King PJ, et al, Abstract 10-04, SCWD, 2024 Fuller S, et al, JNCI, 117:8, 2025, 1729–1732
Citation Format:
Peter Vu, Vincent Chung, Gregory P. Botta, Daniel H. Ahn, Deeksha Kumaresh, Jason S. Kim, Jenny Zhang, Jason Funt, Sarah Kolitz, Vinny Hayreh, Benjamin J. Zeskind, Brett M. Hall, Igor Matushansky. Atebimetinib Reduces Tumor Volume and Preserves Body Mass: A Dual Mechanism for Extended Survival in Pancreatic Cancer [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr A134.