Daniel Haldar, Assistant Professor of GI Medical Oncology at MD Anderson Cancer Center, shared a post on LinkedIn:
“Our phase I study tested binimetinib (BINI, MEK inhibitor) + hydroxychloroquine (HCQ, autophagy inhibitor) in KRAS‑mutant, previously treated metastatic pancreatic cancer.
- Rationale: dual MEK + autophagy inhibition -> therapeutic synergy in PDAC models (as shown by Channing J. Der).
- Trial design: single‑arm, open‑label dose‑escalation/expansion (NCT04132505). 34 patients enrolled Dec 2019-Aug 2024; primary endpoint was MTD using a BOIN design.
- Safety: At BINI 45 mg + HCQ 600 mg, two DLTs occurred (grade 3 CPK elevation with renal impairment and grade 3 QT prolongation). After de‑escalation, the MTD was BINI 30 mg + HCQ 600 mg twice daily due to tolerability.
- Efficacy (31 evaluable): 2 partial responses (ORR 6.5%) and 9 stable disease (DCR 35.5%). Median PFS 1.9 months; median OS 5.3 months. Overall limited clinical activity.
- Takeaway: This combo showed a challenging toxicity profile and modest activity in chemorefractory PDAC. Findings support exploring next-generation autophagy inhibitors or alternate MAPK strategies.”
Title: Phase I trial of binimetinib plus hydroxychloroquine in patients with previously treated metastatic pancreatic cancer
Authors: S Daniel Haldar, Fen Saj, So Jung Hong, Rishi Surana, Lianchun Xiao, J Jack Lee, Brandon Smaglo, Dan Zhao, Huili Zhu, Ryan Huey, Jason Willis, M Pia Morelli, Michael Overman, Florencia McAllister, Robert Wolff, Anirban Maitra, David Fogelman, Channing Der, Shubham Pant
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