In a recent non-clinical study sponsored and funded by Blue Earth Therapeutics in collaboration with Minerva Imaging and others, the preclinical therapeutic efficacy of combining Lutetium (177Lu) rhPSMA-10.1 Injection, a PSMA-targeting radiopharmaceutical therapy, with cobimetinib, a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, for prostate cancer treatment, was evaluated.

In vitro screening

An initial in vitro screening identified the MEK inhibitor cobimetinib as one of several compounds showing synergistic efficacy with Lutetium (177Lu) rhPSMA-10.1 Injection, demonstrated by a log10 IC50 shift = 1.7525. These findings were confirmed in a follow-up screen assessing cell survival across a range of cobimetinib and Lutetium (177Lu) rhPSMA-10.1 Injection concentrations (Figure 1).

Figure 1: Survival fraction data for different cobimetinib and Lutetium (177Lu) rhPSMA-10.1 Injection concentrations. From: Caroline Foxton et al., NMB 2025

In vivo antitumor efficacy

In the 22Rv1 xenograft model, the combination of cobimetinib and Lutetium (177Lu) rhPSMA-10.1 Injection significantly suppressed tumor growth from day 13 to day 30 compared to the untreated controls and from day 17 to day 30 compared Lutetium (177Lu) rhPSMA-10.1 Injection alone (Figure 2). Similarly, the combination of cobimetinib and Lutetium (177Lu) rhPSMA-10.1 Injection significantly suppressed tumor growth versus cobimetinib alone on day 17 and day 23 (Figure 2).

Median survival was significantly improved upon combination treatment and Lutetium (177Lu) rhPSMA-10.1 injection alone and longer than with cobimetinib alone. All treatments were well tolerated with no significant weight loss.

Figure 2: Tumor growth in PSMA-expressing 22Rv1 prostate cancer xenografts. From Caroline Foxton et al., NMB 2025

These findings support the clinical investigation of cobimetinib and Lutetium (177Lu) rhPSMA-10.1 Injection combination in men with prostate cancer.

Interested in learning how Minerva Imaging can support studies of targeted radionuclide therapies in relevant PSMA-expressing or other xenograft models?

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References:

  • Caroline Foxton, Bart Cornelissen, Edward O’Neill, Bradley Waldron, Freja Pretzmann, Rikke Veggerby Grønlund, Mathias Wikke Hallund, Daniel J. Stevens (2025). A novel synergistic drug combination of a mitogen-activated extracellular signal-regulated kinase inhibitor with [177Lu]Lu-rhPSMA-10.1 for prostate cancer treatment: Results of a preclinical evaluation. Nuclear Medicine and Biology, 146-147, 109042. https://doi.org/10.1016/j.nucmedbio.2025.109042