AACR 2026 | Phase I trial of ABBV-368 tilsotolimod, budigalimab & nab-paclitaxel in HNSCC
Ari Rosenberg, MD, University of Chicago, Chicago, IL, discusses findings from a Phase Ib study (NCT04196283) evaluating ABBV-368, tilsotolimod, budigalimab, and nab-paclitaxel in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The combination immunotherapy and chemotherapy regimens demonstrated an acceptable safety profile and evidence of immune activation, including interferon gamma pathway upregulation. However, clinical activity was limited, with few objective responses observed. This interview took place at the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego, CA.
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Transcript
This was a phase 1b multicenter trial that we ran in recurrent metastatic head and neck cancer patients who were refractory both to immunotherapy and chemoimmunotherapy, so the treatment refractory disease setting for recurrent metastatic head and neck cancer. And this is a trial that really explored two experimental agents. One is ABBV-368, which is a humanized monoclonal antibody that targets the co-stimulatory receptor of OX40, as well as tilsotolimod, which is a toll-like receptor 9 agonist as well...
This was a phase 1b multicenter trial that we ran in recurrent metastatic head and neck cancer patients who were refractory both to immunotherapy and chemoimmunotherapy, so the treatment refractory disease setting for recurrent metastatic head and neck cancer. And this is a trial that really explored two experimental agents. One is ABBV-368, which is a humanized monoclonal antibody that targets the co-stimulatory receptor of OX40, as well as tilsotolimod, which is a toll-like receptor 9 agonist as well. This was tested in multiple combinations with budigalimab, which is a PD-1 inhibitor, as well as with nab-paclitaxel in the context of recurrent metastatic head and neck cancer. Overall, there were 30 patients enrolled, and 16 of those patients received the combination of the OX40 plus the TLR9, while an additional seven patients received the triplet of the OX40, the TLR9, and the nab-paclitaxel. And then an additional seven patients actually received the quadruplet, which is the OX40, the TLR9, the Abraxane, and budigalimab. Overall, we did find this regimen to be relatively well-tolerated, but we did not observe responses in the combination arm of the ABBV368, the OX40 agonist, with the tilsotolimod. We did have one responder in the Abraxane regimen and the Abraxane plus budigalimab plus the OX40 tilsotolimod regimen. So overall, despite the promising preclinical signals for targeting OX40 and TLR9 and recurrent metastatic head and neck cancer, this trial did not demonstrate, despite safety of the regimen, did not seem to demonstrate a clear efficacy signal to warrant further development of these particular combinations. We did do a number of evaluations of some translational work collected in order to try to understand what are some of the mechanisms of resistance, potentially, to targeting OX40 and TLR9 in this setting, particularly in the combination with PD-1 and chemotherapy. But clearly, there’s more work to be done. Despite the fact that these seem to be promising targets, we need to develop better OX40 agonists and mechanisms to modulate toll-like receptor targets in order to enhance anti-tumor immunity in the IO refractory treatment setting for recurrent metastatic head and neck cancer.
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