Discussion
esophageal cancer, pneumonitis, tumor, lung disease, toxicity, MSI-H, tumors, Pneumonitis
ESOPHAGEAL CANCER, PNEUMONITIS, RENAL, TUMOR, LUNG DISEASE, OESOPHAGEAL CANCER, COLD, TUMORS, PNEUMONITIS
In this small pilot phase 1 study with mainly non-checkpoint inhibitor responsive tumors, dose escalation of RRx-001 (bromonitrozidine) in combination with fixed dose nivolumab for up to 12 weeks was well-tolerated and no treatment-limiting toxicity was encountered. One patient with pre-existing lung disease developed mild pneumonitis, which led to her discontinuation from the trial. Pneumonitis was not designated as a DLT since pre-existing lung disease is thought to be a risk factor for its development (A maximally tolerated dose was not established within the narrow dose range explored in the phase 1 trial. According to the protocol, it was the intention to dose the combination indefinitely until progression but, unfortunately, this was not possible due to the unavailability of nivolumab.Three unconfirmed partial responses (PRs) were observed in renal cell, cervical and esophageal cancer. Renal cell is, historically, known to be one of the tumor types where checkpoint inhibitors are effective. Previously this patient received IL-2 but did not respond so it is possible that RRx-001 contributed to the benefit that she experienced. By contrast, responses in cervical and esophageal cancer are atypical; however, the microsatellite status of these tumors is unknown, which would significantly influence the likelihood of response, since microsatellite instable-high, (MSI-H), tumors are known to be exceptionally sensitive to therapy with PD-1 immune checkpoint inhibitors (These observations deserve confirmation in a larger sample set to determine whether the combination of RRx-001 and nivolumab (or another checkpoint inhibitor) can turn cold tumors hot i.e., to generate anti-tumor immune responses in non-immunogenic tumors and for how long.