A multicenter phase 1 study of PX-866 and cetuximab in patients with metastatic colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head and neck

Background This phase I, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), and antitumor activity of PX-866, a phosphatidylinositol 3-kinase inhibitor, combined with cetuximab in patients with incurable colorectal cancer or squamous cell carcinoma of the head and neck. Methods PX-866 was administered at escalating doses (6–8 mg daily) combined with cetuximab given at a 400 mg/m² loading dose followed by 250 mg/m² weekly. A “3 + 3” study design was used. Prior therapy with anti-EGFR therapies, including cetuximab, was allowed. Results Eleven patients were enrolled. The most frequent treatment-emergent adverse event was diarrhea (90.1 %), followed by hypomagnesemia (72.2 %), vomiting (72.2 %), fatigue (54.5 %), nausea (54.5 %), rash (45.5 %) and peripheral edema (40 %). No dose limiting toxicities were observed. The RP2D was 8 mg, the same as the single-agent PX-866 MTD. Best responses in 9 evaluable patients were: 4 partial responses (44.4 %), 4 stable disease (44.4 %), and 1 disease progression (11.1 %). The median progression free survival was 106 days (range: 1–271). Conclusion Treatment with PX-866 and cetuximab was tolerated with signs of anti-tumor activity. Further development of this combination is warranted.