Purpose: To determine the maximum tolerated dose and to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors. Experimental Design: LB-100 was administered intravenously daily for 3 days in 21-day cycles in a 3+3 dose-escalation design. Results: There were 29 patient entries over 7 dose escalations. One patient stopped treatment after one dose because of an acute infection and was re-enrolled after recovery; each course was analyzed as a separate patient entry. Two patients had dose-limiting toxicity (reversible increases in serum creatinine or calculated serum creatinine clearance) at the 3.1mg/m2 level. Probable or possible study drug-related Grade 3 adverse events occurred in 6 (20.7%) patients [anemia (n=2), decreased creatinine clearance, dyspnea, hyponatremia, and lymphopenia]. Ten (50%) of 20 response-evaluable patients had stable disease for 4 or more cycles. One patient with pancreatic adenocarcinoma had a partial response noted after 10 cycles which was maintained for 5 additional cycles. The other patients achieving stable disease had one of the following: fibrosarcoma, chondrosarcoma, thymoma, atypical carcinoid of lung, or ovarian, testicular, breast (n=2), and prostate cancer. The recommended phase 2 dose of LB-100 is 2.33mg/m2 daily for 3 days every 3 weeks. Conclusions: The safety, tolerability, preliminary evidence of anti-tumor activity, and novel mechanism of action of LB-100 support its continued development alone and in combination with other therapies.
- Received September 17, 2016.
- Revision received November 30, 2016.
- Accepted December 5, 2016.
- Copyright ©2017, American Association for Cancer Research.