TY - JOUR
T1 - Safety, tolerability, and preliminary activity of LB-100, an inhibitor of protein phosphatase 2A, in patients with relapsed solid tumors
T2 - An open-label, dose escalation, first-in-human, phase I trial
AU - Chung, Vincent
AU - Mansfield, Aaron S.
AU - Braiteh, Fadi
AU - Richards, Donald
AU - Durivage, Henry
AU - Ungerleider, Richard S.
AU - Johnson, Francis
AU - Kovach, John S.
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Purpose: To determine the MTD 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 þ 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 reenrolled 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 3.1 mg/m2 level. Probable or possible study drug-related grade 3 adverse events occurred in 6 (20.7%) patients [anemia (n ¼ 2), decreased creatinine clearance, dyspnea, hyponatremia, and lympho-penia]. Ten (50%) of 20 response-evaluable patients had stable disease for four or more cycles. One patient with pancreatic adenocarcinoma had a partial response noted after 10 cycles, which was maintained for five 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 ¼ 2), and prostate cancer. The recommended phase II dose of LB-100 is 2.33 mg/m2 daily for 3 days every 3 weeks. Conclusions: The safety, tolerability, preliminary evidence of antitumor activity, and novel mechanism of action of LB-100 support its continued development alone and in combination with other therapies.
AB - Purpose: To determine the MTD 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 þ 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 reenrolled 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 3.1 mg/m2 level. Probable or possible study drug-related grade 3 adverse events occurred in 6 (20.7%) patients [anemia (n ¼ 2), decreased creatinine clearance, dyspnea, hyponatremia, and lympho-penia]. Ten (50%) of 20 response-evaluable patients had stable disease for four or more cycles. One patient with pancreatic adenocarcinoma had a partial response noted after 10 cycles, which was maintained for five 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 ¼ 2), and prostate cancer. The recommended phase II dose of LB-100 is 2.33 mg/m2 daily for 3 days every 3 weeks. Conclusions: The safety, tolerability, preliminary evidence of antitumor activity, and novel mechanism of action of LB-100 support its continued development alone and in combination with other therapies.
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U2 - 10.1158/1078-0432.CCR-16-2299
DO - 10.1158/1078-0432.CCR-16-2299
M3 - Article
C2 - 28039265
AN - SCOPUS:85021707327
SN - 1078-0432
VL - 23
SP - 3277
EP - 3284
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -