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Phase 1 dose-escalation study of anti CTLA-4 antibody ipilimumab and lenalidomide in patients with advanced cancers.

Phase 1 dose-escalation study of anti CTLA-4 antibody ipilimumab and lenalidomide in patients with advanced cancers.
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Sakamuri D, Glitza IC, Betancourt Cuellar SL, Subbiah V, Fu S, Tsimberidou AM, Wheler JJ, Hong DS, Naing A, Falchook GS, Fanale MA, Cabanillas ME, Janku F,


Sakamuri D, Glitza IC, Betancourt Cuellar SL, Subbiah V, Fu S, Tsimberidou AM, Wheler JJ, Hong DS, Naing A, Falchook GS, Fanale MA, Cabanillas ME, Janku F, (click to view)

Sakamuri D, Glitza IC, Betancourt Cuellar SL, Subbiah V, Fu S, Tsimberidou AM, Wheler JJ, Hong DS, Naing A, Falchook GS, Fanale MA, Cabanillas ME, Janku F,

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Molecular cancer therapeutics 2017 12 13() pii 10.1158/1535-7163.MCT-17-0673

Abstract

Preclinical data suggest that combining a check point inhibition with immunomodulatory derivative can increase anticancer response. We designed a dose escalation study using a 3+3 design to determine the safety, maximum tolerated dose (MTD) or recommended phase 2 dose (R2PD) and dose limiting toxicities (DLT) of the anti-CTLA-4 antibody ipilimumab (1.5-3mg/kg intravenously every 28 days x 4) and lenalidomide (10-25mg orally daily for 21 of 28 days until disease progression or unacceptable toxicity) in advanced cancers. Total of 36 patients (Hodgkin lymphoma, 7; melanoma, 5; leiomyosarcoma, 4; renal cancer, 3; thyroid cancer, 3; other cancers, 14; median of 3 prior therapies) were enrolled. The MTD has not been reached and ipilimumab 3mg/kg and lenalidomide 25 mg have been declared as R2PD. DLT were grade (G) 3 rash (3 patients) and G3 pancreatitis (1 patient). G3/4 drug related toxicities other than DLT were G3 anemia (5 patients), G3 thromboembolism (2 patients), G3 thrombocytopenia, rash, hypopituitarism, G3 pneumonitis, G3 transaminitis and G4 hypopituitarism (all in 1 patient). Eight patients had tumor shrinkage per immune-related response criteria (-79% to -2%) including a PR (-79% for 7.2+ months) in a refractory Hodgkin lymphoma. Using comprehensive genomic profiling a total mutation burden (mutations/Mb) was evaluated in 17 patients, with one of the patients achieving a PR demonstrated intermediate mutation burden. In conclusion, combination of ipilimumab and lenalidomide is well tolerated and demonstrated preliminary signals of activity in patients with refractory Hodgkin lymphoma and other advanced cancers.

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