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Mol Cancer Ther. 2018 Mar;17(3):671-676. doi: 10.1158/1535-7163.MCT-17-0673. Epub 2017 Dec 13.

Phase I Dose-Escalation Study of Anti-CTLA-4 Antibody Ipilimumab and Lenalidomide in Patients with Advanced Cancers.

Author information

1
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
4
Sarah Cannon Research Institute at HealthONE, Denver, Colorado.
5
Department of Lymphoma and Myeloma Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas.
7
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas. fjanku@mdanderson.org.

Abstract

Preclinical data suggest that combining a checkpoint 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 II dose (R2PD) and dose-limiting toxicities (DLT) of the anti-CTLA-4 antibody ipilimumab (1.5-3 mg/kg intravenously every 28 days × 4) and lenalidomide (10-25 mg 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 3 mg/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, G3 rash, G3 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. Mol Cancer Ther; 17(3); 671-6. ©2017 AACR.

PMID:
29237802
PMCID:
PMC5935561
DOI:
10.1158/1535-7163.MCT-17-0673
[Indexed for MEDLINE]
Free PMC Article

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