Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors

被引：105

作者：

Apolo, Andrea B. ^{[1
]}

Nadal, Rosa ^{[1
]}

Girardi, Daniel M. ^{[1
]}

Niglio, Scot A. ^{[1
]}

Ley, Lisa ^{[1
]}

Cordes, Lisa M. ^{[1
]}

Steinberg, Seth M. ^{[2
]}

Sierra Ortiz, Olena ^{[1
]}

Cadena, Jacqueline ^{[1
]}

Diaz, Carlos ^{[1
]}

Mallek, Marissa ^{[1
]}

Davarpanah, Nicole N. ^{[1
]}

Costello, Rene ^{[1
]}

Trepel, Jane B. ^{[3
]}

Lee, Min-Jung ^{[3
]}

Merino, Maria J. ^{[4
]}

Bagheri, Mohammad Hadi ^{[5
]}

Monk, Paul ^{[6
,7
]}

Figg, William D. ^{[1
]}

Gulley, James L. ^{[1
]}

Agarwal, Piyush K. ^{[8
]}

Valera, Vladimir ^{[8
]}

Chalfin, Heather J. ^{[8
]}

Jones, Jennifer ^{[4
]}

Streicher, Howard ^{[9
]}

Wright, John J. ^{[9
]}

Ning, Yangmin M. ^{[1
]}

Parnes, Howard L. ^{[10
]}

Dahut, William L. ^{[1
]}

Bottaro, Donald P. ^{[8
]}

Lara, Primo N., Jr. ^{[11
]}

Saraiya, Biren ^{[12
]}

Pal, Sumanta K. ^{[13
]}

Stein, Mark N. ^{[12
]}

Mortazavi, Amir ^{[6
,7
]}

机构：

[1] NIH, Genitourinary Malignancies Branch, Ctr Canc Res, NCI, Bldg 10, Bethesda, MD 20892 USA

[2] NIH, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NCI, Bldg 10, Bethesda, MD 20892 USA

[3] NIH, Dev Therapeut Branch, Ctr Canc Res, NCI, Bldg 10, Bethesda, MD 20892 USA

[4] NIH, Pathol Lab, Ctr Canc Res, NCI, Bethesda, MD 20892 USA

[5] NIH, Clin Image Proc Serv, Clin Ctr, Bldg 10, Bethesda, MD 20892 USA

[6] Ohio State Univ, Coll Med, Dept Internal Med, Div Med Oncol, Columbus, OH 43210 USA

[7] Comprehens Canc Ctr, Columbus, OH USA

[8] NIH, Urol Oncol Branch, Ctr Canc Res, NCI, Bldg 10, Bethesda, MD 20892 USA

[9] NIH, Investigat Drug Branch, Canc Therapy Evaluat Program, NCI, Bldg 10, Bethesda, MD 20892 USA

[10] NIH, Div Canc Prevent, NCI, Bldg 10, Bethesda, MD 20892 USA

[11] Univ Calif Davis, Comprehens Canc Ctr, Sacramento, CA 95817 USA

[12] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA

[13] City Hope Comprehens Canc Ctr, Duarte, CA USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2020年 / 38卷 / 31期

基金：

美国国家卫生研究院;

关键词：

OPEN-LABEL; THERAPY; CANCER; MET; ANGIOGENESIS; MULTICENTER; EVEROLIMUS; BLOCKADE; SURVIVAL; PATHWAY;

D O I：

10.1200/JCO.20.01652

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

PURPOSEWe assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances.PATIENTS AND METHODSPatients received escalating doses of CaboNivo or CaboNivoIpi. The primary objective was to establish a recommended phase II dose (RP2D). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS).RESULTSFifty-four patients were enrolled at eight dose levels with a median follow-up time of 44.6 months; data cutoff was January 20, 2020. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 75% and 87% of patients treated with CaboNivo and CaboNivoIpi, respectively, and included fatigue (17% and 10%, respectively), diarrhea (4% and 7%, respectively), and hypertension (21% and 10%, respectively); grade 3 or 4 immune-related AEs included hepatitis (0% and 13%, respectively) and colitis (0% and 7%, respectively). The RP2D was cabozantinib 40 mg/d plus nivolumab 3 mg/kg for CaboNivo and cabozantinib 40 mg/d, nivolumab 3 mg/kg, and ipilimumab 1 mg/kg for CaboNivoIpi. ORR was 30.6% (95% CI, 20.0% to 47.5%) for all patients and 38.5% (95% CI, 13.9% to 68.4%) for patients with mUC. Median DoR was 21.0 months (95% CI, 5.4 to 24.1 months) for all patients and not reached for patients with mUC. Median PFS was 5.1 months (95% CI, 3.5 to 6.9 months) for all patients and 12.8 months (95% CI, 1.8 to 24.1 months) for patients with mUC. Median OS was 12.6 months (95% CI, 6.9 to 18.8 months) for all patients and 25.4 months (95% CI, 5.7 to 41.6 months) for patients with mUC.CONCLUSIONCaboNivo and CaboNivoIpi demonstrated manageable toxicities with durable responses and encouraging survival in patients with mUC and other GU tumors. Multiple phase II and III trials are ongoing for these combinations.

引用

页码：3672 / +

页数：14

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