Clinical activity of ipilimumab plus nivolumab (Ipi/Nivo) in patients (pts) with metastatic non-clear cell renal cell carcinoma (nccRCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 659-659 ◽  
Author(s):  
Ruby Gupta ◽  
Moshe Chaim Ornstein ◽  
Anita Gul ◽  
Kimberly D Allman ◽  
Jessica Ball ◽  
...  
Keyword(s):  
Clear Cell ◽  
Cleveland Clinic ◽  
Standard Of Care ◽  
Preliminary Evidence ◽  
Clinical Activity ◽  
Line Treatment ◽  
Cell Renal Cell Carcinoma ◽  
Disease Response ◽  
Ecog Ps ◽  
Experienced Grade

659 Background: Ipi/Nivo is a standard of care for pts with metastatic clear cell RCC. The clinical activity of Ipi/Nivo in patients with metastatic nccRCC remains poorly defined. Methods: Metastatic nccRCC pts who were treated with Ipi/Nivo at Cleveland Clinic or UT Southwestern were retrospectively reviewed. Ipi/Nivo was administered as per CHECKMATE 214. Computed tomography imaging was obtained at baseline and every12 weeks to assess disease response per RECIST 1.1 criteria. Baseline pt characteristics, outcome to therapy and adverse effects as per CTCAE v5.0 were collected. Results: Thirteen pts with metastatic nccRCC histology who were treated with Ipi/Nivo were identified. The median age was 60 years (range, 32-81). Non clear cell histologies included adenocarcinoma of renal origin not otherwise specified (2), unclassified (3), papillary (3), chromophobe (3), translocation (1) and medullary histology (1). Nine pts had ECOG PS 0; four pts had ECOG PS 1. Eleven patients were male and two female. IMDC risk group at time of initiation of Ipi/Nivo was favorable (2 pt), intermediate (10 pts) and poor (1 pt). Nine pts received Ipi/ Nivo as first line treatment, three pts received Ipi/Nivo after prior TKI and one pt received Ipi/ Nivo as third line treatment after prior chemotherapy and nivolumab monotherapy. In total, eight pts have thus far undergone restaging scans with three pts demonstrating partial response (PR), one pt demonstrating stable disease (SD) and four pts demonstrating progressive disease (PD). Two pts experienced grade 2 diarrhea, one after 4 cycles and another after 3 cycles of Ipi/Nivo and required prednisone. One pt demonstrated grade 3 hepatotoxicity after 2 cycles of Ipi/Nivo and required prednisone and Mycophenolate Mofetil while another pt demonstrated grade 1 hepatotoxicity after 3 cycles of Ipi/ Nivo requiring prednisone. One pt experienced grade 2 pancreatitis requiring steroids after one dose of Ipi/Nivo. One pt experienced grade 2 fatigue after 1 cycle of Ipi/Nivo requiring prednisone. Conclusions: Ipi/Nivo is feasible and safe in patients with metastatic nccRCC with preliminary evidence of anti-tumor activity. Updated clinical data will be presented.

Clinical activity of ipilimumab plus nivolumab (Ipi/Nivo) in patients (pts) with metastatic non-clear cell renal cell carcinoma (nccRCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16084-e16084 ◽  
Author(s):  
Ruby Gupta ◽  
Moshe Chaim Ornstein ◽  
Anita Gul ◽  
Kimberly D Allman ◽  
Jessica Ball ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Clear Cell ◽  
Cleveland Clinic ◽  
Standard Of Care ◽  
Preliminary Evidence ◽  
Clinical Activity ◽  
Line Treatment ◽  
Related Complication ◽  
Cell Renal Cell Carcinoma ◽  
Grade 3

e16084 Background: Ipi/Nivo is a standard of care for pts with metastatic clear cell RCC. The clinical activity of Ipi/Nivo in patients with metastatic nccRCC remains poorly defined. Methods: Metastatic nccRCC pts who were treated with Ipi/Nivo at Cleveland Clinic or UT Southwestern were retrospectively reviewed. Ipi/Nivo was administered as per CHECKMATE 214. Computed tomography imaging was obtained at baseline and every 12 weeks to assess disease response per RECIST 1.1 criteria. Baseline pt characteristics, outcome to therapy and adverse effects as per CTCAE v5.0 were collected. Results: Eighteen pts with metastatic nccRCC histology who were treated with Ipi/Nivo were identified. The median age was 60 years (range, 32-81). Non clear cell histologies included adenocarcinoma of renal origin not otherwise specified (2), unclassified (3), papillary (6), chromophobe (5), translocation (1) and medullary histology (1). ECOG PS was 0 (7 pts); 1 (9 pts) and 2 (2 pts). Fourteen patients were male and four female. IMDC risk group at the time of initiation of Ipi/Nivo was favorable (2 pts), intermediate (14 pts) and poor (2 pt). Fourteen pts received Ipi/ Nivo as first line treatment, two pts received Ipi/Nivo after prior TKI and two pts received Ipi/ Nivo as third line treatment after prior chemotherapy and nivolumab monotherapy. In total, fourteen pts had restaging scans with four pts demonstrating partial response (PR 28%), two with stable disease (SD 14%) and eight with progressive disease (PD 58%). Four pts died (22%) – three from the disease and one from treatment related complication (encephalitis).Four pts experienced diarrhea- three pts (grade 2) and one pt ( grade 3) , three developed hepatotoxicity- one pt (grade 2) and two pts (grade 3), one pt each developed hypophysitis (grade 3), fatigue (grade 2) , rash (grade 2) and encephalitis (grade 3). All 100% pts required steroids, one each got infliximab and Mycophenolate Mofetil. . All 100% pts required steroids, one each got infliximab and Mycophenolate Mofetil. Conclusions: Ipi/Nivo is feasible and safe in patients with metastatic nccRCC with preliminary evidence of anti-tumor activity

Outcomes with novel combinations in non-clear cell renal cell carcinoma(nccRCC): ORACLE study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4580-4580
Author(s):  
Deepak Kilari ◽  
Aniko Szabo ◽  
Pooja Ghatalia ◽  
Tracy L Rose ◽  
Nicole Weise ◽  
...  
Keyword(s):  
Clear Cell ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
New Combination ◽  
Clinical Activity ◽  
Cell Renal Cell Carcinoma ◽  
Clear Cell Rcc ◽  
Rhabdoid Differentiation

4580 Background: Despite advances in the treatment of clear cell RCC, there is a paucity of data to guide management of nccRCC due to the heterogeneity and rarity of these tumors. The clinical activity of new combination therapies (including immunotherapy (IO), anti-vascular endothelial growth factor inhibitors (VEGF), and mammalian target of rapamycin (mTOR) inhibitors) in metastatic nccRCC is not known. Methods: In this multicenter retrospective analysis, we explored the efficacy of combination systemic therapies in patients with nccRCC. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate (ORR) assessed by investigator review. Secondary endpoints include progression- free survival (PFS), disease control rate (DCR), median duration of response (DOR), overall survival (OS), and biomarker correlates. Results: Among 66 included patients, median age was 59 yr; 60% were male and 62% white. Histologies included papillary (38%), chromophobe (17%), unclassified (24%), translocation (12%), and other (9 %). Sarcomatoid and/or rhabdoid differentiation was present in 18%, 70% had prior nephrectomy, 86% were IMDC intermediate/poor risk, 29% and 32% had liver and bone metastasis respectively. 67% received combination treatment in the first line. Comparison of outcomes based on treatment regimen is shown in the table. Conclusions: Antitumor activity was observed with novel combinations in nccRCC which warrants further prospective studies. Response rates and survival with combination therapy in this dataset remain inferior to rates seen in clear cell RCC.[Table: see text]

scholarly journals Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Vadim S. Koshkin ◽  
Pedro C. Barata ◽  
Tian Zhang ◽  
Daniel J. George ◽  
Michael B. Atkins ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Clinical Activity ◽  
Cell Renal Cell Carcinoma

scholarly journals Algorithms in the First‐Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma—Analysis Using Diagnostic Nodes

2015 ◽  
Vol 20 (9) ◽  
pp. 1028-1035 ◽  
Author(s):  
Christian Rothermundt ◽  
Alexandra Bailey ◽  
Linda Cerbone ◽  
Tim Eisen ◽  
Bernard Escudier ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Line Treatment ◽  
First Line ◽  
Cell Renal Cell Carcinoma ◽  
Diagnostic Nodes ◽  
First Line Treatment

A phase I study of oral darinaparsin in patients (pts) with advanced solid tumors (AST).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13040-e13040
Author(s):  
Luis H. Camacho ◽  
Neil N. Senzer ◽  
Wael A. Harb ◽  
John A Barrett ◽  
Christopher Charles Korth ◽  
...  
Keyword(s):  
Oral Formulation ◽  
Preliminary Evidence ◽  
Clinical Activity ◽  
Drug Discontinuation ◽  
Serum Trough ◽  
Grade 3 ◽  
Ecog Ps ◽  
Trough Levels

e13040 Background: Darinaparsin [Zinapar, ZIO-101(S-dimethylarsino-glutathione)], is a novel organic arsenic compound with in vitro and in vivo anticancer activity in tumor cell lines resistant to arsenic trioxide. An oral formulation is now available. Methods: This study used a 3+3 escalating design, dosing orally for 21 days followed by 7 days off (28 day cycle). Pts with AST refractory to standard therapy, ECOG performance score (PS) ≤ 2 and adequate organ function were treated. Study objectives were safety profile evaluation, pharmacokinetics (PK) and preliminary activity of oral darinaparsin. CTCAE v. 4.0 and RECIST 1.1 were used. Results: A total of 10 pts (8 males, 2 females), with ECOG PS 0=2, 1=8, mean age of 71 years (range: 60-81), median of prior therapies 3 (range: 1-4) were treated. A median of 2 cycles of darinaparsin was administered (range: 1-6). Dose limiting toxicities (DLT) were confusion (n=1; 400 mg), cognitive disturbance (n=1; 400 mg) and encephalopathic syndrome (n=1; 300 mg), reversible with drug discontinuation. The highest tolerable dose was 300 mg per day. Most frequent AEs were: hypokalemia, nausea (40% each), fatigue (30%), anemia, diarrhea, hypophosphatemia, pneumonia, vomiting (20% each). Most frequent grade ≥3 AEs were: hypokalemia, hypophosphatemia (20% each). Best overall response was stable disease (at 2 cycles), observed in 5 pts: adenocarcinoma of colon (2 pts), chordoma, adenocarcinoma of small bowel and carcinoma of tongue. PK analysis of 400 mg cohort (n=4) and 300 mg cohort (n=6) resulted in Tmax at 9 hr post treatment and Cmax slightly greater than dose proportional (p<0.05). Steady-state trough levels were achieved on or before Day 5. Approximately 40 % greater Cmax was observed on D15 compared to D1 for the 300 mg cohort (p<0.05) while unchanged at 400 mg. DLTs were observed when duration of exposure was more than 7 days and serum trough levels were 800 ng/ml or above. Conclusions: Oral darinaparsin is well tolerated at the dosage of 300 mg per day for 21days in a 28 day cycle in pts with AST. Preliminary evidence of clinical activity and a predictable PK profile justify further evaluation of darinaparsin in selected indications.

ASPEN: A randomized phase II trial of everolimus versus sunitinib in patients with metastatic non-clear cell renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4590-TPS4590
Author(s):  
Andrew J. Armstrong ◽  
Susan Halabi ◽  
Tim Eisen ◽  
Walter Michael Stadler ◽  
Robert R Jones ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Case Series ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Cell Renal Cell Carcinoma ◽  
Therapeutic Decisions ◽  
Undifferentiated Histology

TPS4590 Background: Currently no level 1 evidence exists to guide therapeutic decisions in patients with metastatic non-clear cell renal cell carcinoma. Case series and retrospective analyses suggest that strategies targeting either the VEGF or mTOR/TORC1 pathways have clinical activity in papillary, chromophobe, or poorly differentiated histologic subtypes. Methods: We are conducting an international, randomized phase 2 trial of patients with metastatic non-clear cell RCC; either papillary, chromophobe, or undifferentiated histology; any Motzer risk group; and who have had no prior systemic therapy. All patients contribute tissue to an international biorepository for correlative genomic, genetic, and protein biomarker studies, along with companion longitudinal plasma and urine angiome studies. Patients are randomized to either everolimus or sunitinib (1:1) at FDA approved dosing until progression. The primary endpoint is progression free survival. Trial status: Seventy-three out of a planned 108 subjects have been enrolled at the time of abstract submission: median age 64, 59 white, 10 black, 4 unknown race, and includes 42 papillary and 31 chromophobe/undifferentiated histologies, 49 men and 22 women. Accrual is anticipated to be completed by December 2013. Accrual distribution by country is currently 43 (USA), 27 (UK), and 3 (Canada). The first DSMB meeting was conducted after 40 subjects completed at least 6 months of therapy and concluded that there were no unexpected safety signals and that the study should proceed. Tissue (primary, some metastatic, urine, plasma, whole blood) has been collected on all patients to date through the Duke Center for Human Genetics Biorepository. Clinical trial information: NCT01108445.

Clinical activity of PD1/PDL1 inhibitors in metastatic non-clear cell renal cell carcinoma (nccRCC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 482-482 ◽  
Author(s):  
Raphael Brandao Moreira ◽  
Rana R. McKay ◽  
Wanling Xie ◽  
Daniel Yick Chin Heng ◽  
Guillermo de Velasco ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Clinical Activity ◽  
Significant Activity ◽  
Cell Renal Cell Carcinoma ◽  
Treatment Naïve ◽  
Retrospective Multicenter Study

482 Background: PD1/PDL1 inhibitors have shown significant activity in the treatment of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC), but their activity in nccRCC is poorly characterized. Methods: We conducted a retrospective multicenter study of pts with metastatic nccRCC treated with PD1/PDL1 inhibitors. Baseline clinical parameters, overall response rate (ORR) by RECIST, time-to-treatment failure (TTF), and overall survival (OS) were summarized. Results: We identified 40 pts across 8 academic institutions. Fourteen (35%) had papillary histology, 10 (25%) chromophobe, 3 (8%) translocation, and 7 (18%) unclassified. Six (16%) had ccRCC with a sarcomatoid component > 30%. 20% had International Metastatic RCC Database Consortium (IMDC) favorable-risk disease, 60% intermediate, and 20% poor-risk. Ten (25%) were treatment-naïve and the majority received PD1/PDL1 monotherapy (n=30, 75%), while the remaining received a combination of PD1/PDL1 with anti-VEGF(R) or anti-CTLA4 therapy. ORR for the total cohort was 18% and 10% for PD1/PDL1 monotherapy pts (Table). With a median follow-up of 5.6 months, the overall median TTF was 4.7 months (2.9-15.9) and six-month OS was 81% (60-91%). Conclusions: PD1/PDL1 blockade resulted in some activity in pts with various nccRCC histologies. In the absence of available clinical trials, this data may support the use of PD1/PDL1 blocking agents in pts with nccRCC. [Table: see text]

Unraveling the molecular profile underpinning pancreatic tropisms in metastatic clear cell renal cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16096-e16096
Author(s):  
Nirmish Singla ◽  
Oreoluwa Onabolu ◽  
Layton Woolford ◽  
Christina Stevens ◽  
Vanina Tcheuyap ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cleveland Clinic ◽  
Metastatic Tumor ◽  
Prognostic Models ◽  
Oncologic Outcomes ◽  
Molecular Profile ◽  
Cell Renal Cell Carcinoma

e16096 Background: The tropism of cancer metastases is poorly understood yet holds prognostic value. Clear cell renal cell carcinoma (ccRCC) exhibits a broad pattern of metastases, making it an optimal model to study organotropism. Notably, when ccRCC metastasizes to the pancreas (PM) independently of other sites, it is associated with favorable outcomes in patients for unclear reasons. Here, we comprehensively analyzed the clinical and molecular profile of patients with PM. Methods: RCC patients with PM from UTSW and Cleveland Clinic were identified. Clinicopathologic data and oncologic outcomes were analyzed. Whole exome sequencing (WES), RNAseq, and histologic assessment of primary and metastatic tumors from PM patients were conducted. Results: 31 RCC patients with PM were identified. We observed remarkably favorable outcomes in our PM cohort, with a median overall survival (OS) of 10.7 years from metastatic diagnosis and a long latency between initial diagnosis and development of metastasis (median 69 months in patients who were non-metastatic at diagnosis). OS was independent of both metastatic tumor burden and known IMDC prognostic factors. We discovered that tumors from PM patients were markedly uniform and clustered together by gene expression analysis. WES and DNA copy number analyses revealed a high frequency of VHL and PBRM1 mutations, 3p loss, and 5q amplification, along with a lower frequency of 9p, 14q and 4q losses and BAP1 mutations, characteristic of indolent ccRCC. Furthermore, the genomic and histologic features of tumors from patients with PM can be recapitulated in patient-derived xenograft models. Conclusions: To our knowledge, this is the first report to unravel molecular determinants of organotropism, and we highlight that organotropism can be an independent prognostic factor. Understanding tumor heterogeneity may help refine prognostic models for metastatic RCC and hold implications for improved personalization of therapy.

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