A randomized phase II study of nivolumab plus ipilimumab versus standard of care in previously untreated and advanced non-clear cell renal cell carcinoma (SUNIFORECAST).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS5103-TPS5103
Author(s):  
Marit Ahrens ◽  
Bernard Escudier ◽  
Ekaterini Boleti ◽  
Marc-Oliver Grimm ◽  
Marine Gross-Goupil ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell ◽  
Clear Cell ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Phase Iii ◽  
Fixed Dose ◽  
Cell Renal Cell Carcinoma ◽  
Randomized Phase Ii ◽  
Prior Systemic Therapy

TPS5103 Background: Non-clear cell renal cell carcinomas (nccRCC) are a heterogeneous group of tumors accounting for approximately 25% of RCC patients (pts.). Since most clinical trials focus on clear-cell RCC (ccRCC) only, data on treatment strategies for nccRCC are limited. The combination of Nivolumab and Ipilimumab (IO/IO) has recently been approved for treatment in RCC showing a significant improvement in overall response rate (ORR), progression free (PFS), and overall survival (OS) in intermediate and high-risk pts. compared to sunitinib in a phase-III trial. Furthermore retrospective analysis in nccRCC patients have shown promising results for IO/IO as well in these entities. Methods: In this prospective randomized phase-II multicenter European trial adults with advanced or metastatic nccRCC without prior systemic therapy are eligible. Other key inclusion criteria include: available tumor tissue, Karnofsky > 70% and measurable disease per RECIST 1.1. All histological diagnoses are reviewed by a central pathologist. The study plans to randomize ~306 pts. stratified for papillary or non-papillary non-clear cell histology and by the International Metastatic RCC Database Consortium (IMDC) risk score. Pts. will be randomized 1:1 to either i) Nivolumab 3mg/kg intravenously (IV) plus Ipilimumab 1mg/kg IV every 3 weeks for 4 doses followed by Nivolumab fixed dose 240mg IV every 2 weeks or ii) standard of care therapy according to the approved schedule. Treatment will be discontinued in case of unacceptable toxicity or withdrawal of informed consent. Pts may continue treatment beyond progression, if clinical benefit is achieved and treatment is well tolerated. Primary endpoint is the OS rate at 12 months. Secondary endpoints include OS rate at 6 and 18 months, median OS, PFS, ORR and quality of life. The trial is in progress and 122 patients (78 pts with papillary, 37 pts with non-papillary histology) have been enrolled until now. Clinical trial information: NCT03075423 .

A randomized phase II study of nivolumab plus ipilimumab versus standard of care in previously untreated and advanced non-clear cell renal cell carcinoma (SUNIFORECAST).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4597-TPS4597
Author(s):  
Marit Ahrens ◽  
Bernard Escudier ◽  
John B. A. G. Haanen ◽  
Ekaterini Boleti ◽  
Marine Gross Goupil ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Risk Groups ◽  
Fixed Dose ◽  
Cell Renal Cell Carcinoma ◽  
Randomized Phase Ii

TPS4597 Background: Non-clear cell renal cell carcinomas (nccRCC) account for approximately 25% of RCC patients (pts.). Data on treatment strategies for this heterogenous group of RCC are still limited, since most clinical trials focus on clear-cell RCC (ccRCC) histology. Recently combination therapies with immune checkpoint inhibitors (IO, avelumab or pembrolizumab) and tyrosinekinaseinhibitors (TKI) (axitinib) have been approved for treatment in RCC in all International Metastatic RCC Database Consortium (IMDC) risk groups. Additionally nivolumab and ipilimumab (IO/IO) has been approved for treatment in intermediate and high risk pts. showing a significant improvement in overall response rate (ORR), progression free (PFS), and overall survival (OS) compared to sunitinib. Moreover retrospective analysis in nccRCC pts. have shown promising results for IO-based therapies as well in these entities. Methods: In this prospective randomized phase-II multicenter European trial adults with advanced or metastatic nccRCC without prior systemic therapy are eligible. Other key inclusion criteria include: available tumor tissue, Karnofsky >70% and measurable disease per RECIST 1.1. All histological diagnoses are reviewed by a central pathologist. The study plans to randomize ̃306 pts. stratified for papillary or non-papillary non-clear cell histology and by the IMDC risk score. Pts. will be randomized 1:1 to either i) nivolumab 3mg/kg intravenously (IV) plus Ipilimumab 1mg/kg IV every 3 weeks for 4 doses followed by nivolumab fixed dose 240mg IV every 2 weeks or fixed dose 480mg IV every 4 weeks or ii) standard of care therapy according to the approved schedule. Treatment will be discontinued in case of unacceptable toxicity or withdrawal of informed consent. Pts may continue treatment beyond progression, if clinical benefit is achieved and treatment is well tolerated. Primary endpoint is the OS rate at 12 months. Secondary endpoints include OS rate at 6 and 18 months, median OS, PFS, ORR and quality of life. The trial is in progress and 214 patients (132 pts with papillary, 76 pts with non-papillary histology) have been enrolled until now. Clinical trial information: NCT03075423.

scholarly journals Temsirolimus versus Pazopanib (TemPa) in Patients with Advanced Clear-cell Renal Cell Carcinoma and Poor-risk Features: A Randomized Phase II Trial

2020 ◽  
Vol 3 (5) ◽  
pp. 687-694 ◽  
Author(s):  
Nizar M. Tannir ◽  
Pavlos Msaouel ◽  
Jeremy A. Ross ◽  
Catherine E. Devine ◽  
Anuradha Chandramohan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Clear Cell ◽  
Phase Ii Trial ◽  
Cell Renal Cell Carcinoma ◽  
Poor Risk ◽  
Randomized Phase Ii

Quadruplet regimen with capecitabine, irinotecan, oxaliplatin, and bevacizumab in chemo-naive patients with metastatic colorectal cancer: Results from the safety lead-in of QUATTRO-II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 57-57
Author(s):  
Hideaki Bando ◽  
Daisuke Kotani ◽  
Masahito Kotaka ◽  
Akihito Kawazoe ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Braf V600e ◽  
Phase Iii ◽  
Fixed Dose ◽  
Wild Type ◽  
Randomized Phase Ii ◽  
Level 1 ◽  
Grade 3

57 Background: FOLFOXIRI plus bevacizumab (BEV) is regarded as the standard of care for selected patients (pts) with metastatic colorectal cancer (mCRC), despite the high incidence of neutropenia and diarrhea. The AXEPT phase III study showed that the modified capecitabine (CAP) + irinotecan (IRI) + BEV (CAPIRI+BEV) [CAP 1600 mg/m2, IRI 200 mg/m2, and BEV 7.5 mg/kg q3wk] treatment was non-inferior to FOLFIRI+BEV, with a lower incidence of hematologic toxicity. We hypothesized that the modified CAPIRI combined with oxaliplatin (OX) and BEV (CAPOXIRI+BEV) would be more feasible than FOLFOXIRI+BEV, without compromising efficacy. Methods: The QUATTRO-II study is an open-label, multicenter, randomized phase II study. In Step 1, the recommended doses (RD) of OX and IRI were investigated as a safety lead-in. In Step 2, pts are randomized to either the RD of CAPOXIRI+BEV or FOLFOXIRI+BEV. In Step 1, four dose levels of CAPOXIRI (fixed dose of CAP 1600 mg/m2 and BEV 7.5 mg/kg plus escalated or de-escalated doses of OX and IRI, q3wk) were investigated in a 3+3 manner. A dose level of ≤ 2/6 of dose-limiting toxicity (DLT) cases was expected as the RD. Results: A total of 9 pts (3 at Level 0, 6 at Level 1) were included in Step 1. The baseline characteristics were as follows: the median age was 62 years; 6 were male; 6 presented with a left-sided tumor; 8 had a performance status of 0; all wild type/ RAS mutant/ BRAF V600E mutant were 8/1/0; and UGT1A1 wild type/*6 single hetero/*28 single hetero were 7/0/2. In Level 0 (IRI 200 mg/m2, OX 100 mg/m2), one grade 4 neutropenia and one grade 3 anorexia were observed, but without DLT. In Level 1 (IRI 200 mg/m2, OX 130 mg/m2), two grade 4 neutropenia and one grade 3 colitis were observed, with 1 DLT (febrile neutropenia) case, fully recovered without G-CSF administration. No treatment-related deaths were observed. Although dose modifications were needed in 4 of the 6 pts, no further safety concerns related to treatment continuity were observed in the 2nd or subsequent cycles. Thus, we determined that the dose administered in Level 1 is the RD for Step 2. According to the preliminary efficacy results at 8 weeks after initiating study treatment, 6 pts achieved a partial response (2 in Level 0 and 4 in Level 1). Conclusions: The RD of CAPOXIRI+BEV was 200 mg/m2 IRI, 130 mg/m2 OX, 1600 mg/m2 CAP, and 7.5mg/kg BEV. The randomized phase II Step (Step 2) of QUATTRO-II is ongoing. Clinical trial information: NCT04097444.

Results of a phase II study of atezolizumab and bevacizumab in non-clear cell renal cell carcinoma (nccRCC) and clear cell renal cell carcinoma with sarcomatoid differentiation (sccRCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 548-548 ◽  
Author(s):  
Rana R. McKay ◽  
Bradley Alexander McGregor ◽  
Kathryn Gray ◽  
John A. Steinharter ◽  
Meghara K. Walsh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Clear Cell ◽  
Collecting Duct ◽  
Cell Renal Cell Carcinoma ◽  
Histologic Subtype ◽  
Sarcomatoid Differentiation

548 Background: NccRCC and sccRCC have historically been underrepresented in clinical trials. Even with targeted therapy, most patients have inferior survival compared to clear cell renal cell carcinoma. The combination of atezolizumab and bevacizumab has demonstrated safety and efficacy in ccRCC. In this multicenter, phase II, open-label, single arm trial we evaluate the efficacy of atezolizumab and bevacizumab in patients with nccRCC and sccRCC with >20% sarcomatoid differentiation. Methods: Eligible patients had an ECOG performance status of 0-2 and may have received prior therapy. Prior PD-1/PD-L1 therapy was not allowed. Patients underwent a mandatory baseline biopsy and subsequently received atezolizumab 120 mg and bevacizumab 15 mg/kg intravenously every 3 weeks. Patients remained on therapy until radiographic progression, unacceptable adverse events, or withdrawal. The primary end point was overall response rate (ORR) as determined by RECIST version 1.1. Results: 65 patients were enrolled of whom 52 had ≥1 response assessment and were included in this analysis. 36 patients had nccRCC (papillary n=14, chromophobe n=8, unclassified RCC n=3, collecting duct n=3, translocation n=3, other n=5), and 16 patients had sccRCC. 17 patients received prior systemic therapy, 16 of whom had nccRCC. The ORR was 31% in the overall cohort (Table 1). 10 patients (19%) developed grade 3 treatment-related adverse events (AEs), half of which were immune-related. There were no grade 4-5 AEs. Conclusions: In this study, we show that therapy with atezolizumab and bevacizumab was safe and demonstrated anti-tumor activity in nccRCC and sccRCC. Further analyses will report ORR by histologic subtype and PD-L1 expression status. Analysis of tissue and blood-based biomarkers of response are ongoing. Clinical trial information: NCT02724878. [Table: see text]

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