Everolimus (E) plus bevacizumab (B) is effective first-line treatment for patients (pts) with advanced renal cell carcinoma (RCC) with papillary features (PF): Results from a phase II trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 627-627 ◽  
Author(s):  
Darren R. Feldman ◽  
Chung-Han Lee ◽  
Ana M. Molina ◽  
Andrea Knezevic ◽  
Yingbei Chen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Significant Activity ◽  
Line Treatment ◽  
First Line ◽  
Total N ◽  
Papillary Rcc ◽  
Expansion Cohort ◽  
First Line Treatment

627 Background: We previously reported on a phase II trial of E+B across various non-clear cell RCC histologies and observed significant activity among pts with papillary or unclassified RCC ( uRCC ) with PF (objective response rate [ORR] 39%, median progression-free survival [PFS] 12.9 months [m]; Voss, JCO, 2016). An expansion cohort limited to these two histologies was conducted to confirm the efficacy of E+B. Methods: E + B was administered at standard doses until progressive disease (PD) or intolerance to therapy. The current analysis included 19 pts with pRCC or uRCC with PF in the initial cohort and 20 pts in the expansion cohort (total n=39). The primary endpoint was 6 month PFS with secondary endpoints of ORR, median PFS, and overall survival (OS). Correlative analyses included next generation sequencing (NGS) from tumor and germline across >341 genes of interest. Results: Of 39 pts, 24 had uRCC with PF, 14 had papillary RCC, and 1 had translocation RCC with PF. Among 37 evaluable pts, the ORR was 35%; 43% for uRCC with PF and 23% for papillary RCC. Six-month PFS for all 39 pts was 78%; 82% for uRCC with PF and 68% for papillary RCC. Median PFS was 13.7m; 13.7m for uRCC with PF and 8.4m for papillary RCC (Table). With median followup of 17.6m, median OS is 33.9m. Toxicity with E+B was similar to previous reports. 33 of 39 pts had NGS performed and partial responses were observed across a wide spectrum of genomic alterations, including several recurrently seen in papillary RCC variants such as mutations in FH, MET, NF2, and ARID1a. Conclusions: The expansion cohort confirms the activity of E+B for pts with advanced papillary RCC or uRCC with PF with superior ORR, PFS, and OS compared to historical results with sunitinib for these histologies. E+B represents a new standard first-line treatment option for these pts. Clinical trial information: NCT01399918. [Table: see text]

A phase II trial combining tumor-targeting TP53 gene therapy with gemcitabine/nab-paclitaxel as a second-line treatment for metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4139-4139
Author(s):  
Chris Poki Leung ◽  
Minal A. Barve ◽  
Ming-Shiang Wu ◽  
Kathleen F. Pirollo ◽  
James F. Strauss ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Tp53 Gene ◽  
Phase Iii ◽  
Published Data ◽  
Line Treatment ◽  
Second Line ◽  
First Line

4139 Background: Nearly all stage IV pancreatic adenocarcinoma (PAC) patients progress after first-line treatment, and second-line options are limited. SGT-53 is an investigational product for tumor-targeted TP53 gene therapy that has completed phase Ia/Ib trials [Senser et al (2013), Mol Ther 21:1096; Pirollo et al (2016) Mol Ther 24:1697]. Methods: Here we provide an interim analysis of a Phase II trial (SGT53-02-1; NCT02340117) combining SGT-53 with gemcitabine/nab-paclitaxel (GEM/ABX). Eligible were first-line patients or those who had progressed after FOLFIRINOX (FFX) and/or gemcitabine-based therapy (second-line). In a 7-week treatment cycle, SGT-53 (3.6 mg DNA) was given once or twice weekly with GEM/ABX (1000 mg/m2/wk and 125 mg/m2/wk, respectively, for 3 of 4 weeks). Progression-free survival (PFS) and objective response rate (ORR) are primary endpoints.Overall survival (OS) and PFS are estimated by Kaplan-Meier analysis. Results: Of all evaluable patients (n=20), best response in 7 patients was determined to be partial response (PR) and 13 had stable disease (SD); none had progressive disease. In the second-line patients (n=11) there were 5 PR and 6 SD after 9 had failed FFX treatment, 3 had failed gemcitabine-based treatment and 1 had failed both. For patients with elevated CA19-9, SGT-53 + GEM/ABX resulted in marked reductions in the tumor marker. Published data for patients with PAC after therapy failure [Mita et al (2019) J Clin Med 8: 761; Portal et al (2015) Br J Cancer 113:989; Wang-Gillam et al (2016) Lancet 387:545] are shown for comparison. Notably, mPFS in our second-line patients was 7.4 months versus 3.1 months for the approved second-line therapy [Wang-Gillam et al (2016)]. This improvement in PFS exceeds the benchmark proposed to predict a clinically meaningful Phase III trial [Rahib et al (2016) Lancet Oncol 2:1209]. Conclusions: Our data suggest a clinically meaningful benefit of adding SGT-53 to GEM/ABX particularly for second-line PAC patients, most of whom had failed prior FFX treatment. Clinical trial information: NCT02340117. [Table: see text]

scholarly journals Phase II Trial of Bevacizumab in Combination With Temozolomide as First‐Line Treatment in Patients With Metastatic Uveal Melanoma

2016 ◽  
Vol 21 (3) ◽  
pp. 281 ◽  
Author(s):  
Sophie Piperno‐Neumann ◽  
Alhassane Diallo ◽  
Marie‐Christine Etienne‐Grimaldi ◽  
François‐Clément Bidard ◽  
Manuel Rodrigues ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment
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