Preliminary safety data of an ongoing phase I-II clinical study with the tumor vaccine MGN1601 in patients with advanced renal cell carcinoma.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e15157-e15157
Author(s):  
M. Tschaika ◽  
S. Weikert ◽  
E. Weith ◽  
V. Gruenwald ◽  
M. Schroff ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Study ◽  
Phase I ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Vaccine ◽  
Safety Data ◽  
Advanced Renal Cell Carcinoma ◽  
Ongoing Phase

Phase I Trial of 40-kd Branched Pegylated Interferon Alfa-2a for Patients With Advanced Renal Cell Carcinoma

2001 ◽  
Vol 19 (5) ◽  
pp. 1312-1319 ◽  
Author(s):  
Robert J. Motzer ◽  
Ashok Rakhit ◽  
Michelle Ginsberg ◽  
Karen Rittweger ◽  
Jacqueline Vuky ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Serum Concentration ◽  
Phase I ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Subcutaneous Administration ◽  
Interferon Alfa ◽  
Advanced Renal Cell Carcinoma ◽  
Grade 3 ◽  
Dose Limiting Toxicity

PURPOSE: Pegylated (40 kd) interferon alfa-2a (IFNα2a) (PEGASYS, Hoffman-La Roche, Nutley, NJ; PEG-IFN) is a modified form of recombinant human IFNα2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase I study of PEG-IFN with pharmacokinetic and pharmacodynamic evaluations was conducted in previously untreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-seven patients were enrolled onto cohorts of three or six patients. PEG-IFN was administered on a weekly basis by subcutaneous injection. The dose was escalated from 180 μg/wk to a maximum of 540 μg/wk in 90-μg increments. Serial venous blood samples were drawn to assess concentrations of PEG-IFN and two immunologic surrogates, neopterin and 2′-5′ oligoadenylate synthetase (OAS). RESULTS: The maximum-tolerated dose was determined as 540 μg/wk, because two patients experienced dose-limiting toxicity within 28 days of starting treatment. One developed serum grade 3 ALT elevation, and a second developed grade 3 fatigue. Six patients were treated at 450 μg/wk without dose-limiting toxicity. Over the course of treatment, the side-effect profile was mostly mild to moderate in intensity. Adverse events included fatigue, fever, headache, myalgia, nausea, and decreased appetite. Five patients (19%) achieved a partial response. The mean maximum serum concentration increased from 5.0 to 27 ng/mL, and mean area under the curve increased from 247 to 2,981 ng/h/mL, with dose escalation from 180 μg/wk to 540 μg/wk. Serum concentration of PEG-IFN was sustained at close to peak during the dosing interval, and steady-state was achieved in approximately 5 weeks. The immunologic surrogates, neopterin and OAS, were induced at all doses with a sustained concentration profile similar to PEG-IFN. CONCLUSION: PEG-IFN is a modified form of IFNα2a with distinct pharmacokinetic advantages and immunomodulatory and antitumor activity for patients with advanced RCC. A dose of 450 μg/wk by subcutaneous administration was determined as a suitable dose for further study. PEG-IFN is more convenient to administer than IFNα and has potential for increased efficacy, less toxicity, or both. The efficacy and toxicity of PEG-IFN will be further assessed in clinical trials and compared with IFNα.

NCI 6896: a phase I trial of vorinostat (SAHA) and isotretinoin (13-cis retinoic acid) in the treatment of patients with advanced renal cell carcinoma

2020 ◽  
Vol 38 (5) ◽  
pp. 1383-1389
Author(s):  
Ana M. Molina ◽  
Johannes C. van der Mijn ◽  
Paul Christos ◽  
John Wright ◽  
Charlene Thomas ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Retinoic Acid ◽  
Phase I ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Phase I Trial ◽  
Advanced Renal Cell Carcinoma

Efficacy and safety of cancer vaccine with 4-fold gene-modified allogeneic tumor cells: Results of the phase I/II ASET study in patients with advanced renal cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4636-4636
Author(s):  
Steffen Weikert ◽  
Viktor Grünwald ◽  
Ingo GH Schmidt-Wolf ◽  
Stefan Hauser ◽  
Kerstin Kapp ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Phase I ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Cancer Vaccine ◽  
Renal Cell ◽  
Tumor Response ◽  
Advanced Renal Cell Carcinoma ◽  
Allogeneic Tumor

4636 Background: MGN1601 was tested in the first-in-man phase I-II clinical study in patients with advanced renal cell carcinoma (RCC) who failed several previous therapy lines and had no further standard therapy available. MGN1601 consists of two active pharmaceutical ingredients in fixed combination: fourfold gene-modified allogeneic tumor cells expressing IL-7, GM-CSF, CD80 and CD154 through MIDGE vectors and a TLR-9 agonist, the immunomodulator dSLIM. Methods: The ASET study is a multicentric, single-arm phase I-II clinical trial. Clinical response was evaluated using CT scans (RECIST 1.1 or immune related Response Criteria, irRC). Efficacy data were evaluated in terms of PFS and OS for the intended to treat and the treated per protocol (TPP) populations, clinical parameters and quality of life. Immune response was determined using DTH to MGN1601, LTT assay, frequency and activation of blood cells, and mRNA, chemokine and cytotoxic T cells analysis as well as tumor tissue evaluation. Results: Nine of 19 included patients completed the TPP, the others discontinued the study earlier due to PD. Median PFS in the TPP group was 12 wks (3 months) and OS (not reached yet) 46 wks (11 months). Three patients achieved disease control (1 PR, 2 SD) after 12 wks. Two patients are continuing treatment in the extension phase and are progression free since 37 and 46 wks, respectively. Re-evaluation of tumor response data using irRC revealed 1 additional patient with a delayed tumor response 4 wks after treatment stop. Herewith, 4 out of 9 TPP patients (45%) achieved disease control. Of 7 patients receiving targeted therapy upon stop of study treatment, 4 had substantial objective responses, providing evidence that the study drug is able to render their tumors more vulnerable to subsequent therapies. Immune analysis showed trends towards increases of T-, NKT-cell and pDC frequencies and other immune parameters in those patients with clinical responses, indicating anti-tumor immunity of study treatment. Conclusions: The therapeutic cancer vaccine MGN1601 shows promising efficacy in late stage mRCC patients. Results warrant further clinical studies with MGN1601.

A multicenter, noncontrolled clinical study of sorafenib adjuvant therapy in advanced renal cell carcinoma.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e15553-e15553
Author(s):  
Dingwei Ye ◽  
Zhisong He ◽  
Yinghao Sun ◽  
Chuize Kong ◽  
Liping Xie ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Study ◽  
Adjuvant Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Advanced Renal Cell Carcinoma

Axitinib plus pembrolizumab in patients with advanced renal cell carcinoma: Long-term efficacy and safety from a phase Ib study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5080-5080
Author(s):  
Michael B. Atkins ◽  
Igor Puzanov ◽  
Elizabeth R. Plimack ◽  
Mayer N. Fishman ◽  
David F. McDermott ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Median Time ◽  
Renal Cell ◽  
Safety Data ◽  
Advanced Renal Cell Carcinoma ◽  
Efficacy And Safety ◽  
Term Efficacy

5080 Background: Axitinib (AXI) plus pembrolizumab (pembro) showed superior overall survival (OS), progression-free survival (PFS) and response rate compared with sunitinib in a randomized Phase 3 trial in advanced renal cell carcinoma (RCC). Here, we report long-term efficacy and safety data of the combination AXI/pembro from the Phase 1 trial, with almost 5 years of follow-up. Methods: 52 treatment-naïve patients with advanced RCC were enrolled between 23 September 2014 and 13 October 2015, and were treated with oral AXI 5 mg twice daily and intravenous pembro 2 mg/kg every 3 weeks. Planned treatment duration was 2 years for pembro and not limited for AXI. Based on International Metastatic Database Consortium (IMDC) criteria, 46.2%, 44.2% and 5.8% of patients were reported as having favourable, intermediate and poor risk. Results: At data cut-off date (July 3, 2019), median OS was not reached; 38 (73.1%) patients were alive. 14 (26.9%) patients had died, none were related to treatment. The probability of being alive was 96.1% (95% CI 85.2–99.0) at 1 year, 88.2% (95% CI 75.7– 94.5) at 2 years, 82.2 % (95% CI 68.5– 90.3) at 3 years, and 66.8 % (95% CI 49.1–79.5) at 4 years. Median PFS was 23.5 (95% CI 15.4–30.4) months. Median duration of response was 22.1 (95% CI 15.1–not evaluable) months. Median time on treatment with the combination AXI/pembro was 14.5 months (n=52), median time on pembro after AXI discontinuation was 9.0 months (n=10), and median time on AXI after pembro discontinuation was 7.5 months (n=11). After stopping study treatment, 22 patients received subsequent systemic therapy, including nivolumab and cabozantinib (n=6 each). Grade 3/4 AEs were reported in 38 (73.1%) patients. 20 (38.5%) patients discontinued either drug due to AEs: 17 (32.7%) patients discontinued AXI, and 13 (25.0%) patients discontinued pembro with 10 (19.2%) discontinuing both drugs. Dose reduction of AXI due to AEs was reported in 16 (30.8%) patients. The most common AEs reported were diarrhea (84.6%), fatigue (80.8%), hypertension (53.8%), cough (48.1%), and dysphonia (48.1%). Increased alanine aminotransferase and aspartate aminotransferase occurred in 44.2% and 36.5% of patients, respectively. With this longer follow-up, there were no cumulative AEs or new AEs. OS by IMDC risk group will be presented. Conclusions: In patients with advanced RCC with almost 5 years of follow-up, the combination of AXI/pembro continues to demonstrate clinical benefit with no new safety signals. Clinical trial information: NCT02133742 .

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