Journal article
A Phase I Study of Alpha-1,3-Galactosyltransferase-Expressing Allogeneic Renal Cell Carcinoma Immunotherapy in Patients with Refractory Metastatic Renal Cell Carcinoma
The oncologist (Dayton, Ohio), Vol.25(2), pp.121-e213
02/2020
DOI: 10.1634/theoncologist.2019-0599
PMCID: PMC7011628
PMID: 32043778
Abstract
Lessons Learned
HyperAcute Renal immunotherapy was well tolerated and demonstrated antitumor activity in patients requiring salvage-line treatment for metastatic renal cell carcinoma (mRCC). HyperAcute Renal immunotherapy was safely administered with concomitant salvage-line treatments for mRCC, and it may be a candidate for inclusion in novel combinations for salvage treatment of mRCC because of its unique mechanism of action. Background HyperAcute Renal (HAR) immunotherapy exploits a naturally occurring barrier to xenotransplantation and zoonotic infections in humans to immunize patients against metastatic renal cell carcinoma (mRCC) cells. HAR consists of two allogeneic renal cancer cell lines genetically modified to express alpha(1,3)Gal, to which humans have an inherent pre-existing immunity. Methods Patients with refractory mRCC were eligible for this phase I dose-escalation trial. Concomitant treatment was permitted after the initial 2 months of HAR monotherapy. HAR was injected intradermally weekly for 4 weeks then biweekly for 20 weeks, totaling 14 immunizations. The primary endpoint was safety and determination of a maximum tolerated dose (MTD). Results Among 18 patients enrolled, two grade 3 adverse events (AEs) were attributed to HAR, lymphopenia and injection site reaction, and no grade 4/5 AEs occurred. The recommended phase II dose (RP2D) was 300 million cells. One patient had a partial response and eight patients had stable disease, for a disease control rate of 50% (9/18). Median overall survival with low-dose HAR was 14.2 months and was 25.3 months with high-dose HAR. Conclusion In pretreated mRCC, HAR immunotherapy was well tolerated and demonstrated antitumor activity. HAR immunotherapy may be a candidate for inclusion in novel combinations for salvage treatment of mRCC.
Details
- Title: Subtitle
- A Phase I Study of Alpha-1,3-Galactosyltransferase-Expressing Allogeneic Renal Cell Carcinoma Immunotherapy in Patients with Refractory Metastatic Renal Cell Carcinoma
- Creators
- Andrew W. Hahn - Huntsman Cancer InstituteCharles Drake - Columbia UniversitySamuel R. Denmeade - Sidney Kimmel Comprehensive Cancer CenterYousef Zakharia - University of IowaBenjamin L. Maughan - University of UtahEugene Kennedy - NewLink GeneticsCharles Link - NewLink GeneticsNicholas Vahanian - NewLink GeneticsHans Hammers - The University of Texas Southwestern Medical CenterNeeraj Agarwal - University of Utah
- Resource Type
- Journal article
- Publication Details
- The oncologist (Dayton, Ohio), Vol.25(2), pp.121-e213
- Publisher
- Wiley
- DOI
- 10.1634/theoncologist.2019-0599
- PMID
- 32043778
- PMCID
- PMC7011628
- ISSN
- 1083-7159
- eISSN
- 1549-490X
- Number of pages
- 7
- Language
- English
- Date published
- 02/2020
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984548263602771
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