If clinicians were looking for a signal to identify future directions and potential destinations in kidney cancer care and research, they might orient themselves with highlights from this year’s ASCO GU meeting. There was an abundance of new data, not much shattering, but noteworthy and intriguing, possibly setting the stage for inflection points yet to emerge.
(Editor’s note: All abstracts from the meeting can be viewed at this website: http://meetinglibrary.asco.org/abstractbysubcategory/2017%20Genitourinary
One of the big stories to emerge from the 2017 GU ASCO Scientific Sessions in Orlando, aside from an exciting agenda packed with a broad spectrum of findings, was the size of the meeting itself. From its relatively modest origins 10 years ago, this meeting has mushroomed exponentially. Attendance has soared from that first event when 1,450 attendees came to the venue to this year’s 3,300. That first meeting was described as small, accessible, and comfortable, allowing for “a more intimate setting for the practicing oncologist,” according to one account on ASCO’s website. With several thousand in attendance, that description may be debatable as the GU sessions become one of the major oncologic meetings worldwide.
Although it lacks the panache and attention given to the annual ASCO meeting in June, the GU sessions offer a striking opportunity for clinicians to catch up on specific trends in renal cell carcinoma (RCC) likely to evolve over the next few years, trends that could foreshadow results that may be presented at ASCO’s flagship meeting in Chicago. Among the standout abstracts and presentations from the 2017 sessions were:
- Intermediate-term outcomes from the DISSRM registry: a prospective analysis of active surveillance in patients with small renal masses. (Abstract 430, Ridwan A, et al.)
- A phase 2 study of atezolizumab with or without bevacizumab versus sunitinib in untreated metastatic RCC patients. (Abstract 431, McDermott DF, et al.)
- Evolution of circulating tumor DNA profile from first-line to second-line therapy in metastatic RCC. (Abstract 434, Pal SK et al.)
- Outcomes of PD-1/PD-L1 responders who discontinue therapy for immune-related adverse events (ir-AEs) results of a cohort of patients with metastatic RCC. (Abstract 467, McKay RR et al.)
- Pembrolizumab plus low-dose ipilimumab for patients with advanced RCC: Phase 1 KEYNOTE-029 study. Abstract 510, Choueiri TK, et al.)
• Intermediate-term outcomes from the DISSRM Registry (Abstract 430).
The goal of active surveillance as an alternative to primary intervention is to reduce the overtreatment of small renal masses, defined as solid renal masses ≤4.0 cm (clinical stage T1a). Since 2009, the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry prospectively enrolled 615 patients with small renal masses who chose to undergo primary intervention or active surveillance. Intervention was recommended to patients for masses with a rapid growth rate (0.5 cm/year) or increased tumor diameter (>4.0 cm). Primary outcomes were cancer-specific survival and overall survival; secondary outcomes included progression-free survival. Progression was strictly defined as a growth rate of 0.5 cm/year, greatest tumor diameter over 4.0 cm, new onset metastatic disease, or elective crossover.
Of the 615 enrolled patients, 298 (48.5%) chose primary intervention and 317 (51.5%) chose active surveillance. From the active surveillance cohort, 45 (14.2%) patients underwent delayed intervention. Median follow-up time for the entire registry was 2.9 years, with 203 (33.0%) patients followed for 5 years or more.
Ridwan et al found no difference in cancer-specific survival at 7 years between primary intervention and active surveillance (99.0% vs. 100%, respectively, P = 0.3). However, overall survival was higher in patients with primary intervention when compared to active surveillance at 5 years (93.0% vs. 80.2%, respectively) and 7 years (91.7% vs. 65.9%, respectively, P = 0.002). The 5-year and 7-year progression free survival rate in the active surveillance cohort was 76.7% and 48.4%, respectively.
This study helps clarify the extent to which active surveillance may be an effective strategy in the intermediate term for patients with small renal masses. In the intermediate term, active surveillance appears to be as effective as primary intervention from a cancer-specific survival for carefully selected patients with small renal masses. As cancer-specific survival appears to be similar in the intermediate term, the overall survival difference can be attributed to selection bias and patient comorbidities. As the registry matures, further studies will elucidate the outcomes of active surveillance in the long term. Clinical trial information can be found at NCT02346435.
• A novel immunotherapy combination
(atezolizumab + bevacizumab) vs sunitinib (Abstract 431).
One of the major obstacles to overcome with the use of VEGF-directed therapy is the resistance that invariably develops, often within the first year. With more attention focused on the use of immune checkpoint blockade there is keen interest in whether anti PD-L1 therapy can improve efficacy while still achieving an acceptable safety profile. McDermott et al evaluated the safety of a novel combination of atezolizumab (anti-PD-L1) with bevacizumab (anti-VEGF); it was compared with atezolizumab monotherapy and with sunitinib (TKI) in first-line mRCC.
Treatment-naive mRCC patients were randomized to one of 3 arms: atezolizumab 1200 mg IV q3w + bevacizumab 15 mg/kg IV q3w, atezolizumab alone, or sunitinib 50 mg PO daily 4 weeks on/2 weeks off. Crossover to the combination arm after disease progression was allowed for patients receiving atezolizumab alone or sunitinib. Median follow up was 20.7 months. The PFS HR in ITT pts was 1.00 for atezolizumab + bevacizumab vs sunitinib and 1.19 for atezolizumab vs sunitinib. In PD-L1+ patients, the PFS HR was 0.64 for atezolizumab + bevacizumab vs sunitinib and 1.03 for atezolizumab vs sunitinib. Treatment-related Grade 3-4 adverse events (AEs) were seen in 40%, 16% and 57% of patients in the atezolizumab + bevacizumab, atezolizumab, and sunitinib arms, respectively. AEs leading to death occurred in 3%, 2% and 2% of pts, respectively.
This is a phase 2 study and the phase 3 results of the novel combination are eagerly awaited. Atezolizumab + bevacizumab resulted in encouraging antitumor activity in the PD-L1+ subgroup of first-line RCC patients. Furthermore, the safety profile of atezolizumab + bevacizumab is consistent with the known profile of each drug when considered separately, although the high rate (40%) of grade 3-4 AEs is not insignificant. In PD-L1 positive patients there was favorable efficacy data. The clinical benefit of atezolizumab + bevacizumab vs sunitinib will be evaluated in the ongoing Phase 3 study IMmotion151 (NCT02420821). Clinical trial information on the ASCO GU data can be found at NCT01984242.
• Are there potential implications with the evolution of circulating
tumor DNA (ctDNA) profile from first-line to second-line therapy
in metastatic renal cell carcinoma (mRCC)? (Abstract 434)
Pal et al examined circulating tumor DNA (ctDNA) from patients undergoing first-line and second-line therapy. The authors studied whether these changes could ultimately impact therapeutic choices. Treatment of mRCC typically involves mechanistically distinct agents across the first and second line settings. ctDNA provides a promising platform to conveniently investigate temporal changes in overall genomic profiles of patients undergoing systemic therapy.
Data were obtained from patients with mRCC who underwent ctDNA profiling as a part of routine clinical care at progression using a CLIA-certified platform evaluating 70 genes. Genomic alterations (GAs) were pooled for the entire cohort. A comparison of first line (1L) vs. second line (2L) setting was performed, with grouping based on conventional practice patterns (1L regimens included sunitinib, pazopanib and bevacizumab, and 2L regimens included everolimus, axitinib, cabozantinib, and nivolumab). ctDNA results from 224 pts with mRCC were assessed (89 clear cell, 37 non-clear cell, 98 unknown). GAs were detected in 78.6% of patients. The most frequent GAs in the overall cohort included TP53 (35%), VHL (23%), EGFR (17%), NF1 (16%), and ARID1A (12%). 64 and 56 patients received 1L and 2L agents, respectively. The average number (range) of ctDNA alterations detected was 2.9 (1-14) in 1L and 3.7 (1-16) in 2L with median (range) ctDNA variant allele fractions of 0.23 (0.05-9.92) in 1L and 0.24 (0.04-47.14) in 2L. The highest disparity in GA frequencies in 2L vs. 1L were in TP53 (49% vs. 25%), VHL (29% vs. 25%), NF1 (20% vs. 15%), EGFR (17% vs. 21%), and PIK3CA (17% vs. 8%). Isolating 2L patients who specifically received 1L VEGF-therapy, these differences were even more prominent in comparison to 1L pts: TP53 (64% vs. 31%), PIK3CA (29% vs. 8%), and NF1 (29% vs. 4%).
This report is the largest assessment of ctDNA in mRCC to date; the majority of patients demonstrating clinically relevant GAs. Increasing p53 and mTOR pathway (e.g, NF1, PIK3CA) alterations in 2L patients who received 1L VEGF-directed therapy may help elucidate mechanisms of 1L therapy resistance. Increasing GA frequency from 1L to 2L patients may have implications for immunotherapeutic approaches. Interestingly, the rate of TP53 mutations in this cohort is surprisingly high. While ctDNA offers an easily accessible means to study genomic alterations, and a potential method to assimilate intratumoral heterogeneity, these results still need to be validated in additional patient cohorts, and using different ctDNA platforms.
• Immune-related adverse events/outcomes of PD-1/PD-L1
responders who discontinue therapy early. (Abstract 467)
Early findings from a new study appear to challenge the current standard practice for immune checkpoint inhibitor therapy—continuing treatment until cancer worsens. Among patients with advanced kidney cancer who stopped anti-PD-1/PD-L1 immunotherapy early due to adverse events, 42% had a durable response, meaning they were able to remain off additional systemic therapy for 6 months or more. More broadly, this insight may help alleviate some patients’ concerns about the impact of discontinuing immunotherapy. Although there have been prior anecdotal data hinting at this possibility, the authors note that this is the first study evaluating the outcomes of patients with metastatic renal cell carcinoma who stop anti-PD-1/PD-L1 therapy due to adverse events. While this is a small case series, with findings that need validation in a larger group of patients, it underscores that in some cases, immunotherapy can have lasting benefits—even beyond treatment discontinuation.
The analysis included 19 patients with mRCC that responded to immune checkpoint inhibitor therapy. The majority (63%) received anti-PD-1/PD-L1 therapy as a stand-alone treatment; 37% received anti-PD-1/PD-L1 inhibitors in combination with other systemic treatments. The median time on immunotherapy was 5.5 months. All 19 patients stopped immunotherapy early due to immune-related adverse effects.
In 4 patients, disease progression occurred immediately after the treatment was stopped, while 8 patients (42%) had a durable response and remained off any additional therapy for at least 6 months from the time of treatment discontinuation. While these findings are noteworthy and compelling, the study population was quite small. It would be interesting to study predictors of such a durable response to immunotherapy. Meanwhile, the researchers are developing a prospective clinical trial that will further explore the outcome of immunotherapy treatment discontinuation in patients without disease progression.
This study provides welcome news for patients who are unable to continue immunotherapy as a result of adverse effects. It is reassuring to see that some patients may continue to benefit from immunotherapy even if they need to discontinue it. More broadly, these findings call into question the current standard of continuous treatment with immunotherapy, though longer-term follow-up of patients is needed to identify patients in whom continuous dosing is not required, and evaluate long-term outcomes in this population.
• Combining pembrolizumab and low-dose ipilimumab:
the KEYNOTE-029 Study. (Abstract 510)
The anti-CTLA-4 antibody ipilimumab and anti-PD-1 antibody pembrolizumab have demonstrated efficacy in a range of patients with advanced malignancies. While these immune checkpoint inhibitors have shown activity as monotherapy, combination therapy has the potential to further improve outcomes. KEYNOTE-029 (NCT020 89685) is a phase 1/2 study designed to assess the safety and efficacy of this combination or pegylated interferon alfa-2b (IFN-a) in patients with advanced melanoma or RCC.
The authors have reported on the phase 1 portion of the study in patients with mRCC treated with pembrolizumab + ipilimumab. The study group included patients ≥18 years with advanced/unresectable or metastatic clear cell RCC who received at least one prior therapy for metastatic disease, had at least 1 measurable lesion per RECIST v1.1, and were ECOG PS 0-1. Patients received pembrolizumab 2 mg/kg q3w + low-dose ipilimumab (1 mg/kg q3w for 4 doses) until disease progression, unacceptable toxicity, investigator/patient decision, or 2 years of pembrolizumab treatment. AEs were monitored throughout treatment and for 30 days thereafter and graded per NCI CTCAE v4.0. Primary endpoint was safety; primary efficacy endpoint was ORR assessed per RECIST v1.1 by independent central review. At the time of presentation, 10 patients with RCC had received pembrolizumab + low-dose ipilimumab.
With a median follow-up of 17.4 months (0.9-23.5 months), 70% of patients experienced AEs of any grade, most commonly fatigue (30%); and 50% experienced grade 3-4 AEs, most commonly increased lipase (20%). 50% discontinued pembrolizumab because of AEs, most commonly increased lipase (40%). There were no treatment-related deaths. ORR was 20% (2 partial responses). An additional 3 patients had stable disease and the disease control rate was 50%. From this phase 1 study, Choueiri et al concluded that the combination of pembrolizumab + low-dose ipilimumab for 4 doses, followed by pembrolizumab monotherapy, demonstrates a manageable toxicity profile and preliminary antitumor activity in patients with advanced RCC. Clinical trial information: NCT02089685
• • • • • • •
A Very Brief ‘Take Home’: Summaries of Additional Selected Abstracts
from ASCO GU Cover a Broad Spectrum of New Findings
(Editor’s note: To access the full abstracts to these abbreviated summaries, please see the link cited in the beginning of this article.)
• Comparative effectiveness of tumor response assessment methods:
Standard-of-care versus computer-assisted response evaluation.
(Abstract 432) Brian C. Allen, et al. Duke University Medical Center, Durham, NC
Background: In clinical trials and clinical practice, tumor response assessment with computed tomography (CT) defines critical end points in patients with metastatic disease treated with systemic agents. Methods to reduce errors and improve efficiency in tumor response assessment could improve patient care.
Conclusion: Computer-assisted tumor response evaluation reduced errors and time of evaluation, indicating better overall effectiveness than manual tumor response evaluation methods that are the current standard-of-care.
• Cryoablation of cT1 renal masses in the “healthy” patient:
Early outcomes from Mayo Clinic. (Abstract 433). Harras B. Zaid, et al,
Mayo Clinic, Rochester, MN
Background: Current guidelines suggest that percutaneous thermal ablation (PTA) can be utilized in patients with significant comorbidity who are unable to tolerate surgery (radical or partial nephrectomy). However, the use of PTA in healthy patients, who are otherwise candidates for surgery, has been limited. A single-institutional experience was reviewed in healthy patients electing to undergo cryoablation.
Conclusion: In this cohort of “healthier” patients with cT1 solitary renal masses, cryoablation offered reasonable short-term oncologic control. While longer follow-up data are needed to evaluate for durability of effectiveness, cryoablation in healthy patients, particularly those with challenging surgical anatomy, warrants further study and longer follow-up.
• Changes in tumor burden and IMDC class after
active surveillance (AS) for metastatic renal cell carcinoma
(mRCC). (Abstract 435) Davide Bimbatti, et al, Medical Oncology,
Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
Background: Targeted therapies (TT) have improved survival in mRCC but treatment-related toxicities may worsen quality of life and lead to treatment discontinuation. AS is a feasible strategy in patients with indolent disease but effects on tumor burden (TB) and prognosis have not been investigated.
Conclusion: AS is an option for management of mRCC pts with good and intermediate prognosis. AS allows for delay in the start of TT, temporarily avoiding toxicity and worsening quality of life. Despite the fact patients on AS have increased TB but rarely a worsening of prognostic class, survival remains acceptable, and the effectiveness of subsequent therapy appears not to be affected.
• A single-arm biomarker-based phase II trial of savolitinib
in patients with advanced papillary renal cell cancer (PRCC).
(Abstract 436) Toni K. Choueiri, et al, Dana-Farber Cancer Institute,
Harvard Medical School, Boston, MA
Background: Savolitinib (HMPL504/Volitinib, AZD6094) is a potent, selective MET inhibitor. MET and its ligand, HGF, are known to play an important role in the molecular events underlying oncogenesis in PRCC, a disease without a clear effective standard of care and marked by alterations of MET in many patients. This study evaluated savolitinib in PRCC patients dosed at 600 mg daily until disease progression.
Conclusion: In this largest biomarker-profiled trial dedicated to PRCC, savolitinib was generally well tolerated with anti-tumor activity in MET-driven patients. These findings warrant further clinical investigation of savolitinib in MET-driven PRCC.
• Impact of obesity and adiponectin signaling in patients with
renal cell carcinoma: A potential mechanism for the obesity paradox.
(Abstract 449) Shintaro Narita, et al, Department of Urology, Akita University Graduate School of Medicine, Akita, Japan
Background: Obesity increases the risk of renal cell carcinoma (RCC); however, obese patients experience longer survival than non-obese patients. The mechanism of this “obesity paradox” is unknown. This paper examined the impact of obesity, total adiponectin (AD) level, and intratumoral AD receptors expression on RCC aggressiveness and survival, and also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells with exogenous adiponectin stimulation.
Conclusion: Low BMI and high AD level are associated with cancer aggressiveness and poor survival in RCC patients treated surgically. AD modulates proliferation and apoptosis, which may underlie the “obesity paradox” of RCC.
• Combined inhibition of autophagy with mTOR inhibitor to
enhance cell death in renal cell carcinoma. (Abstract 450)
Hua Chen, et al, University of Alberta, Edmonton, AB, Canada
Background: mTOR (mammalian target of rapamycin) and autophagy are increasingly recognized as being a central cellular and pathological process for numerous hu-man diseases, including renal cell carcinoma (RCC). Depending on the cellular context, autophagy may promote cancer cell survival or cell death. However, little is known about the mechanisms of regulating mTOR activity and autophagic function in RCC. The authors hypothesized that autophagy promotes cell survival via mTOR mediated-phosphatidylinositol 3-kinase (PI3K)/ AKT pathway and is regulated by the von Hippel-Lindau (VHL) tumor suppressor.
Conclusion: These results support mTOR and autophagy as potential targets of anticancer drugs and implicate VHL in the control of the autophagy in RCC. Furthermore, this work suggests that combined inhibition of autophagy and mTOR pathways could be a novel therapeutic strategy for the treatment of RCC.
• Effect of NKTR-214 on the number and activity of
CD8+ tumor infiltrating lymphocytes in patients with
advanced renal cell carcinoma. (Abstract 454) Michael E. Hurwitz,
Yale School of Medicine, New Haven, CT
Background: Patients with low baseline CD8+ T-cells within the tumor microenvironment (TILs) have a poor response to immune checkpoint inhibitors. Agents designed to specifically activate and expand CD8+ T cells may improve clinical outcomes in patients with low TILs. NKTR-214 is a CD-122-based agonist designed to provide sustained signaling through the heterodimeric IL-2 receptor pathway (IL-2Rbɣ) and preferentially activate and expand NK and effector CD8+ T cells over CD4+ T regulatory cells. A dose escalation, open-label, trial was initiated to assess the safety of NKTR-214 and explore immune changes in the blood and tumor microenvironment in patients with advanced solid tumors.
Conclusion: NKTR-214 increased immune infiltration in the tumor and increased anti-tumor activity in patients who previously progressed on TKIs, with a favorable safety profile. The ability to alter the immune environment and increase PD-1 expression on effectors T cells may improve the effectiveness of anti-PD-1 blockade. A trial combining NKTR-214 and nivolumab is underway.
• Meta-analysis of disease free survival (DFS) as a surrogate
for overallsurvival (OS) in localized renal cell carcinoma (RCC).
(Abstract 459) Lauren C. Harshman, et al, Dana-Farber Cancer Institute, Boston, MA
Background: OS is a critical endpoint for adjuvant RCC trials testing the benefit of early systemic therapy to increase cure rates, but requires long follow-up duration and significant resources. The potential use of DFS as a surrogate for OS when assessing the efficacy of adjuvant therapy in localized RCC was explored.
Conclusion: Across trials of adjuvant systemic therapy for localized RCC, this meta-analysis observed a moderate correlation between 5-year DFS and OS rates and between treatment effects (HRs) on these endpoints. Future meta-analyses of more mature trials in the era of modern adjuvant targeted therapy are needed to further evaluate the surrogacy of intermediate endpoints.
Further granularity may be achieved using individual patient data instead of aggregate data to assess different and earlier time points for surrogacy than are commonly reported.
• T cell infiltration in matched renal biopsy (bx) and nephrectomy (nx)
samples in renal cell carcinoma (RCC). (Abstract 472) Haris Zahoor, et al,
Cleveland Clinic, Cleveland, OH
Background: T-cell infiltration in tumors has been investigated as a biomarker of response to checkpoint inhibitors. There are no data regarding the association of T-cell infiltration in matched biopsy and nephrectomy samples without intervening treatment. Understanding this association could enable further study of this potential biomarker in future neoadjuvant studies. Matched biopsy and nephrectomy samples (without intervening systemic therapy) were identfied from patients with non-metastatic RCC.
Conclusion: The analysis found a modest correlation between the frequencies of CD8+ T cells between matched biopsy and nephrectomy samples (r= 0.39; p=0.03). CD3+ and CD4+T cells did not show significant correlation. The authors concluded that biopsy material could be potentially used to accurately assess the degree of CD8+T cell infiltration in RCC.
• Cabozantinib for the treatment of patients with metastatic
varianthistology renal cell carcinoma (vhRCC): A retrospective study.
(Abstract 478) Matthew T. Campbell, et al, The University of Texas
MD Anderson Cancer Center, Houston, TX
Background: Cabozantinib (C) prolongs overall survival (OS) and progression-free survival (PFS) in patients with metastatic clear-cell renal cell carcinoma (ccRCC) that progressed on first-line VEGFR-TKI. No standard of care systemic therapy exists for the management of patients with metastatic vhRCC.
Conclusion: In this retrospective study, cabozantinib produced a clinically meaningful benefit in patients with metastatic variant histology RCC, the majority of whom had progressive disease on prior VEGFR-TKIs. Prospective trials of cabozantinib in vhRCC are warranted.
• Clinical activity of PD1/PDL1 inhibitors in metastatic
non-clear cell renal cell carcinoma (nccRCC). (Abstract 482)
Raphael Brandao Moreira, et al, Dana-Farber Cancer Institute, Boston, MA
Background: PD1/PDL1 inhibitors have shown significant activity in the treatment of patients with metastatic clear cell renal cell carcinoma (ccRCC), but their activity in nccRCC is poorly characterized.
Conclusion: PD1/PDL1 blockade resulted in some activity in patients with various nccRCC histologies. However, prior to routine use of PD-1/PD-L1 blocking agents in nccRCC, prospective trials are necessary.
• Tumor genomic analysis for 128 renal cell carcinoma (RCC)
patients receiving first-line everolimus: (Abstract 484) Correlation
between outcome and mutations status in MTOR, TSC1, and TSC2.
Martin Voss, et al, Memorial Sloan Kettering Cancer Center, New York, NY
Background: mTOR inhibitors are approved for the management of metastatic RCC. Prior studies have suggested that somatic mutations in mTOR, TSC1, and TSC2 may sensitize tumors to everolimus. This hypothesis was tested through next generation sequencing (NGS) of tumors from a large cohort of patients treated with everolimus in the randomized RECORD3 trial of first-line everolimus vs. sunitinib.
Conclusion: “One-dimensional” mutation status for core components of the mTOR signaling pathway did not correlate with PFS in this dataset. Grouping based on more detailed characterization incorporating copy number status and functional annotation may provide better insights and should be considered for future biomarker development.
• Impact of cytoreductive nephrectomy on timing of systemic
therapy in metastatic kidney cancer. (Abstract 503) Liam Connor Macleod, et al, University of Washington, Seattle, WA
Background: High rates of disease control with systemic therapy in the post-cytokine era for metastatic renal cell carcinoma (mRCC) cause apprehension that cytoreductive nephrectomy (CN) may delay effective systemic therapy. This study evaluated factors associated with early mortality and time to systemic therapy after CN.
Conclusion: These data suggest that markers of frailty, progressive disease, and surgical morbidity may contribute to surgical-related deaths or hinder patients receiving potentially disease-controlling therapy when treated with initial CN in mRCC. Going forward, existing surgical prognostic models could incorporate risk factors for surgical-related morbidity/mortality and risk factors for delay in initiating postoperative systemic therapy when considering CN.
• A phase 1 study of alpha-1,3-galactosyltransferase-expressing
allogeneic renal cell carcinoma immunotherapy in patients with
metastatic renal cell cancer. Hans J. Hammers, et al, The University of Texas Southwestern Medical Center, Dallas, TX
Background: HyperAcute Renal (HAR) immunotherapy consists of two allogeneic renal cancer cell lines that have been genetically modified to express the carbohydrate a(1,3)Gal, to which humans have an inherent pre-existing immunity. HAR is designed to leverage this mechanism to educate the immune system towards antigens expressed by the patient’s own tumor cells.
Conclusion: RCC is considered an immunogenic tumor based on its response rate to immune checkpoint blockade and IL-2, occasional spontaneous regression, and the high level of tumor T cell infiltration. HAR was well tolerated in this patient population. Therefore, RCC is an appropriate tumor type to target with combination immunotherapy including HAR. KCJ