Ashling Wahner

Researchers are exploring the use of CAR T-cell therapy in clear cell renal cell carcinoma, a type of kidney cancer: © stock.adobe.com.

Researchers are building on the success of CAR T-cell therapy in blood cancers to explore its use in clear cell renal cell carcinoma, a type of kidney cancer. According to Dr. Wayne A. Marasco, this work has led to the development of a dual-targeting CAR T-cell treatment for advanced disease in patients whose tumors overexpress CAIX and CD70.

, Marasco highlighted the goal of evaluating a dual-targeted, fine-tuned, and immune-restoring CAR T-cell therapy for the treatment of patients with CAIX- and CD70-overexpressing clear cell renal cell carcinoma. He noted that this therapeutic strategy, pending clinical investigation, may be a path toward curing this disease subtype.

Marasco is a professor of Medicine at Brigham and Women’s Hospital and a principal investigator of Cancer Immunology and Virology at Dana-Farber Cancer Institute in Boston, Massachusetts.

Following the established role of CAR T-cell therapy for the management of hematologic malignancies, recent work has investigated the CAR T-cell therapy approach in solid tumors, Marasco explained. For example, the phase 1 COBALT-RCC trial evaluated Yescarta, a novel CD70-targeting CAR T-cell therapy, for the treatment of patients with advanced or refractory clear cell renal cell carcinoma.

Dose-limiting toxicities were not observed, and the disease control rate was 81%, with 1 patient remaining in durable complete response at 3 years. The study included 16 patients at least 18 years of age who weighed at least 42 kg with unresectable or metastatic renal cell carcinoma that had relapsed on or was refractory to standard of care. Patients on the trial were also required to have a Karnofsky performance status of at least 80% and adequate renal, liver, cardiac and pulmonary organ function.

The phase 1 TRAVERSE trial evaluated the allogeneic CAR-T ALLO-316 for the treatment of patients with advanced or metastatic clear cell renal cell carcinoma following lymphodepletion comprising fludarabine and cyclophosphamide with or without ALLO-647. Early data from the study demonstrated that among 44 patients, the overall response rate was 20% in patients treated with the lymphodepletion regimen (6 patients) who had CD70-positive tumors. Treatment-emergent side effects occurred in 96% of patients, with grade 3 or higher side effects observed in 84% of patients. Patients included on the study were at least 18 years of age with advanced clear cell renal cell carcinoma, an ECOG performance status of 0 or 1 and disease progression following immune checkpoint inhibition and VEGF-targeted therapy.

The dual-targeting aspect of the CAIX/CD70-directed CAR T-cell product aims to improve efficacy, whereas the fine-tuned aspect aims to improve safety by targeting only high-density antigen expressed on the tumor cells without targeting low-density antigen on healthy tissues. Moreover, the immune-restoring aspect changes the tumor microenvironment by locally secreting checkpoint blockade inhibitors to restore antitumor immunity.

Preclinical Efficacy and Safety of CAR T-Cell Therapy in Clear Cell Renal Cell Carcinoma

Early efficacy data from a preclinical study demonstrated that CD70 is not universally expressed on renal cell carcinoma cells, and therefore, some targets were CD70-negative, Marasco explained.

“[However,] all tumors express CAIX, which is still the molecule that is most desirable. The killing data in the immunofluorescence analysis show the specificity of the dual-targeted CAR T-cell therapy for both targets. In humanized animal studies, the CAR T-cell therapy effectively cured the animals from the tumors, and in these animals, we don’t even see the tumors after the therapy,” he said.

Although preliminary efficacy data have shown promise, safety data have been the most significant concern, notably due to CAIX overexpression, Marasco added.

“We spent over a decade working this out to be able to develop high-avidity, low-affinity antibodies as the targeting moiety. Why would you want that? Well, we certainly don’t want to target CAIX if it’s in limited quantities, because a high-affinity targeting residue will bind to it,” he said. “You want only targeting molecules that are recognized with high density, and that’s what we engineered.”

Most notably, the immune-restoring aspect of this therapy is “the most important part of this change in the tumor microenvironment,” according to Marasco.

“If we administer CAR T-cell therapy without delivering a payload to the tumor site, we do not ever cure the animals of tumors,” Marasco emphasized. “If we deliver monoclonal antibodies at the tumor sites, which is what we’re doing, we secrete antibodies and checkpoint blockade inhibitors locally at the tumor site, and we can get complete cures.”

Future Steps for Examining CAR T-Cell Therapy in

The investigational dual-targeted CAR T-cell therapy in development by Marasco and colleagues targets CAIX and CD70 and delivers an anti–PD-1 and -CTLA4 bispecific antibody at the tumor site, Marasco reported. Currently, ongoing preclinical studies with this product are nearing finishing stages, which will guide the next step of GMP manufacturing and subsequently submitting an investigational new drug application to the FDA, he explained.

“We’re on schedule to be able to complete this preclinical research and file an investigational new drug application sometime, hopefully in September or October 2025,” Marasco concluded.

“Redesigning CAR T cells for solid tumors: a new path toward cures of ccRCC,” by Dr. Wayne A. Marasco. Presented at: 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA.

“CD70-targeted allogeneic CAR T-cell therapy for advanced clear cell renal cell carcinoma,” by Dr. Sumanta K Pal. 

A safety and efficacy study evaluating CTX130 in subjects with relapsed or refractory renal cell carcinoma (COBALT-RCC). ClinicalTrials.gov. Updated January 8, 2025. Accessed July 17, 2025.

“ALLO-316 in advanced clear cell renal cell carcinoma (ccRCC): updated results from the phase 1 TRAVERSE study,” by Dr. Samer A. Srour. 

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Articles

Researchers are advancing CAR T-cell therapy from blood cancers to clear cell renal cell carcinoma, focusing on dual-targeting CAIX and CD70. This approach aims to enhance efficacy and safety by fine-tuning antigen targeting and restoring antitumor immunity. Early trials, such as COBALT-RCC and TRAVERSE, show promising disease control rates and manageable toxicities. Preclinical studies highlight the potential of dual-targeted CAR T-cells to cure tumors in animal models. Ongoing research is progressing towards clinical trials, with an investigational new drug application anticipated by late 2025.

Researchers are building on the success of CAR T therapy in blood cancers to explore its use in clear cell renal cell carcinoma, a type of kidney cancer.

Dual-Targeting CAR T Therapy Shows Potential in Advanced Kidney Cancer  

Early data suggest personalized neoantigen vaccines activate the immune system and sustain tumor control in some patients with kidney cancer.

Early data show personalized neoantigen vaccines can activate the immune system and produce lasting tumor control in some patients with kidney cancer, setting the stage for more studies in the adjuvant setting, said Dr. David A. Braun.

, Braun described the rationale and design of a phase 1 trial investigating the efficacy of personalized neoantigen vaccines in patients with high-risk, resectable clear cell renal cell carcinoma (ccRCC); key antitumor strengths of this vaccine; and why the minimal residual disease (MRD) setting may be most optimal for developing therapeutic vaccines for patients with kidney cancer and other diseases with relatively low mutational burdens.

Braun is an assistant professor of medicine (medical oncology) and the Louis Goodman and Alfred Gilman Yale Scholar at the Yale School of Medicine, and a member of the Center of Molecular and Cellular Oncology at Yale Cancer Center in New Haven, Connecticut.

Spotlighting the Promise of Neoantigen Vaccines in RCC

Braun framed his presentation with a glance at the mechanisms of antitumor immunity in kidney cancer. He used the analogy of a car, explaining that the goal of cancer therapy is to drive CD8-positive T cells toward the tumor as quickly and accurately as possible. He noted that historically, this goal has been achieved through immune activation strategies, such as immune checkpoint inhibitors, which he likened to releasing the brakes of the car, as well as novel cytokine and immune agonists, which are comparable to pressing the gas pedals. However, he emphasized that propelling the next generation of kidney cancer therapies will rely on immune navigation approaches, such as antigen-directed therapies, which steer the immune system in the optimal direction.

“Personalized cancer vaccines are an ideal example of how to do that,” Braun stated.

Braun and colleagues saw the potential for neoantigens as effective targets for antitumor immunity and T-cell response based on the previously reported performance of neoantigen-directed treatment approaches across tumor types, including melanoma, pancreatic cancer, and glioblastoma. However, Braun explained that neoantigen-targeting treatment presents a heightened challenge in kidney cancer, which, although immunogenic, has a modest mutation burden and therefore a lower number of targetable neoantigens. Nevertheless, acknowledging the dearth of effective RCC therapies in the adjuvant setting, Braun and colleagues aimed to design a personalized vaccine that could target the neoantigens present in kidney cancer.

This small study enrolled 9 patients with high-risk, resectable (stage 3 or 4) ccRCC who had undergone complete tumor resection. The investigators created personalized vaccines for these patients through tumor sequencing and neoantigen prediction. These vaccines were composed of synthetic long peptides that contained up to 20 personal neoantigens present in each tumor. These peptides were divided into four pools to decrease competition with local lymph nodes in the event of certain epitopes presenting as immunodominant, Braun stated in a question-and-answer session following his presentation.

Regarding the later-stage patient population, when asked how neoantigen-directed vaccines might perform in earlier-stage tumors, Braun explained, “The immune composition is different in those early-stage tumors, so I don’t think we’ll know until we try. At the same time, some of those earlier-stage tumors tend to have excellent outcomes, so it’s not that [these vaccines] would be for every early-stage tumor, but if we can identify ones that are higher risk, those will be the ones to think about how to target.”

In another answer, he noted that the most convincing levels of success with cancer vaccines have been shown in settings of MRD, such as the adjuvant setting in kidney cancer. Therefore, he expressed that although the vaccines currently in development may not be advanced enough to elicit meaningful responses in the metastatic setting — at least when used alone — he and co-investigators hypothesized that this type of therapy would be most effective in patients with minimal, manageable disease that is nevertheless at high risk of recurrence. 

Outlining the Trial Design and Feasibility Analysis

The vaccines were administered with or without Yervoy (ipilimumab) in 2 phases: a priming phase to activate and prime the T cells, followed by a boost phase to facilitate long-lasting T-cell memory.

Regarding the feasibility of manufacturing a neoantigen-directed vaccine for a disease with a low mutational burden, the investigators found that despite the low prevalence of coding mutations in the patient population, they could create a multi-epitope vaccine directed at single nucleotide variants and frameshift insertion deletions that corresponded with kidney cancer driver mutations.

Highlighting the Durable Efficacy of Personalized RCC Vaccines

From there, Braun explained that the second goal of the study was to determine the immunological efficacy of these vaccines.

“The basic question was: Are the T cells reacting to these neoantigens and capable of recognition?” He asked.

Prior to vaccination, most patients had barely detectable or undetectable levels of neoantigen immunity. However, after vaccination, neoantigen-specific responses were observed in the peripheral T cells of all treated patients. For instance, at baseline, one patient had no detectable immunity for three of the four vaccine peptide pools. However, during the vaccination period, this patient exhibited strong peripheral T-cell responses.

When analyzing which neoantigens were associated with responses, Braun reported that, surprisingly, these results were not random. Instead, the investigators saw the most effective immune responses against known kidney cancer driver mutations, such as those in PIK3CA, PBRM1, KDM5C, BAP1 and VHL.

To determine the durability of these responses, the investigators tracked levels of vaccine-specific T-cell clones in the peripheral blood. At baseline, these levels were undetectable or near the lower limit of detection. However, upon vaccination, these levels rose rapidly, persisting through the boost phase. Additionally, Braun spotlighted that in some patients, vaccine-reactive T-cell clones were still observed months to years after vaccination, indicating the durable T-cell immunity elicited by this treatment.

Furthermore, the investigators conducted an in vitro assessment of the antitumor activity of these vaccines by placing vaccine-expanded T cells back on top of the corresponding patients’ tumors. In total, seven of the nine patients had generated detectable levels of vaccine-specific T cells that reacted against the autologous whole-tumor cells.

Overall, at a median follow-up of 40.2 months from the time of surgery, none of the enrolled patients had a recurrence of RCC. Moreover, no dose-limiting toxicities were reported.

“We’re encouraged by the fact that all nine patients, despite having high-risk disease, remained free of kidney cancer throughout the study,” he emphasized, noting that one patient died of unrelated causes during the study.

Acknowledging How the Study’s Limitations Give Way to Further Research

Braun noted that the small sample size is a key limitation of this research that warrants follow-up studies to determine the clinical relevance of these findings.

“These neoantigen vaccines are feasible for kidney cancer,” Braun concluded. “They can elicit effective T-cell responses and antitumor activity. At least this preliminary signal of clinical activity sets up [the phase 2] INterpath-004, the next study that will hopefully demonstrate some clinical activity.”

Notably, the phase 2 INterpath-004 trial is investigating adjuvant treatment with the mRNA-based personalized cancer vaccine intismeran autogene (V940) plus Keytruda (pembrolizumab) versus placebo plus Keytruda in patients with RCC.

“Personalized vaccines in kidney cancer: a journey from concept to clinic” by Dr. Daniel A. Braun, et al., presented at the 2025 Kidney Cancer Research Summit.

“A neoantigen vaccine generates antitumour immunity in renal cell carcinoma” by Dr. Daniel A. Braun, et al., 

For more news on cancer updates, research and education, don’t forget to 

Early data suggest that personalized neoantigen vaccines can activate the immune system and provide lasting tumor control in some kidney cancer patients. A phase 1 trial investigated the efficacy of these vaccines in high-risk, resectable clear cell renal cell carcinoma (ccRCC). The study enrolled nine patients, creating personalized vaccines through tumor sequencing and neoantigen prediction. Results showed neoantigen-specific T-cell responses and durable immunity, with no RCC recurrence at a median follow-up of 40.2 months. The study's limitations highlight the need for further research, including the phase 2 INterpath-004 trial.

Personalized Neoantigen Vaccines Show Lasting Tumor Control in Kidney Cancer

The combination of first-line Bavencio and Inlyta was effective and safe in advanced RCC; stock.adobe.com

For patients with advanced renal cell carcinoma (RCC), first-line Bavencio (avelumab) in combination with Inlyta (axitinib) was effective and safe in a real-world population and delivered results consistent with those previously reported in clinical trials, according to findings from the primary analysis of the AVION study, which were presented at the 

At a data cutoff date of July 5, 2024, among patients with advanced RCC in Belgium, Germany, Greece, and Russia enrolled in the trial who received the combination in routine clinical practice (104 patients), the median overall survival (OS) was not reached (NR), the six-month OS rate was 89.1%, and the 12-month OS rate was 82.7%.

“Overall, results from AVION demonstrate the effectiveness, safety, favorable tolerability and stable health-related quality of life [HRQOL] of [Bavencio plus Inlyta] in a heterogeneous real-world population,” lead study author Dr. Axel Stuart Merseburger, and coauthors wrote in a poster of the data.

Palmar-plantar erythrodysesthesia syndrome: a condition with redness and pain on the palms and soles, often from cancer treatment.

Hypertensive crisis: a severe spike in blood pressure, typically over 180/120 mm Hg, risking organ damage.

Complete response (CR): no evidence of cancer after treatment.

Partial response: a significant reduction in tumor size, but not complete elimination.

Stable disease: cancer that hasn't worsened or shrunk significantly.

Progressive disease (PD): cancer that is growing or spreading despite treatment.

Overall survival (OS) rate: the percentage of patients alive after a certain time post-treatment.

Duration of OS: the time from diagnosis/treatment to death or end of study.

Progression-free survival (PFS): the time a patient lives without cancer worsening.

Overall response rate (ORR): the percentage of patients whose cancer shrinks or disappears.

Duration of response (DOR): the time cancer remains controlled after treatment.

Disease control rate (DCR): the percentage of patients with CR, partial response, or stable disease.

Stable health-related quality of life (HRQOL): maintaining a stable quality of life despite disease presence.

Dysphonia: voice changes due to cancer or treatment effects on the vocal cords.

Pruritus: itching, often caused by cancer treatments or malignancy.

ECOG performance status of 0/1 or 2: level of functioning, where 0 indicates no symptoms, 1 means mild symptoms and 2 indicates moderate symptoms limiting some activities.

Merseburger is chairman of the Clinic of Urology at University Hospital Schleswig-Holstein in Lübeck, Germany.

Any-grade side effects (AEs) were observed in 83.7% of patients, and grade 3 (severe) or worse AEs were observed in 34.6% of patients. AEs led to discontinuation of Bavencio or Inlyta in 9.6% and 14.4% of patients, respectively.

Any-grade treatment-related AEs (TRAEs) were reported in 67.3% of patients, and grade 3 or worse TRAEs were reported in 20.2% of patients. TRAEs led to discontinuation of Bavencio or Inlyta in 6.7% and 9.6% of patients, respectively.

The most common TRAEs were diarrhea (any-grade, 26%; grade 3 or worse, 4.8%), fatigue (13.5%; 1.9%), hypertension (10.6%; 1%), hypothyroidism (8.7%; 0%), dysphonia (8.7%; 0%), nausea (7.7%; 0%), palmar-plantar erythrodysesthesia syndrome (7.7%; 0%), pruritus (6.7%; 0%), decreased weight (5.8%; 0%), dyspnea (3.8%; 1.9%) and hypertensive crisis (2.9%; 1.9%).

Serious AEs and serious TRAEs were noted in 36.5% and 14.4% of patients, respectively. A total of 10.6% of patients received corticosteroids, immunosuppressants or hormonal therapy to manage any-grade TRAEs.

AEs led to death in four patients, and TRAEs led to death in one patient.

Previously, the phase 3 JAVELIN Renal 101 trial showed that first-line Bavencio plus Inlyta generated significantly longer progression-free survival (PFS), and higher objective response rates (ORRs) compared with Sutent (sunitinib) and had an acceptable, long-term safety profile in patients with advanced RCC. The final analysis of JAVELIN Renal 101 showed that in the overall population, at a minimum follow-up of 68 months, the median PFS was 13.9 months with the combination versus 8.5 months with Sutent. The ORRs in these respective arms were 59.7% and 32%.

Additionally, outcomes from the final OS analysis in the overall population favored the combination arm, although the OS difference between the two arms was not statistically significant. The median OS was 44.8 months with the combination versus 38.9 months with Sutent.

The findings from JAVELIN Renal 101 supported the 2019 FDA approval of Bavencio plus Inlyta for the first-line treatment of patients with advanced RCC. In 2019, the European Commission also approved the combination for this indication.

Despite these data and approvals, the AVION investigators noted that real-world data with the combination in clinical practice are limited.

The prospective, noninterventional AVION study enrolled patients being treated for locally advanced, recurrent or metastatic RCC in Belgium, Germany, Greece, and Russia who had already received one or two doses of frontline Bavencio plus Inlyta; these patients received further treatment with the combination during AVION. Patients needed to be at least 18 years of age, have histologically confirmed disease with any histological origin, and have an ECOG performance status of 0 to 2.

Patients received Bavencio intravenously at 800 milligrams (mg) every two weeks and Inlyta orally at 5 mg twice daily.

The primary end goal was the OS rate at 12 months from the date of the first treatment received after informed consent. Secondary end points included the 24-month OS rate, duration of OS, PFS, ORR, duration of response (DOR), disease control rate (DCR), safety and HRQOL.

In total, 105 patients were enrolled. One patient did not report Inlyta treatment prior to informed consent and was excluded from the analysis population.

Patients had a median age of 70 years; 34.6%, 40.4% and 25% of patients were younger than 65 years of age, between 65 and 75 years of age and older than 75 years of age, respectively. Most were male (70.2%). Additionally, 89.4%, 3.8% and 6.7% of patients had clear cell, sarcomatoid and other disease histology, respectively. PD-L1 status was negative, positive, not applicable and missing in 16.3%, 5.8%, 28.8% and 49% of patients, respectively. Prior anticancer treatments included adjuvant drug treatment (3.8%), surgery (75%), nephrectomy (66.3%) and radiotherapy (8.7%). At baseline, the median time since initial diagnosis was 0.7 years.

At the last follow-up, 20% of patients were still receiving Bavencio or Inlyta, 20% of patients had discontinued treatment and remained in follow-up, and 60% of patients had discontinued from the study. Reasons for study discontinuation included death (38.1%), completion of the study (28.6%), and loss to follow-up (15.9%).

The median duration of Bavencio treatment was 341 days, and the median duration of Inlyta treatment was 354 days. The median time to discontinuation of both Inlyta and Bavencio was 208 days.

Subgroup analyses of 12-month OS rates showed that among patients younger than 65 years of age, 65 to 75 years of age, and older than 75 years of age, the 12-month OS rates were 85.5%, 84.5% and 75.8%, respectively. Among patients with an ECOG performance status of 0/1 or 2, these rates were 84.3% and 57.1%, respectively. Among patients from Belgium, Germany, Greece and Russia, these respective rates were 87.5%, 86.2%, 71.9% and 95.2%.

Among patients with IMDC favorable-, intermediate-, and poor-risk disease, the 12-month OS rates were 92.6%, 74.1% and 82.5%, respectively. Among patients with clear cell, sarcomatoid, and other histologies, these respective rates were 83.1%, 100% and 66.7%. Patients who had undergone prior nephrectomy (69 patients) had a 12-month OS rate of 86.7% versus 73.4% among those who had not undergone prior nephrectomy (35 patients).

In the overall population, the median PFS was 11.3 months. The six- and 12-month PFS rates were 72.5% and 48.4%, respectively.

Among 87 response-evaluable patients, the ORR was 46%, including complete response (CR), partial response, stable disease, progressive disease (PD), and non-CR/non-PD rates of 4.6%, 41.4%, 31%, 20.7% and 2.3%, respectively. The DCR was 79.3% and the median DOR was NR.

“Real-world effectiveness and safety of first-line (1L) avelumab + axitinib in patients with advanced renal cell carcinoma (aRCC): primary analysis of the AVION study.” by Dr. Merseburger A, et al., 

“Avelumab + axitinib versus sunitinib in patients (pts) with advanced renal cell carcinoma (aRCC): final overall survival (OS) analysis from the JAVELIN Renal 101 phase 3 trial.” by Dr. Motzer RJ, et al., 

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The combination of Bavencio (avelumab) and Inlyta (axitinib) has shown effectiveness and safety in treating advanced renal cell carcinoma (RCC) in a real-world setting, consistent with previous clinical trials. The AVION study reported a six-month overall survival (OS) rate of 89.1% and a 12-month OS rate of 82.7%. Adverse events (AEs) were common, with 83.7% experiencing any-grade AEs and 34.6% experiencing severe AEs. The study highlighted the combination's favorable tolerability and stable health-related quality of life (HRQOL) in a diverse patient population.

In a real-world analysis of patients with advanced RCC, the combination of first-line Bavencio and Inlyta was effective and safe.

Real-World Data Confirms Safety of Bavencio and Inlyta in Advanced RCC

For patients with low-grade, intermediate-risk non-muscle-invasive bladder cancer (NMIBC), UGN-102 generated robust and durable responses in an analysis of the phase 3 ENVISION and ATLAS studies, according to findings that were presented at the 

Complete response: disappearance of all detectable disease following treatment.

Transurethral resection of bladder tumor (TURBT): surgical procedure to remove bladder tumors via the urethra.

Kaplan-Meier estimate: statistical method to estimate survival probabilities over time.

Micturition urgency: sudden, strong need to urinate.

Pollakiuria: abnormally frequent urination.

Urethral stenosis: narrowing of the urethra, leading to urinary obstruction.

Malaise: general feeling of discomfort or unease.

Disease-free survival (DFS): time from treatment to disease recurrence or death.

Duration of response (DOR): length of time a tumor responds to treatment without progression.

Mitomycin-containing reverse thermal hydrogel: temperature-sensitive gel that delivers mitomycin intravesically for bladder cancer treatment.

Intravesical treatment with UGN-102: non-surgical therapy using a mitomycin-based reverse thermal gel for low-grade bladder cancer.

In the single-arm ENVISION trial, 79.6% of patients with recurrent disease who received UGN-102 (240 patients) achieved a complete response (CR) at three months, and the estimated 12-month CR rate was 82.3%.

In the randomized ATLAS trial, 64.8% of patients with newly diagnosed or recurrent disease who received UGN-102 with or without subsequent transurethral resection of bladder tumor (TURBT; 142 patients) achieved a CR at three months versus 63.6% of those who underwent TURBT (140 patients). The Kaplan-Meier estimated 12-month CR rates in these respective arms were 79.7% and 67.7%.

“These results demonstrate that treatment with UGN-102 results in a high and clinically meaningful durable CR rate in patients with newly diagnosed or recurrent low-grade, intermediate-risk NMIBC,” lead study author Dr. Sandip M. Prasad, of Morristown Medical Center, Atlantic Medical Group, in New Jersey and coauthors wrote in a poster presentation of the data.

The most common side effect observed with UGN-102 across both trials was dysuria, which was reported in 22.5% and 30.4% of patients who received the UGN-102 in ENVISION and ATLAS, respectively.

Previously reported safety findings from ENVISION showed that additional treatment-emergent side effects with UGN-102 included hematuria (8.3%), urinary tract infection (7.1%), pollakiuria (6.7%), fatigue (5.4%), urinary retention (5%), urethral stenosis (4.6%), COVID-19 (3.8%), constipation (3.8%), nausea (3.8%) and micturition urgency (3.3%).

Previously reported safety findings from ATLAS demonstrated that additional treatment-emergent side effects in the UGN-102 and TURBT arms, respectively, included micturition urgency (18%; 7.6%), nocturia (18%; 6.8%), pollakiuria (16%; 6.1%), flatulence (9.4%; 3%), COVID-19 (8.0%; 6.1%), erectile dysfunction (6.5%; 3%), hematuria (6.5%; 4.5%) and malaise (5.8%; 1.5%).

“UGN-102 may represent an efficacious and well-tolerated treatment option for patients with low-grade, intermediate-risk NMIBC,” the authors wrote in the poster.

Among the patients in the ENVISION and ATLAS trials, respectively, 68% and 60% were at least 65 years of age; 98% and 99% were White; and 61% and 70% were male.

The median duration of response (DOR) was not estimable in any of the 3 trial arms because of low recurrence rates. In ENVISION, at a median follow up for DOR of 13.86 months, 17.3% of complete responders (191 patients) had disease recurrence, including low-grade disease (14.1%) and high-grade disease (2.1%). Two patients had died.

In the UGN-102 arm, at a median follow-up for DOR of 12.45 months, 19.6% of complete responders (92 patients) had disease recurrence, including low-grade disease (16.3%) and high-grade disease (3.3%). No patients in this arm had died. In the TURBT arm, at a median follow-up for DOR of 12.16 months, 27% of complete responders (89 patients) had disease recurrence, including low-grade disease (19.1%) and high-grade disease (6.7%). One patient in this arm had died.

TURBT is the current standard of care (SOC) for patients with low-grade, intermediate-risk NMIBC; however, the study authors noted that this treatment method provides inadequate disease control and that patients often need to undergo multiple TURBTs under general anesthesia, which has associated complications, particularly for elderly patients. To address this need, the ENVISION and ATLAS trials studied the efficacy of intravesical treatment with UGN-102, a mitomycin-containing reverse thermal hydrogel, in patients with low-grade, intermediate-risk NMIBC.

In both studies, patients in the UGN-102 arms received UGN-102 via a urinary catheter at 75 milligrams once weekly for six months. In ENVISION, patients with recurrent disease received UGN-102, and those without a CR at three months subsequently received SOC treatment and entered the follow-up period. In ATLAS, patients with newly diagnosed or recurrent disease were randomly assigned to receive UGN-102 or TURBT. Those without a CR with residual low-grade disease subsequently received TURBT and entered the follow-up period. All patients in both trials were examined for bladder cancer recurrence using cystoscopy, urine cytology and for-cause biopsy at three months and at regular intervals thereafter.

In ENVISION, the primary end point was CR at three months. In ATLAS, the primary end point was disease-free survival (DFS). Secondary end points in both trials included DOR and safety.

showed that UGN-102 with or without TURBT generated similar estimated DFS outcomes for patients with newly diagnosed versus recurrent disease. The estimated 15-month DFS rate with UGN-102 was 77.4% in patients with newly diagnosed disease versus 63.2% in those with recurrent disease.

“Treatment of Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer With UGN-102: Results of the Phase 3 ATLAS and ENVISION Studies” by Dr. Prasad S, et al., 

“Response to Primary Chemoablation With UGN-102 in Patients With New or Recurrent LG IR NMIBC: Post-Hoc Analysis of the ATLAS Trial” by Dr. Prasad SM, et al., 

“Primary Chemoablation of Recurrent Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer With UGN-102: A Single-Arm, Open-Label, Phase 3 Trial (ENVISION)” by Dr. Prasad SM, et al., 

“Treatment of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer With UGN-102 ± Transurethral Resection of Bladder Tumor Compared to Transurethral Resection of Bladder Tumor Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS)” by Dr. Prasad SM, et al., 

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UGN-102 demonstrated significant efficacy in treating low-grade, intermediate-risk non-muscle-invasive bladder cancer (NMIBC) in the phase 3 ENVISION and ATLAS trials. In the ENVISION trial, 79.6% of patients achieved a complete response (CR) at three months, with a 12-month CR rate of 82.3%. The ATLAS trial showed similar results, with 64.8% achieving CR at three months. UGN-102 was generally well-tolerated, with dysuria being the most common side effect. The trials suggest UGN-102 as a promising alternative to transurethral resection of bladder tumor (TURBT) for NMIBC management.

Among patients with low-grade, intermediate-risk NMIBC, UGN-102 generated robust, durable responses in an analysis of the phase 3 ENVISION and ATLAS studies.

Ashling Wahner

Dual-Targeting CAR T Therapy Shows Potential in Advanced Kidney Cancer

Personalized Neoantigen Vaccines Show Lasting Tumor Control in Kidney Cancer

Real-World Data Confirms Safety of Bavencio and Inlyta in Advanced RCC

UGN-102 Shows Complete Response Rates in Low-Grade Bladder Cancer

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