Ashling Wahner

For patients with MET exon 14-altered NSCLC, Tepmetko was associated with frequent side effects, although the safety profile is considered manageable.

Among patients with MET exon 14-altered non-small cell lung cancer (NSCLC), treatment with Tepmetko (tepotinib) was associated with a high frequency of side effects, although the safety profile is considered manageable, according to a pooled safety analysis of cohorts A and C of the phase 2 VISION trial.

Notably, these findings were consistent with prior reports from the trial. In the pooled safety analysis of cohorts A and C (313 patients), any-grade side effects occurred in 99% of patients, and grade 3 (severe) or higher side effects were reported in 68.4% of patients. Treatment-related side effects were observed in 91.7% of patients, including grade 3 or higher in 36.1% of patients. Any-grade serious side effects and serious treatment-related side effects occurred in 54.6% and 16% of patients, respectively. Side effects led to dose reductions in 33.2%, treatment interruptions in 43.8% and permanent discontinuation in 15.7% of patients. These rates of treatment-related side effects were 33.2%, 43.8% and 15.7%, respectively. Additionally, 13.7% of patients experienced a side effect that led to death, three of which were treatment related.

The most common treatment-related side effects included peripheral edema (any-grade, 67.7%; grade 3 or higher, 11.8%), hypoalbuminemia (25.2%; 3.8%), nausea (23.3%; 0.6%), diarrhea (22.7%; 0.3%), increased blood creatinine levels (22.0%; 1.3%), alanine aminotransferase (ALT) level elevation (14.1%; 2.2%), decreased appetite (11.5%; 0.3%), aspartate aminotransferase level elevation (11.2%; 1.9%) and amylase level increase (10.5%; 1.9%).

Peripheral edema: swelling of the extremities.

Hypoalbuminemia: low levels of albumin in the blood.

Alanine aminotransferase (ALT) level elevation: an indication of liver damage.

Aspartate aminotransferase level elevation: an indication of liver or muscle damage.

Pleural effusion: accumulation of fluid between the lungs and the chest wall.

ECOG performance status: a method of measuring patients’ ability to complete daily tasks, with lower scores indicating greater independence.

In total, 37.4% of patients required at least one dose reduction. The most common any-grade treatment-related side effect leading to dose reduction, treatment interruption and treatment discontinuation was peripheral edema (15.3%, 18.8%, and 6.1% of patients, respectively). Other treatment-related side effects leading to dose reductions were generalized edema (3.2%), edema (2.2%), pleural effusion (1.6%), increased blood creatinine levels (2.6%), hypoalbuminemia (1.3%), fatigue (1.0%), asthenia (1.0%) and localized edema (1.0%). Other treatment-related side effects leading to treatment interruptions included increased blood creatinine levels (5.8%), generalized edema (4.8%), edema (3.5%), pleural effusion (3.2%), increased ALT levels (2.6%), localized edema (2.2%) and nausea (2.2%). Other treatment-related side effects leading to treatment discontinuation included edema (1.3%), generalized edema (1.0%), pleural effusion (1.0%), interstitial lung disease (1.0%) and pneumonitis (1.0%).

Additionally, health-related quality of life (HRQOL) patient-reported outcome (PRO) scores remained stable with Tepmetko use. Investigators observed no meaningful change in European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) or EuroQol 5-Dimension 5-Level (EQ-5D-5L) scores up to 228 weeks. At the end of treatment, among patients evaluated for HRQOL, the mean change from baseline for the EORTC QLQ-C30 global health status (GHS) was –7.1 and the mean change for the EuroQol visual analogue scales (EQ-VAS) was –10; positive values signified improvement. The mean changes from baseline in the EORTC QLQ-lung cancer (LC13) symptom scores for cough, dyspnea and chest pain, respectively, were –6.1, 7.1 and –2.3; negative values signified improvement. Furthermore, the median time to deterioration of the EORTC QLQ-LC13 symptom scores for cough, chest pain, and dyspnea were 36.5 months, 30.4 months and 5.5 months, respectively.

“Throughout the VISION trial, patients completed questionnaires evaluating their QOL before and while receiving [Tepmetko],” Dr. Enriqueta Felip, lead study author and head of the Thoracic Cancer Unit at Hospital Universitari de la Vall d'Hebron in Barcelona, Spain, and coauthors explained in the conclusion of the poster presentation. “Overall, patients reported that health and QOL remained stable while receiving [Tepmetko]. Specific scores relating to symptoms experienced by patients with lung cancer were improved during treatment for symptoms such as cough and chest pain and remained stable for shortness of breath.”

What Was the Design of the VISION Trial of Tepmetko in Patients With 

The VISION trial was a single-arm study evaluating Tepmetko in patients with advanced NSCLC harboring MET exon 14 skipping alterations.The study evaluated Tepmetko at a dose of 500 mg orally once daily and comprised three cohorts.

Eligible patients were at least 18 years of age, had histologically or cytologically confirmed NSCLC with MET exon 14 skipping alterations detected by liquid biopsy and/or tissue biopsy, measurable disease and an ECOG performance status of 0 or 1. Prior immunotherapy was permitted.

Patients were excluded if their tumors harbored EGFR mutations or ALK rearrangements, if they had received more than two prior lines of systemic therapy, or if they had prior exposure to MET or HGF inhibitors.

What Were the Baseline Patient Demographics in the VISION NSCLC Trial?

The median age of patients with MET exon 14 skipping NSCLC was 72 years. In total, 50.8% of patients were female, 73.8% of patients had an ECOG performance status of 1 and 47.6% of patients had received prior treatment.

At study entry, 47.6% of patients had received at least one prior systemic therapy. The median treatment duration was 7.5 months and 19 patients remained on Tepmetko for at least 48 months.

Felip E, Ferrara R, Veillon R, et al. Safety and patient-reported outcomes with tepotinib in patients with 

ex14 skipping NSCLC: ≥3 years follow-up of VISION. Presented at: 2025 IASLC World Conference on Lung Cancer; September 6-10, 2025; Barcelona, Spain. Poster P3.12.40.

Tepotinib phase II in NSCLC harboring MET alterations (VISION). ClinicalTrials.gov. Updated August 14, 2025. Accessed September 9, 2025. https://www.clinicaltrials.gov/study/NCT02864992

For more news on cancer updates, research and education,

don’t forget to subscribe to CURE®’s newsletters here.

Articles

Tepmetko (tepotinib) treatment in MET exon 14-altered NSCLC patients showed a high incidence of side effects, with 99% experiencing any-grade side effects and 68.4% facing severe ones. Treatment-related side effects were common, leading to dose reductions, interruptions, or discontinuations. Despite these, health-related quality of life scores remained stable, with some symptom improvements. The VISION trial, a single-arm study, evaluated Tepmetko in patients with advanced NSCLC, excluding those with EGFR mutations or ALK rearrangements. The median patient age was 72, with a median treatment duration of 7.5 months.

Tepmetko Associated With Frequent Side Effects for Some With NSCLC

For patients with relapsed/refractory mantle cell lymphoma Lunsumio plus Polivy was associated with durable responses. Image generated by Google Gemini.

Among patients with relapsed/refractory mantle cell lymphoma (MCL) with prior exposure to BTK inhibition, treatment with Lunsumio (mosunetuzumab-axgb) plus Polivy (polatuzumab vedotin-piiq) was associated with durable responses and was found to be well tolerated, clinical trial results have shown.

Findings from an MCL dose-expansion cohort of a phase 2 trial were presented at the 2025 SOHO Annual Meeting.

Among all treated patients (42 patients), the overall response rate (ORR) was 88%; the complete response (CR) and partial response (PR) rates were 79% and 9%, respectively. The efficacy of this combination was observed across high-risk patient subgroups, including those at least 70 years of age (18 patients; ORR, 83%; CR rate, 78%; PR rate, 5%), those who had received prior CAR-T cell therapy (11 patients; 91%; 82%; 9%), those with a Ki-67 score of at least 50% (28 patients; 93%; 79%; 14%), those with pleomorphic or blastoid MCL (16 patients; 94%; 69%; 25%), and those with TP53 mutations or deletions (13 patients; 100%; 92%; 8%).

Overall response rate: patients who responded partially or completely to treatment.

Progression-free survival: the time a patient lives without their disease spreading or worsening.

Overall survival: the time a patient lives, regardless of disease status.

“[Lunsumio] and [Polivy], in my opinion, is going to be a good off-the-shelf option for relapsed/refractory MCL before or after CAR T-cell therapy,” lead study author Dr. Michael L. Wang, said in the presentation.

Wang is a professor in the Department of Lymphoma/Myeloma and the Department of Stem Cell Transplantation in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

What Was the Rationale for Investigating Lunsumio in Combination With Polivy in Patients With MCL?

Lunsumio is a CD20xCD3-directed, T-cell engaging bispecific antibody. Polivy is a CD79-directed antibody-drug conjugate.

“The two are complementary in their mechanisms of action,” Wang noted. “They were synergistic in preclinical studies.”

Previous findings from the dose-expansion large B-cell lymphoma (LBCL) cohort (98 patients) of the phase 2 study showed that at a median follow-up of 23.9 months, Lunsumio plus Polivy elicited an ORR of 59.2% and a CR rate of 45.9%. Furthermore, the median duration of CR was not reached.

What Was the Design of the MCL Portion of the Phase 2 Study of Lunsumio Plus Polivy in Relapsed/Refractory MCL?

This phase 2 study is investigating the efficacy, safety, pharmacokinetics and pharmacodynamics of Lunsumio plus Polivy in patients with B-cell non-Hodgkin lymphoma, including LBCL, follicular lymphoma and MCL.

Patients received the investigational combination in a fixed-duration treatment approach that included Lunsumio administered subcutaneously at 45 mg in 21-day cycles (5-mg step-up dosing occurred in cycle 1) for a total of 17 cycles; and intravenous Polivy administered at 1.8 mg/kg on day 1 of cycles 1 through 6. Hospitalization was not required. Patients received corticosteroid premedication before each dose in cycle 1.

What Were the Baseline Characteristics of Patients Included in the Trial?

Patients had a median age of 68 years and had received three prior lines of therapy. Prior therapies included BTK inhibition (100%), CAR T-cell therapy (26%) and autologous stem cell transplant (31%). In total, 93% of patients were refractory to their last prior therapy. TP53 mutations or deletions were present in 39% of patients, 38% of patients had blastoid or pleomorphic disease, and 43% of patients had bone marrow involvement. Ki-67 scores of at least 30% and at least 50% were reported in 76% and 67% of patients, respectively. Additionally, 48% of patients had a simplified International Prognostic Index for MCL score of at least 6. Overall, 71% of patients had at least three high-risk features.

“This is a high-risk, heavily treated population,” Wang contextualized.

What Additional Efficacy Data Were Observed With Lunsumio Plus Polivy?

The responses observed with this combination were early and durable, Wang noted. At a median follow-up of 15.9 months, among all responders (37 patients), the median time to first response was 2.7 months, the median DOR was not reached and the 12-month response rate was 66%. Among complete responders (33 patients), the median time to first CR was 2.8 months, the median duration of CR was not reached and the 12-month response rate was 71.9%.

Among all treated patients, the median progression-free survival (PFS) was 18.6 months, and the 12-month PFS rate was 74.8%. The median overall survival (OS) was 20.7 months and the 12-month OS rate was 83.1%.

What Was the Safety Profile of Lunsumio Plus Polivy in Patients With MCL?

All patients experienced side effects, and 93% of patients experienced treatment-related side effects. The rates of grade 3 (severe)/4 (life-threatening) side effects and treatment-related side effects were 69% and 60%, respectively. Serious side effects and treatment-related side effects were reported in 62% and 41% of patients, respectively. Grade 5 (fatal) side effects and treatment-related side effects occurred in 12% and 2% of patients, respectively; these included COVID-19 pneumonia (three patients), pneumonia (one patient) and West Nile virus encephalitis (one patient). Treatment discontinuation related to side effects and treatment-related side effects occurred in 24% and 12% of patients, respectively. Patients received a median of 15 Lunsumio cycles and six Polivy cycles.

Side effects and treatment-related side effects that occurred in at least 20% of patients included fatigue, injection site reaction, neutropenia/decreased neutrophil counts, diarrhea, cytokine release syndrome (CRS), nausea, dyspnea, constipation, cough, headache, pyrexia, thrombocytopenia/decreased platelet counts, COVID-19 and myalgia. Side effects of interest included injection site reaction (grade 1 (mild), 52%; grade 2 (moderate), 5%), peripheral neuropathy (grade 1, 29%; grade 2, 12%), immune effector cell–associated neurotoxicity syndrome (grade 2, 2%), infections (any grade, 71%; grade 3/4, 14%; grade 5, 12%), tumor flare (grade 1, 5%; grade 2, 7%), neutropenia/decreased neutrophil counts (any grade, 45%; grade 3/4, 41%), and febrile neutropenia (grade 3, 5%).

Notably, B-cell depletion occurred rapidly during treatment, and investigators observed recovery of B-cell counts following treatment.

Wang ML, Kamdar M, Assouline S, et al. Fixed-duration outpatient subcutaneous mosunetuzumab + polatuzumab vedotin shows robust efficacy in a phase II study of relapsed/refractory post-BTKi mantle cell lymphoma. Presented at: 2025 SOHO Annual Meeting. September 3-6, 2025; Houston, TX. Abstract MCL-1493.

Budde LE, Olszewski AJ, Assouline S, et al. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. 

. 2024;30(1):229-239. doi:10.1038/s41591-023-02726-5

A study to evaluate the safety and efficacy of mosunetuzumab (BTCT4465A) in combination with polatuzumab vedotin in B-cell non-Hodgkin lymphoma. ClinicalTrials.gov. Updated November 29, 2024. Accessed September 6, 2025. https://www.clinicaltrials.gov/study/NCT03671018

Lunsumio (mosunetuzumab-axgb) combined with Polivy (polatuzumab vedotin-piiq) demonstrated significant efficacy and tolerability in patients with relapsed/refractory mantle cell lymphoma (MCL) previously treated with BTK inhibitors. The phase 2 trial showed an overall response rate of 88%, with complete and partial response rates of 79% and 9%, respectively. The combination was effective across high-risk subgroups, including those with prior CAR-T therapy and TP53 mutations. Despite a high incidence of side effects, the treatment was generally well-tolerated, with manageable safety profiles and durable responses.

For patients with relapsed/refractory mantle cell lymphoma Lunsumio plus Polivy was associated with durable responses.

Lunsumio plus Polivy Associated With Responses in MCL

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. 

For more news on cancer updates, research and education, 

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.

Ashling Wahner

Tepmetko Associated With Frequent Side Effects for Some With NSCLC

Lunsumio plus Polivy Associated With Responses in MCL

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

Personalized Neoantigen Vaccines Show Lasting Tumor Control in Kidney Cancer

Latest News