Inlyta (axitinib) / Pfizer - LARVOL DELTA

The efficacy of immunotherapy in alveolar soft part sarcoma (ASPS): A case report (ASH 2025) - "Informed by prior pediatric ASPS studies, his initial treatment regimen consisted of axitinib and pembrolizumab, a TKI and ICI respectively...In the setting of worsening disease/evolving mixed response, the patient was transitioned to a similar regimen of atezolizumab and cabozantinib...By analyzing this patient's unique ASPS tumor characteristics, it became possible to develop a targeted and effective treatment approach. Overall, this case supports the synergistic effect of TKIs and ICIs on ASPS while highlighting their limited side effect profile, suggesting an opportunity for future studies on combinations of immunotherapies."

Case report • Clinical • IO biomarker • Alveolar Soft Tissue Sarcoma • Cough • Respiratory Diseases • Sarcoma • Solid Tumor • ASPSCR1 • PD-L1 • TFE3

Novel BCR::ABL1 fusion alongside T315I reveals mechanism for dual ponatinib/asciminib resistance and proves sensitive to addition of axitinib (ASH 2025) - "In a screen of drug combinations, we identified axitinib as a potent agent when combined withponatinib, nilotinib, asciminib, or ribastinib, ABL1 inhibitors that target the inactive conformation.Given that axitinib binds both active and inactive conformations of the kinase, we reason that thethree-drug combination enforces a shift in the conformational dynamics of a BCR::ABL1 oligomer,stabilizing the inactive state for even this highly activated BCR::ABL1e6a3/T315I kinase. In conclusion, we have identified and characterized a novel BCR::ABL1 fusion (e6a3) thattogether with T315I represents a compound mutation that is pan-resistant to all currentlyapproved ABL1 inhibitors, but which remains fully sensitive to a triple combination therapycomprising axitinib, ponatinib, and asciminib. These preclinical findings demonstrate theremarkable mutability of the BCR::ABL1 kinase when under selection by even the most potent ofABL1 kinase inhbitors, and provides a strong rationale..."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1 • CD34

Iparomlimab and Tuvonralimab Injection in Combination With Lenvatinib or Axitinib for the Treatment of Locally Advanced or Metastatic Clear Cell Renal Cell Carcinoma That Has Failed First-Line Systemic Therapy (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Tianjin Medical University Cancer Institute and Hospital

New P2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Long term real-world outcomes of first-line immunotherapy (IO) and vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) combination in metastatic clear cell renal cell carcinoma (mRCC): Does the type of IO or VEGF-TKI matter? (ESMO Asia 2025) - "Background: First-line treatment of mRCC involves a combination of IO with a VEGF-TKI, or dual IO using nivolumab + ipilimumab...31 (60%) patients received nivolumab and 21 pembrolizumab, while the VEGF-TKI was lenvatinib in 34 (65%) and axitinib in 18... The combination of IO and VEGF-TKIs demonstrated robust efficacy in our mRCC cohort, with high ORR, minimal primary progression, and favourable survival. We recommend using IO in combination with a VEGF-TKI, based on availability, side-effects and experience, as no significant differences were observed between individual IO agents or VEGF-TKIs. Grade 3/4 IRAEs may occur, highlighting the need for early detection and timely intervention."

Clinical • Metastases • Real-world • Real-world evidence • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

SHOX2-Mediated lymphatic metastasis in pT1 non-clear cell renal carcinoma: Biomarker-driven risk stratification and combined-modality management (ESMO Asia 2025) - "SHOX2 drives lymphatic metastasis in pT1 nccRCC via ECM-EMT crosstalk. A precision perioperative strategy is proposed: (1) Preoperative mSHOX2 liquid biopsy for LNM risk assessment; (2) 99mTc-sulfur colloid lymphoscintigraphy-guided lymph node dissection in high-risk cases; (3) Postoperative adjuvant toripalimab-axitinib combination for SHOX2-positive patients. Multicenter validation of this biomarker-directed framework is warranted to optimize therapeutic precision in nccRCC."

Biomarker • Clear Cell Renal Cell Carcinoma • Kidney Cancer • Non Clear Cell Renal Cell Carcinoma • Oncology • Renal Cell Carcinoma • Solid Tumor • SHOX2

Immune-related adverse events associated with first-line immune checkpoint inhibitors-based therapy for metastatic renal cell carcinoma (ESMO Asia 2025) - "Background: To assess Immune-related toxicity and safety of first-line immune checkpoint inhibitors-based therapy in metastatic renal cell carcinoma (mRCC) patients treated in real-world clinical practice. The retrospective study included data of 194 patients ≥18 years, with verified mRCC, treated with upfront combined immunotherapy, IO-IO (nivolumab + ipilimumab, 94 (48.5%) patients) or immune-targeted therapy, IO-TKI (100 (51.5%) patients: pembrolizumab + axitinib (85 (43.8%)) or lenvatinib (10 (5.2%)), nivolumab + cabozantinib (5 (2.6%)) from 07.07.2019 to 22.10.2024 at Moscow City Hospital named after S.S. Yudin... Real-world practice data confirmed results of randomized trials regarding with irAEs rate and spectrum but demonstrated higher severe and multiple irAEs frequency in mRCC patients treated with upfront immune checkpoint inhibitors-based therapy. IO-IO was associated with higher rate of multiple irAEs and immune-related renal toxicity comparing IO-TKI."

Adverse events • Checkpoint inhibition • Clinical • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Fruquintinib monotherapy as second-line (2L) treatment in locally advanced or metastatic renal cell carcinoma (RCC): Results from phase II part of FRUSICA-2 (ESMO Asia 2025) - P2/3 | "Background: FRUSICA-2 is a randomized, open-label, active-controlled phase 2/3 study (NCT05522231) designed to evaluate the efficacy and safety of Fruquintinib (F) + Sintilimab versus Axitinib or Everolimus monotherapy for 2L treatment of RCC. Results from this F monotherapy of the FRUSICA-2 indicated a comparable anti-tumor efficacy compared with other 2L VEGFR-TKI monotherapies, along with a manageable safety profile in 2L RCC pts after first-line VEGFR-TKI therapy."

Clinical • Metastases • Monotherapy • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Study of Adaptive Immunotherapy With VEGFR-TKI in Patients With Advanced RCC (clinicaltrials.gov) - P2 | N=75 | Suspended | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Recruiting ➔ Suspended

Trial suspension • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Combination immunotherapy in Japanese patients with advanced renal cell carcinoma: bridging gaps between clinical trials, real-world evidence, and the potential value of adverse events-a narrative review. (PubMed, Transl Cancer Res) - "Nivolumab plus ipilimumab (NIVO + IPI) and various ICI + TKI regimens (avelumab + axitinib, pembrolizumab + axitinib, nivolumab + cabozantinib, pembrolizumab + lenvatinib) have shown superior efficacy to sunitinib in pivotal trials...TRAEs show promise as prognostic markers in NIVO + IPI but require further validation in ICI + TKI. Prospective multicenter registries with standardized adverse event reporting, coupled with translational studies, are needed to refine regimen selection and personalized therapy."

Adverse events • HEOR • IO biomarker • Journal • Real-world evidence • Review • Genito-urinary Cancer • Kidney Cancer • Non Clear Cell Renal Cell Carcinoma • Oncology • Renal Cell Carcinoma • Solid Tumor

Seleno-L Methionine (SLM)-Axitinib-Pembrolizumab (clinicaltrials.gov) - P1/2 | N=55 | Active, not recruiting | Sponsor: Mohammed Milhem | Recruiting ➔ Active, not recruiting

Enrollment closed • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Second-line cabozantinib after failure of immune-based therapy in patients with metastatic renal cell carcinoma: Analysis of the RENIS II registry (EMUC 2025) - "First-line treatment consisted of ipilimumab/nivolumab in 25 patients, and avelumab/axitinib or pembrolizumab/lenvatinib in the remaining 25 subjects...No unexpected serious adverse events were reported during treatment. Conclusions Data from the RENIS registry confirm the effectiveness and safety of cabozantinib in the second-line setting in the real-world clinical practice in the Czech Republic."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Restricted Mean Survival Time–Based Comparative Effectiveness of First-Line Immune Checkpoint Inhibitor Combinations in Metastatic Renal Cell Carcinoma (SUO 2025) - " Compared with sunitinib, OS dRMST was 4.15 months (95% CI: 1.86–6.45, p<0.001) for Nivolumab + Cabozantinib (NIVO–CABO), 3.53 (1.43–5.62, p=0.001) for Lenvatinib + Pembrolizumab (LEN–PEM), 2.75 (0.97–4.53, p=0.002) for Nivolumab + Ipilimumab (NIVO–IPI), and 2.68 (0.77–4.58, p=0.005) for Pembrolizumab + Axitinib (PEM–AXI)... RMST-based analysis enables nuanced comparison of ICI regimens in mRCC, highlighting modest OS benefit, greater PFS separation, cost differences, and distinct toxicity burdens. Nivolumab + Cabozantinib demonstrated the greatest OS benefit, while Lenvatinib + Pembrolizumab achieved the highest PFS gain. These findings underscore the importance of integrating multiple treatment attributes—beyond hazard ratios—into personalized treatment decision-making."

Checkpoint inhibition • Clinical • HEOR • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

REVISITING CYTOREDUCTIVE NEPHRECTOMY IN METASTATIC RENAL CELL CARCINOMA: REAL-WORLD EVIDENCE OF SURVIVAL BENEFIT IN THE ERA OF MODERN IMMUNOTHERAPY AND TARGETED THERAPY (SUO 2025) - "Evidence from the Cancer du Rein Metastatique Nephrectomie et Antiangiogéniques (CARMENA) and the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients with Metastatic Kidney Cancer (SURTIME) trials have questioned the role of CRN...Using relevant ICD-10 codes and CPT codes, cohorts of patients with mRCC receiving any kind of systemic therapy (n= 1776), Axitinib and Pembrolizumab (n= 470), Cabozantinib and Nivolumab (n=774), Lenvatinib and Pembrolizumab (n = 246), and Ipilimumab and Nivolumab (n= 958), were identified... Although the use of CRN in patients with mRCC has steadily declined since 2012, our large-scale real-world analysis demonstrates that CRN is associated with a significant survival benefit in most patients with mRCC receiving contemporary systemic combination therapy. These findings highlight the continued relevance of CRN in well selected patients and underscore the need to revisit CRN in the immunotherapy era with prospective..."

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Assessment of advanced clear cell renal cancer patients treated with first-line immuno-combinations: A monocentric Latin American experience (EMUC 2025) - "First-line therapies included nivolumab + ipilimumab (63%), pembrolizumab + axitinib (18.5%), and pembrolizumab + lenvatinib (14.8%)...While our findings are generally consistent with international cohorts, the observed differences in age, BMI distribution, and treatment selection underscore the need for regional data. Future research should focus on prospective, multicenter studies with larger sample sizes and longer follow-up to better understand prognostic factors and optimize treatment strategies in this population."

Clinical • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Second-line therapies of Metastatic Renal Cell Carcinoma (mRCC) after 1st line immune-combinations (ICI-combos) (Meet-URO 33 study) (EMUC 2025) - "According to the ICI-combo type, 36% of patients treated with Pembrolizumab + Axitinib, 32% with Nivolumab + Ipilimumab, 11% with Nivolumab + Cabozantinib and 9% with Pembrolizumab + Lenvatinib started a 2nd line therapy...Drug combinations (Lenvatinib + Everolimus/Belzutifan) rise as emerging therapies, especially in younger and prognostically unfavorable patients. Further survival and response analyses are planned."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

AREN1721: A Study to Compare Treatments for a Type of Kidney Cancer Called TFE/Translocation Renal Cell Carcinoma (tRCC) (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jan 2026 ➔ Nov 2026

Trial completion date • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • TFE3

High LAG-3 RNA Levels Predict Response, Not Survival, in Metastatic RCC (Targeted Oncology) - "The discordance between response and survival may be explained by the specific immunological profile associated with LAG3. High expression of the gene was linked to a 'complex immunological phenotype' characterized as both inflamed and exhausted, explained Rana McKay, MD...during a presentation of the study."

Audio • Renal Cell Carcinoma

The Association between Combination-Based Immunotherapy and Thrombotic Events in Patients with Metastatic Renal Cell Carcinoma (ASH 2024) - "The IO/IO regimen was defined as ipilimumab plus nivolumab, while the IO/TKI regimen included nivolumab or pembrolizumab combined with a TKI such as axitinib, cabozantinib, or lenvatinib...Conclusion : There was no difference in the risk of venous and arterial thromboembolic events between mRCC patients receiving the IO/IO regimen and those receiving the IO/TKI regimen. However, patients on the IO/IO regimen had an increased risk of mortality compared to those on the IO/TKI regimen."

Clinical • Metastases • Cardiovascular • Genito-urinary Cancer • Hematological Disorders • Ischemic stroke • Myocardial Infarction • Oncology • Renal Cell Carcinoma • Respiratory Diseases • Solid Tumor • Venous Thromboembolism

A comparative study of two surgical robotic systems for perioperative outcomes of robot-assisted radical cystectomy: A propensity score-matched analysis (EMUC 2025) - "First-line therapies included nivolumab + ipilimumab (63%), pembrolizumab + axitinib (18.5%), and pembrolizumab + lenvatinib (14.8%)...No statistically significant associations were observed between BMI >25, BMI >30, or elevated NER and progression or mortality (all p > 0.05). Conclusions Although the small sample size, our findings suggest that perioperative outcomes of RARC using the novel surgical robot system, hinotori, are comparable to those using da Vinci system."

Bladder Cancer • Genito-urinary Cancer • Solid Tumor

Network Meta-Analysis for an Efficacy Assessment of Avelumab Axitinib in the First-Line Treatment of International Metastatic RCC Database Consortium (IMDC) Favorable Risk Patients With Advanced Renal Cell Carcinoma (ARCC) (ISPOR-EU 2025) - "Relevant treatment comparators with reported results in this subgroup included sunitinib, nivolumab + ipilimumab (nivo + ipi), pembrolizumab + lenvatinib (pem + len) and nivolumab + cabozantinib (nivo + cabo). Subgroup data from four randomized controlled trials (RCTs) were suitable for indirect treatment comparisons (JAVELIN Renal 101 [ave + axi, n=188], CheckMate 214 [nivo + ipi, n=249], CheckMate 9ER [nivo + cabo, n=146] and CLEAR [pem + len, n=234])... These findings support the role of ave + axi as a 1L treatment option for IMDC favorable risk aRCC patients. Results have shown that ave + axi performed numerically better than 3 of the 4 comparator treatments for OS and better than 2 of the 4 comparators for PFS, with numerically similar results to 1 comparator in both OS and PFS."

Metastases • Retrospective data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Outcomes of immune-checkpoint inhibitors rechallenge in metastatic clear cell renal cell carcinoma: results from a global real-world evidence study. (SITC 2025) - "The most common first-line regimens were nivolumab (N) + cabozantinib (44.1%), N + ipilimumab (26.5%), pembrolizumab (P) + axitinib (20%), and P + lenvatinib (8.4%)...Median OS was 34.9 months for rechallenge ≥ 6 months vs. 19.4 months for rechallenge at <6 months (log-rank p = 0.014). HR = 1.693; 95% CI: 1.108–2.585"

Checkpoint inhibition • Clinical • HEOR • Metastases • Real-world • Real-world evidence • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Prognostic impact of early tumor shrinkage in patients with metastatic renal cell carcinoma treated with first-line ICI-based combination therapies (EMUC 2025) - "Results The treatment regimens included nivolumab plus ipilimumab (n=86, 45.3%), avelumab plus axitinib (n=26, 13.7%), pembrolizumab plus axitinib (n=15, 7.9%), nivolumab plus cabozantinib (n=23, 12.1%), and pembrolizumab plus lenvatinib (n=40, 21.1%)...Of these significant factors, only prior nephrectomy, bone or liver metastasis and early tumor shrinkage were shown to be independently associated with OS on multivariate analysis. Conclusions Early tumor shrinkage was independently associated with favorable OS, suggesting its potential as a prognostic indicator in mRCC treated with first-line ICI-based combination therapy."

Clinical • Combination therapy • IO biomarker • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Endocrine adverse events as an efficacy biomarker in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitors-based therapy (ESMO-IO 2025) - "We evaluated the association of therapy-induced EAEs with antitumor efficacy in patients with metastatic renal cell carcinoma (mRCC) treated with upfront ICI-based therapy in real-world practice.Methods the retrospective study included data of 194 patients ≥18 years, with verified mRCC, treated with upfront combined immunotherapy, ICI-ICI (nivolumab + ipilimumab, 94 (48.5%) patients) or immune-targeted therapy, ICI-TKI (100 (51.5%) patients: pembrolizumab + axitinib (85 (43.8%)) or lenvatinib (10 (5.2%)), nivolumab + cabozantinib (5 (2.6%)) from 07.07.2019 to 22.10.2024 at Moscow City Hospital named after S.S. Yudin...In the ICI-ICI group EAEs were associated with both PFS (HR=2.1 (95%CI: 1.1-4.1); р=0.026) and OS benefit (HR=2.8 (95%CI: 1.4-5.6); р=0.003). The ICI-TKI group patients with EAEs had better PFS comparing with those without EAEs (HR=3.3 (95%CI: 1.6-6.7); р=0.001).Conclusions in mRCC patients, treated with both upfront ICI-ICI and ICI-TKI combinations,..."

Adverse events • Biomarker • Checkpoint inhibition • Clinical • IO biomarker • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Systemic targeting of aberrant neovascular tufts using trehalose-dendrimer nanocarriers for the treatment of proliferative retinopathies. (PubMed, Theranostics) - " To date, there are no organic nanoparticles that localize selectively in aberrant neovascular tufts at the site of pathology in retina when systemically administered. By eliminating the need for invasive intravitreal injections and addressing systemic toxicities, Tre-D-Axitinib introduces a novel systemic nanotherapeutic strategy with broad implications for treating ischemic retinopathies."

Journal • Age-related Macular Degeneration • Ophthalmology • Retinal Disorders

Dual-Functionalized Mesoporous Silica Nanoparticles for Topical Axitinib Delivery to the Posterior Eye Segment. (PubMed, Eur J Pharm Sci) - "This work introduces a novel nanocarrier system capable of overcoming the longstanding delivery barrier to the posterior eye segment via eyedrops, offering a safe, effective, and clinically translatable alternative to IVT injections. The modular design of AXT@dual-MSNs also holds promise for expanding topical access to other hydrophobic or labile therapeutics targeting retinal diseases."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration