axitinib / Generic mfg. - LARVOL DELTA

A phase II trial of sitravatinib + nivolumab after progression on immune checkpoint inhibitor in patients with metastatic clear cell RCC. (PubMed, Oncologist) - P2 | "In this small phase 2 trial with limited sample size due to early termination, sitravatinib plus nivolumab demonstrated a manageable safety profile and produced modest clinical benefit. The observed responses occurred in patients who did not receive prior treatment with cabozantinib or lenvatinib. (ClinicalTrials.gov Identifier: NCT04904302)."

Checkpoint inhibition • Journal • P2 data • Clear Cell Renal Cell Carcinoma • Oncology • Renal Cell Carcinoma

Exploratory analysis from NEOAVAX, a neoadjuvant trial of avelumab/axitinib in patients (pts) with localized renal cell carcinoma (RCC) who are at high risk of relapse after nephrectomy. (ASCO 2025) - P2 | "Pathologic response and IHC post-treatment influx of CD8+CD39+ TILs associates with prolonged disease-free survival following neoadjuvant avelumab/axitinib. Particularly, pts with MPR had distinct spatial co-localisation gene signatures of tumour and immune cells in the TME. Despite 3 months of treatment, 62.5% of pts had no pathologic responses (defined by INMC as >50% vital tumour remaining in the tumour bed)."

Clinical • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • ENTPD1 • FOXP3 • GZMB

Pembrolizumab-axitinib versus nivolumab-cabozantinib as first-line therapy in patients with metastatic renal cell carcinoma: a retrospective real-world comparison (ARON-1). (PubMed, Cancer Immunol Immunother) - "In this certainly biased retrospective comparison, NC demonstrated superior ORR and longer PFS compared to PA in mRCC. These findings underscore the importance of considering individual patient characteristics and risk profiles when selecting first-line therapy for mRCC."

Clinical • Journal • Real-world evidence • Retrospective data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Gut-associated checkpoint as a prognostic biomarker in metastatic renal cell carcinoma (mRCC): Results from a randomized first-line clinical trial. (ASCO 2025) - P3 | " Using a Luminex assay, sMAdCAM-1 levels were measured in available plasma samples at baseline from 612 pts (69% of the intent-to-treat population) from the phase III JAVELIN Renal 101 trial (NCT02684006), which compared avelumab + axitinib with sunitinib in previously untreated mRCC pts. Higher sMAdCAM-1 is associated with improved outcomes to 1st line regimens in mRCC. sMAdCAM-1 may have an added prognostic value to IMDC. As a diagnostic test of gut dysbiosis, it might guide the selection of pts eligible to microbiota-modulating strategies."

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

Validation of a 15-Gene Prognostic Signature in Metastatic Clear Cell Renal Cell Carcinoma. (PubMed, JCO Precis Oncol) - "The 15G score was independently prognostic in metastatic ccRCC among patients receiving different systemic therapy regimens."

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

Pembrolizumab plus axitinib versus sunitinib for advanced clear cell renal cell carcinoma: 5-year survival and biomarker analyses of the phase 3 KEYNOTE-426 trial. (PubMed, Nat Med) - P3 | "Prospective clinical investigations are needed for biomarker-directed treatment for advanced RCC. ClinicalTrials.gov identifier: NCT02853331 ."

Biomarker • IO biomarker • Journal • P3 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Von Hippel-Lindau Syndrome • BAP1 • PBRM1 • PD-L1 • VHL

Sintilimab Plus Axitinib for Advanced Fumarate Hydratase-Deficient Renal Cell Carcinoma: A Phase 2 Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P2 | "This combination therapy warrants further validation in a randomized clinical trial. ClinicalTrials.gov Identifier: NCT04387500."

Clinical • Journal • P2 data • Dyslipidemia • Genito-urinary Cancer • Hematological Disorders • Hypertriglyceridemia • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • FH

Fruquintinib (FRUQ) plus sintilimab (SIN) versus axitinib (AXI) or everolimus (EVE) monotherapy as 2L treatment in pts with locally advanced or metastatic renal cell carcinoma (RCC): Results from phase III part of a randomized, open-label, active-controlled phase II/III study (FRUSICA-2) (ESMO 2025) - P2/3 | "The incidences of grade ≥3 TEAEs (71.4% vs 58.8%), TEAEs leading to treatment discontinuation (17.6% vs 9.6%), and fatal TEAEs (4.2% vs 4.4%) were comparable between groups. Table: 2592MO Efficacy Results by IMDC Prognostic Risk ITT set (BIRC-assessed) IMDC risk factor Number of IMDC risk factor Favorable-risk Intermediate-risk Poor-risk 0-1 risk factors FRUQ+ SIN N=33 AXI/EVE N=32 FRUQ+ SIN N=73 AXI/EVE N=72 FRUQ+ SIN N=13 AXI/EVE N=11 FRUQ+ SIN N=76 AXI/EVE N=73 mPFS, months NR 8.31 22.21 6.97 9.69 4.21 24.87 8.31 Unstratified HR (95% CI) 0.270 (0.117, 0.620) 0.352 (0.221, 0.562) 0.591 (0.203, 1.721) 0.278 (0.168, 0.461) Unstratified log-rank p * 0.0009 <0.0001 0.3267 <0.0001 ORR (%) 63.6 25.0 61.6 23.6 46.2 27.3 63.2 26.0 Odds ratio (95% CI) 5.250 (1.608, 17.712) 5.200 (2.394, 11.435) 2.286 (0.315, 19.098) 4.872 (2.292, 10.456) p * 0.0019 <0.0001 0.3514 <0.0001 *Two-sided Conclusions FRUQ+SIN demonstrated superior mPFS and manageable safety compared..."

Clinical • Metastases • Monotherapy • P2/3 data • P3 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Using liquid biopsies to classify adenoid cystic carcinoma into clinically relevant subtypes (ESMO 2025) - P2 | "Methods We profiled the specimens from twenty-two ACC patients enrolled in a clinical trial assessing the efficacy of axitinib plus avelumab (NCT03990571). Conclusions Subtyping of ACC is feasible not only from tissue but also from liquid biopsies, allowing minimal invasive and longitudinal analysis of subtypes. This novel method might enable further personalized trials in ACC."

Biopsy • Clinical • Liquid biopsy • Adenoid Cystic Carcinoma • Oncology • NOTCH1 • TP63

Soluble MAdCAM-1 predicts outcomes in patients with metastatic renal cell carcinoma: Results from three independent clinical trials (ESMO 2025) - P2, P3 | "Methods sMAdCAM-1 was measured using the Human Luminex Discovery Assay in plasma from 1,051 patients across the phase 3 JAVELIN Renal 101 trial (1 st line avelumab + axitinib vs. sunitinib) as training cohort and the phase 2 SURF (1 st line sunitinib) and NIVOREN (nivolumab post-TKI) trials as validation cohorts. Conclusions Higher sMAdCAM-1 levels at baseline or their increase during the first cycles of therapy were associated with improved outcomes in patients with mRCC. Our study supports a paradigm shift in the management of mRCC, paving the way to biomarker-guided clinical trials investigating microbiota-targeted interventions aimed at enhancing the efficacy of standard ICI-based therapies."

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

NF1/2 mutations predict favorable benefit from immune checkpoint inhibitor-based therapies over VEGFR/mTOR inhibitors in clear cell renal cell carcinoma. (PubMed, Clin Exp Med) - "This tendency was not changed by everolimus (HR = 2.66), but was abrogated slightly by sunitinib (HR = 1.59) and considerably by ICI-based therapies, including nivolumab monotherapy (HR = 1.12), atezolizumab plus bevacizumab (HR = 1.10), and avelumab plus axitinib (HR = 0.69). Overall, our findings suggest that NF1/2 mutations can serve as predictive biomarkers for favorable benefits from ICI-based treatments over VEGFR/mTOR inhibitors in advanced ccRCCs."

Checkpoint inhibition • IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Inflammatory Arthritis • Oncology • Solid Tumor • NF1

Cross-trial validation of molecular subtypes in patients with metastatic clear cell renal cell carcinoma (RCC): The JAVELIN Renal 101 experience. (ASCO 2022) - P3 | "Molecular clusters of patients have been identified and correlated with outcomes in the phase 3 IMmotion151 (IM151) trial of atezolizumab + bevacizumab (IO+VEGF) vs. sunitinib (Sun) (Motzer, Cancer Cell 2020 &JAMA Oncol 2021). Avelumab+axitinib (AA) is an approved IO+VEGF combination in mRCC... We were able to largely validate the molecular clusters classification and some of the associations with survival outcomes from IM151 in the JR101 clinical trial cohort. Biomarkers of specific VEGF+IO combinations in mRCC should be prospectively validated in randomized trials. >Cluster 7 separately was excluded as it contains 1 patient per treatment arm."

Clinical • IO biomarker • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Renal Cell Carcinoma • Solid Tumor

AREN1721, a randomized phase 2 trial of axitinib+nivolumab combination therapy vs. single agent nivolumab for the treatment of TFE/translocation renal cell carcinoma (tRCC) across all age groups, an NCI National Clinical Trials Network (NCTN) phase 2 study. (ASCO 2025) - P2 | "Nivolumab+axitinib combination therapy was statistically more active than nivolumab single agent therapy, which itself was inactive. Whether anti-PD1 pathway inhibitors add benefit to anti-VEGF therapy for tRCC remains to be determined. Optimizing trial recruitment is critical for this rare but aggressive cancer."

Clinical • Combination therapy • P2 data • Genito-urinary Cancer • Oncology • Pediatrics • Renal Cell Carcinoma • Solid Tumor • TFE3

Peripheral and tumor cytokines in exceptional responders to immunotherapy: Results from a phase III trial (ESMO 2025) - "Cytokines were z-scored, and group differences between exceptional responders (ER) and patients with progressive disease (PD) in the PD-L1 inhibitor Avelumab + Axitinib arm were assessed using two-tailed Wilcoxon rank-sum tests. In contrast, patients with PD exhibited intratumoral immunosuppression, potentially contributing to resistance. Legal entity responsible for the study Renee Maria Saliby."

P3 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • IL10 • IL1B

Avelumab Plus Intermittent Axitinib in Previously Untreated Patients with Metastatic Renal Cell Carcinoma. The Tide-A Phase 2 Study. (PubMed, Eur Urol) - "The TIDE-A study demonstrates that the withdrawal of VEGFR-TKI with ICI maintenance is feasible for selected mRCC patients with evidence of a response to the VEGFR-TKI + ICI combination employed in first-line therapy. Axitinib interruption with avelumab maintenance leads to decreased side effects and should be investigated further as a new strategy to delay tumour progression."

Journal • Metastases • P2 data • Genito-urinary Cancer • Hepatology • Kidney 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

A phase II trial of sitravatinib plus nivolumab after progression on prior immune checkpoint inhibitor (ICI) in patients with metastatic clear cell renal cell carcinoma (ccRCC). (ASCO 2024) - P2 | " In this investigator-initiated, phase II, multicenter trial (NCT04904302), patients with progressive metastatic ccRCC after 1-2 lines of treatment were enrolled into three cohorts: Cohort A) progression on 1L nivolumab + ipilimumab, Cohort B) progression on 1L pembrolizumab + axitinib or 2L anti-PD-1 therapy after receiving 1L VEGF-targeted monotherapy, Cohort C) progression on 1L or 2L cabozantinib or lenvatinib +/- everolimus either before, after, or in combination with anti-PD-1 ICI... In this small phase 2 trial with limited sample size due to early termination, sitravatinib plus nivolumab demonstrated a manageable safety profile and produced modest clinical benefit. The observed responses occurred in patients who did not receive prior treatment with cabozantinib or lenvatinib."

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

Distinct pathways of disease progression with dual checkpoint blockade versus immunotargeted therapy in metastatic renal cell carcinoma. (PubMed, Urol Oncol) - "Nivo-Ipi was associated with more frequent development of new metastatic lesions, particularly in the lungs, bones, and lymph nodes, while axitinib-based combinations more often resulted in regrowth of existing disease with higher rates of adrenal involvement."

Checkpoint inhibition • Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Time-Dependent Comparative Effectiveness of First-Line Treatment for Metastatic Clear Cell Renal Cell Carcinoma: A Restricted Mean Survival Time-Based Network Meta-analysis. (PubMed, Target Oncol) - "Given the frequent proportional hazards violations, hazard ratio-only syntheses are insufficient for modern immune checkpoint inhibitor-based regimens. In the restricted mean survival time-based network meta-analysis, Pembrolizumab + Lenvatinib delivered rapid disease control, and Ipilimumab + Nivolumab showed the greatest late survival advantage in IMDC intermediate/poor-risk."

HEOR • Journal • Retrospective data • Review • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Pyroptosis in Peripheral Neuropathy: From Molecular Mechanisms to Therapeutic Targeting. (PubMed, CNS Neurosci Ther) - "Targeting pyroptosis is a novel therapeutic avenue for PN. This review synthesizes current mechanistic understanding, evaluates preclinical therapeutic strategies, and delineates crucial future directions, including elucidating gasdermin diversity, validating PANoptosis, and bridging the translational divide, thereby accelerating their application for patients suffering from PN."

Journal • Review • Neuroblastoma • Oncology • Pain • Peripheral Neuropathic Pain • Solid Tumor • CASP3 • CASP4 • CASP8 • GSDMC • GSDME • NLRP3

Avelumab plus axitinib in patients with advanced gastrointestinal stromal tumor. (PubMed, Eur J Cancer) - "The results of the largest trial on the combination of targeted therapy and immunotherapy in pretreated GIST show the promising efficacy of this novel therapeutic approach in a subset of patients."

Journal • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

SWOG S1931 (PROBE): Phase III randomized trial of immune checkpoint inhibitor (ICI) combination regimen with or without cytoreductive nephrectomy (CN) in advanced renal cancer. (ASCO-GU 2022) - P3 | "CARMENA trial demonstrated no change in overall survival with addition of nephrectomy to sunitinib therapy... Eligible patients with primary tumor and metastases are treated with one of the FDA approved ICI based combinations: ipililumab and nivolumab, axitinib and pembrolizumab, or axitinib and avelumab. Cabozantinib + nivolumab and lenvatinib + pembrolizumab combinations are being added into the next amendment...The study hypothesis is that CN will result in improvement in OS outcomes in advanced synchronous RCC post-initial systemic immune checkpoint based combination therapy. With a sample size of 302 eligible, randomized participants (151 per arm) and a one-sided alpha = 0.025, the study has 85% power to detect a 47% improvement in median survival (HR = 0.68; 1/0.68 = 1.47)"

Checkpoint inhibition • Clinical • P3 data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Real-world effectiveness and safety of first-line (1L) avelumab + axitinib (ave + axi) in patients with advanced renal cell carcinoma (aRCC): Final analysis of the prospective AVION study. (ASCO-GU 2026) - P | "Clinical Trial Registry Number: NCT04941768. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

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

A phase II open-label trial of avelumab plus axitinib in previously treated non-small-cell lung cancer or treatment-naïve, cisplatin-ineligible urothelial cancer. (PubMed, ESMO Open) - P2 | "In previously treated patients with advanced/metastatic NSCLC, ORR appeared to be superior to anti-PD-L1 or anti-programmed cell death protein 1 monotherapy, irrespective of PD-L1 status, whereas in untreated, cisplatin-ineligible patients with advanced/metastatic UC, ORR was lower than expected, potentially limited by small patient numbers."

IO biomarker • Journal • P2 data • Tumor mutational burden • Genito-urinary Cancer • Immune Modulation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD8 • TMB

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma. (PubMed, ESMO Open) - P3 | "Avelumab plus axitinib continues to show improved efficacy versus sunitinib and a tolerable safety profile overall and across IMDC risk groups. The OS trend favors avelumab plus axitinib versus sunitinib, but data remain immature; follow-up is ongoing."

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