A5017490262- Renal cell carcinoma treatment
- Cancer Immunotherapy and Biomarkers
- Bladder and Urothelial Cancer Treatments
- Renal and related cancers
- Peptidase Inhibition and Analysis
- Cancer Genomics and Diagnostics
- Urinary and Genital Oncology Studies
- Advanced Breast Cancer Therapies
- Adenosine and Purinergic Signaling
- Economic and Financial Impacts of Cancer
- Pancreatic and Hepatic Oncology Research
- Cancer Diagnosis and Treatment
- Multiple and Secondary Primary Cancers
- Epigenetics and DNA Methylation
- Adrenal and Paraganglionic Tumors
- Glioma Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Cancer, Hypoxia, and Metabolism
- Testicular diseases and treatments
- Ferroptosis and cancer prognosis
- Lung Cancer Research Studies
- Sarcoma Diagnosis and Treatment
- Prostate Cancer Treatment and Research
- Metastasis and carcinoma case studies
- Neuroblastoma Research and Treatments
The University of Texas MD Anderson Cancer Center
2016-2025
Fox Chase Cancer Center
2024
Spanish Oncology Genitourinary Group
2019-2021
University of Pennsylvania
2013
Baylor College of Medicine
2010
Albert Einstein College of Medicine
1998
The efficacy and safety of nivolumab plus cabozantinib as compared with those sunitinib in the treatment previously untreated advanced renal-cell carcinoma are not known.
Abstract Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for should not impede antitumor immunity. Understanding the mechanisms critical to overcome this challenge, but pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients arthritis-irAE, and unmask a prominent...
•With 44.0 months of median follow-up for OS, long-term efficacy outcomes with NIVO + CABO over SUN were maintained.•Median OS (95% CI) in ITT patients: 49.5 (40.3 months-NE) vs 35.5 (29.2-42.3 months) SUN.•Survival favoured across intermediate, poor and combined intermediate/poor IMDC risk subgroups.•Objective responses durable CABO; response rates higher versus regardless group.•No new safety signals emerged additional either treatment arm. BackgroundNivolumab plus cabozantinib (NIVO CABO)...
362 Background: N+C demonstrated superior progression-free survival (PFS), overall (OS), and objective response rate (ORR) vs S in patients (pts) with previously untreated aRCC the primary analysis of phase 3 CheckMate 9ER trial (18.1 mo median follow-up). maintained efficacy benefits 44.0 follow-up. Here, we report updated intent-to-treat (ITT) pts by International Metastatic RCC Database Consortium (IMDC) risk, safety extended Methods: Pts were randomized to N 240 mg every 2 weeks + C 40...
439 Background: N+C showed significant benefits vs S in progression-free survival (PFS), overall (OS), and objective response rate (ORR) for patients (pts) with previously untreated aRCC from the phase 3 CheckMate 9ER trial ( N Engl J Med 2021; 384:829–41). We report final results a long-term follow-up (min, >5 y), including updated efficacy intent-to-treat (ITT) pts by International Metastatic RCC Database Consortium (IMDC) risk, safety. Methods: Pts were randomized to receive first-line...
Current treatment guidelines for immune-mediated diarrhea and colitis (IMDC) recommend steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) refractory cases. We aimed to compare the efficacy of these two SITs their impact on cancer outcomes.We performed a two-center, retrospective observational cohort study patients with IMDC who received following from 2016 2020. Patients' demographic, clinical, overall survival data were...
Background In this multicenter, single‐arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder upper tract carcinoma variant histology (BUTCVH), adrenal tumors, platinum‐refractory germ cell penile carcinoma, prostate cancer (NCT03333616). Methods Patients malignancies no prior immune checkpoint inhibitor exposure were enrolled. received at 3 mg/kg 1 intravenously every weeks for 4 doses,...
308 Background: First-line NIVO+CABO met primary and secondary efficacy endpoints by improving progression-free survival (PFS; HR 0.51, P < 0.0001), overall (OS; 0.60, = 0.0010), objective response rate (ORR; 55.7% vs 27.1%; 0.0001) SUN in patients (pts) with aRCC CheckMate 9ER (Choueiri et al. ESMO 2020). Efficacy benefits were consistent across prespecified subgroups including IMDC risk group, regardless of tumor PD-L1 expression (database lock for analysis, March 30, Updated analyses...
The accumulation of immune-suppressive myeloid cells is a critical determinant resistance to anti–programmed death-1 (PD-1) therapy in advanced clear cell renal carcinoma (ccRCC). In preclinical models, the tyrosine kinase inhibitor sitravatinib enhanced responses anti–PD-1 by modulating cells. We conducted phase 1-2 trial choose an optimal dose combined with fixed nivolumab 42 immunotherapy-naïve patients ccRCC refractory prior antiangiogenic therapies. combination demonstrated no...
Methylthioadenosine phosphorylase, an essential enzyme for the adenine salvage pathway, is often deficient (MTAPdef) in tumors with 9p21 loss and hypothetically renders susceptible to synthetic lethality by antifolates targeting de novo purine synthesis. Here we report our single arm phase II trial (NCT02693717) that assesses pemetrexed MTAPdef urothelial carcinoma (UC) primary endpoint of overall response rate (ORR). Three 7 enrolled patients show (ORR 43%). Furthermore, a historic cohort...
603 Background: First-line nivolumab plus cabozantinib (N+C) demonstrated superiority over sunitinib (S) with 25.4 mo minimum follow-up (median, 32.9 mo) in patients (pts) aRCC the CheckMate 9ER trial. Here, we report survival, response per blinded independent central review (BICR), and safety after 3 y all randomized pts by IMDC risk score. Methods: Pts were 1:1 (stratified score, tumor PD-L1 expression, region) to N 240 mg flat dose IV Q2W + C 40 PO QD vs SUN 50 for 4 wk (6-wk cycles)...
Abstract Sitravatinib is an immunomodulatory tyrosine kinase inhibitor that can augment responses when combined with programmed death-1 inhibitors such as nivolumab. We report a single-arm, interventional, phase 2 study of neoadjuvant sitravatinib in combination nivolumab patients locally advanced clear cell renal carcinoma (ccRCC) prior to curative nephrectomy (NCT03680521). The primary endpoint was objective response rate (ORR) surgery null hypothesis ORR = 5% and the alternative set at...
Abstract We conducted a phase I trial to determine the optimal dose of triplet therapy with tyrosine kinase inhibitor sitravatinib plus nivolumab ipilimumab in 22 previously untreated patients advanced clear cell renal carcinoma. The primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control (DCR), duration (DOR), progression-free survival (PFS), overall (OS), 1-year probability, and pharmacokinetics. Sitravatinib 35 mg daily 3 mg/kg 1 resulted high...
Background Nivolumab plus ipilimumab (nivo/ipi) is a standard of care first-line (1 L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC), but its role in metastatic, non-ccRCC has not been fully defined. We report single-institution experience nivo/ipi non-ccRCC. Methods Between November 2017 and February 2024, 55 received at MD Anderson Cancer Center. The tumor response was assessed by blinded radiologists using RECIST v1.1. overall rate (ORR), progression-free...
558 Background: Nivo/ipi is a standard of care first-line (1L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC) but its role in variant histology RCC (vhRCC) has not been fully defined. Methods: We report single-institution experience nivo/ipi to treat 55 vhRCC between Nov. 2017 and Feb. 2024 at MD Anderson Cancer Center. Tumor response was measured by blinded radiologists using RECIST v1.1. Descriptive statistics the Kaplan-Meier method were used. Results:...
We have examined the roles of p85/ p110α and hVPS34 phosphatidylinositol (PI) 3′-kinases in cellular signaling using inhibitory isoform-specific antibodies. raised anti-hVPS34 anti-p110α antibodies that specifically inhibit recombinant p110α, respectively, vitro. used to study processes are sensitive low-dose wortmannin. The had distinct effects on actin cytoskeleton; microinjection blocked insulin-stimulated ruffling, whereas no effect. also different vesicular trafficking. Microinjection...