Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial

Choueiri, Toni K.; Larkin, James; Oya, Mototsugu; Thistlethwaite, Fiona; Martignoni, Marcella; Nathan, Paul; Powles, Thomas; McDermott, David F.; Robbins, Paul B.; Chism, David D.; Cho, Daniel; Atkins, Michael B.; Gordon, Michael; Gupta, Sumati; Uemura, Hirotsugu; Tomita, Yoshihiko; Compagnoni, Anna; Fowst, Camilla; Pietro, Alessandra di; Rini, Brian I.

doi:10.1016/s1470-2045(18)30107-4

Cited by 228 publications

(179 citation statements)

References 17 publications

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“…Simultaneous inhibition of the programmed death‐1 (PD‐1)/PD‐L1 immune checkpoint and VEGF/VEGFR signaling showed synergistic antitumor effects in preclinical models, leading to the hypothesis that treatment with a combination of these two drug classes might have clinical benefit above that of either drug alone. Preliminary data from a single‐arm phase 1b study of avelumab + axitinib in treatment‐naive patients with advanced RCC showed a manageable safety profile and encouraging antitumor activity, with an objective response rate (ORR) of 58% . The randomized phase 3 JAVELIN Renal 101 clinical trial of avelumab + axitinib vs sunitinib in previously untreated patients with advanced RCC demonstrated longer PFS (median, 13.8 vs 7.2 months; stratified hazard ratio [HR], 0.61; P < 0.001) and higher ORR (55.2% vs 25.5%) with the combination vs sunitinib in patients with PD‐L1+ tumors .…”

Section: Introductionmentioning

confidence: 99%

“…Preliminary data from a single-arm phase 1b study of avelumab + axitinib in treatment-naive patients with advanced RCC showed a manageable safety profile and encouraging antitumor activity, with an objective response rate (ORR) of 58%. 22 The randomized phase 3 JAVELIN Renal 101 clinical trial of avelumab + axitinib vs sunitinib in previously untreated patients with advanced RCC demonstrated longer PFS (median, 13.8 vs 7.2 months; stratified hazard ratio [HR], 0.61; P < 0.001) and higher ORR (55.2% vs 25.5%) with the combination vs sunitinib in patients with PD-L1+ tumors. 23 Different intrinsic demographic factors, such as genetic background, dietary habits, and medical environments (eg, diagnostic surveillance and available treatment options) may influence clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

et al. 2020

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The phase 3 JAVELIN Renal 101 trial of avelumab + axitinib vs sunitinib in patients with treatment‐naive advanced renal cell carcinoma (RCC) demonstrated significantly improved progression‐free survival (PFS) and higher objective response rate (ORR) with the combination vs sunitinib. Japanese patients enrolled in the study (N = 67) were randomized to receive avelumab + axitinib (N = 33) or sunitinib (N = 34); 67% vs 59% had PD‐L1+ tumors (≥1% of immune cells) and 6%/64%/27% vs 6%/82%/12% had International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable/intermediate/poor risk status. In patients who received avelumab + axitinib vs sunitinib, median PFS (95% confidence interval [CI]) was not estimable (8.1 months, not estimable) vs 11.2 months (1.6 months, not estimable) (hazard ratio [HR], 0.49; 95% CI, 0.152, 1.563) in patients with PD‐L1+ tumors and 16.6 months (8.1 months, not estimable) vs 11.2 months (4.2 months, not estimable) (HR, 0.66; 95% CI, 0.296, 1.464) in patients irrespective of PD‐L1 expression. Median overall survival (OS) has not been reached in either arm in patients with PD‐L1+ tumors and irrespective of PD‐L1 expression. ORR (95% CI) was 60.6% (42.1%, 77.1%) vs 17.6% (6.8%, 34.5%) in patients irrespective of PD‐L1 expression. Common treatment‐emergent adverse events (all grade; grade ≥3) in each arm were hand‐foot syndrome (64%; 9% vs 71%; 9%), hypertension (55%; 30% vs 44%; 18%), hypothyroidism (55%; 0% vs 24%; 0%), dysgeusia (21%; 0% vs 56%; 0%) and platelet count decreased (3%; 0% vs 65%; 32%). Avelumab + axitinib was efficacious and tolerable in treatment‐naive Japanese patients with advanced RCC, which is consistent with results in the overall population.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

et al. 2020

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“…Recent clinical trials for advanced RCC seemed to focus on combination therapy . They included combination regimens with two ICIs, such as nivolumab plus ipilimumab, and those with ICIs and angiogenesis inhibitors, such as pembrolizumab plus axitinib, and avelumab plus axitinib …”

Section: Biomarkers For Immune Checkpoint Therapymentioning

confidence: 99%

Current status of prognostic factors in patients with metastatic renal cell carcinoma

et al. 2019

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In recent years, the induction of novel agents, including molecular‐targeted agents and immune checkpoint inhibitors, have dramatically changed therapeutic options and their outcomes for metastatic renal cell carcinoma. Several prognostic models based on the data of patients with metastatic renal cell carcinoma treated with targeted agents or cytokine therapy have been useful in real clinical practice. Serum or peripheral blood markers related to inflammatory response have been reported to be associated with their prognosis or therapeutic efficacy. In addition to them, investigation for novel predictive factors that represent the efficacy of agents, the risk of adverse events and the prognosis are required for the advance of therapeutic strategies. The present review discusses the conventional prognostic models and clinical factors, and recent advances of the identification of some of the most promising molecules as novel biomarkers for metastatic renal cell carcinoma.

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“…IMmotion151 recently reported superior PFS with atezolizumab plus bevacizumab versus sunitinib in PD‐L1+ patients (coprimary endpoint) and in ITT patients (secondary endpoint); the data for analysis of OS in ITT patients (coprimary endpoint) are not yet mature . Early‐phase trials suggest promising efficacy with avelumab plus axitinib, nivolumab plus cabozantinib, pembrolizumab plus axitinib, and pembrolizumab plus lenvatinib . Results from phase III trials are expected beginning in late 2018, which will determine whether any of these combinations will be added to the RCC treatment armamentarium.…”

Section: Ongoing Studies Of Investigational First‐line Regimensmentioning

confidence: 99%

The Current and Evolving Landscape of First-Line Treatments for Advanced Renal Cell Carcinoma

Calvo¹,

Porta

Grünwald

et al. 2018

The Oncologist

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Vascular endothelial growth factor receptor tyrosine kinase inhibitors are approved by the U.S. Food and Drug Administration as first-line treatment options for advanced renal cell carcinoma; however, the treatment paradigm is rapidly evolving. The combination of nivolumab plus ipilimumab was recently approved for intermediate- and poor-risk patients, and other combination strategies and novel first-line agents will likely be introduced soon.

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Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial

Cited by 228 publications

References 17 publications

Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

Current status of prognostic factors in patients with metastatic renal cell carcinoma

The Current and Evolving Landscape of First-Line Treatments for Advanced Renal Cell Carcinoma

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