scholarly journals Phase Ib Study of Atezolizumab Plus Interferon-α with or without Bevacizumab in Patients with Metastatic Renal Cell Carcinoma and Other Solid Tumors

2021 ◽  
Vol 28 (6) ◽  
pp. 5466-5479
Author(s):  
Christian U. Blank ◽  
Deborah J. Wong ◽  
Thai H. Ho ◽  
Todd M. Bauer ◽  
Carrie B. Lee ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Solid Tumors ◽  
Renal Cell ◽  
Checkpoint Inhibitor ◽  
Interferon Α ◽  
Clinical Activity ◽  
Phase Ib ◽  
Treatment Naïve ◽  
Previously Treated

This Phase Ib study combined programmed death-ligand 1 inhibitor, atezolizumab, with other immunomodulatory agents in locally advanced and metastatic solid tumors. Arms B-D evaluated atezolizumab plus interferon-α, with/without vascular endothelial growth factor inhibitor, bevacizumab, in renal cell carcinoma (RCC) and other solid tumors. Arm B predominantly recruited patients with previously treated RCC or melanoma to receive atezolizumab plus interferon α-2b. Arm C investigated atezolizumab plus polyethylene glycol (PEG)-interferon α-2a in previously treated RCC. Arm D evaluated atezolizumab plus PEG-interferon α-2a and bevacizumab. Primary objectives were safety and tolerability; secondary objectives included clinical activity. Combination therapy was well tolerated, with safety profiles consistent with known risks of individual agents. The most frequent treatment-related toxicities were fatigue, chills, and pyrexia. The objective response rate (ORR) in arm B was 20.0% overall and 17.8% in patients with previously treated checkpoint inhibitor–naive RCC (n = 45). No responses were reported in arm C. The highest ORR in arm D was 46.7% in patients with treatment-naive RCC (n = 15). Data showed preliminary clinical activity and acceptable tolerability of atezolizumab plus interferon α-2b in patients with previously treated checkpoint inhibitor–naive RCC and of atezolizumab plus PEG-interferon α-2a and bevacizumab in patients with treatment-naive RCC.

Clinical activity of PD1/PDL1 inhibitors in metastatic non-clear cell renal cell carcinoma (nccRCC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 482-482 ◽  
Author(s):  
Raphael Brandao Moreira ◽  
Rana R. McKay ◽  
Wanling Xie ◽  
Daniel Yick Chin Heng ◽  
Guillermo de Velasco ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Clinical Activity ◽  
Significant Activity ◽  
Cell Renal Cell Carcinoma ◽  
Treatment Naïve ◽  
Retrospective Multicenter Study

482 Background: PD1/PDL1 inhibitors have shown significant activity in the treatment of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC), but their activity in nccRCC is poorly characterized. Methods: We conducted a retrospective multicenter study of pts with metastatic nccRCC treated with PD1/PDL1 inhibitors. Baseline clinical parameters, overall response rate (ORR) by RECIST, time-to-treatment failure (TTF), and overall survival (OS) were summarized. Results: We identified 40 pts across 8 academic institutions. Fourteen (35%) had papillary histology, 10 (25%) chromophobe, 3 (8%) translocation, and 7 (18%) unclassified. Six (16%) had ccRCC with a sarcomatoid component > 30%. 20% had International Metastatic RCC Database Consortium (IMDC) favorable-risk disease, 60% intermediate, and 20% poor-risk. Ten (25%) were treatment-naïve and the majority received PD1/PDL1 monotherapy (n=30, 75%), while the remaining received a combination of PD1/PDL1 with anti-VEGF(R) or anti-CTLA4 therapy. ORR for the total cohort was 18% and 10% for PD1/PDL1 monotherapy pts (Table). With a median follow-up of 5.6 months, the overall median TTF was 4.7 months (2.9-15.9) and six-month OS was 81% (60-91%). Conclusions: PD1/PDL1 blockade resulted in some activity in pts with various nccRCC histologies. In the absence of available clinical trials, this data may support the use of PD1/PDL1 blocking agents in pts with nccRCC. [Table: see text]

Efficacy of VEGFR-TKI plus immune checkpoint inhibitor (ICI) in metastatic renal cell carcinoma (mRCC) patients with favorable IMDC prognosis.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 318-318
Author(s):  
Chiara Ciccarese ◽  
Roberto Iacovelli ◽  
Emilio Bria ◽  
Giovanni Schinzari ◽  
Ernesto Rossi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Meta Analysis ◽  
Favorable Prognosis ◽  
Treatment Naïve

318 Background: Combinations of a PD-1/PD-L1 immune checkpoint inhibitor (ICI) with a VEGFR-TKI as front-line/treatment-naïve therapy significantly improve the outcome of metastatic renal cell carcinoma (mRCC) patients. The benefit of these combinations is well evident in IMDC intermediate- and poor-risk population, while it is unclear in the subgroup of mRCC patients with favorable prognosis. We performed a meta-analysis with the aim to evaluate whether the addition of ICIs to VEGFR-TKIs is able to improve the outcome compared to VEGFR-TKIs alone in mRCC patients with favorable IMDC prognosis. Methods: This meta-analysis searched MEDLINE/PubMed, the Cochrane Library and ASCO Meeting abstracts for phase II or III randomized clinical trials (RCTs) testing the combination of VEGFR-TKI+ICI in mRCC. Data extraction was conducted according to the PRISMA statement. The hazard ratios (HRs) for PFS and OS with the relative 95% CIs were extracted from each study. Summary HRs was calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies. Results: Three RCTs were selected for the final analysis, with a total of 605 patients (306 treated with VEGFR-TKI+ICI combinations and 299 who received sunitinib in the control arms). The combination of VEGFR-TKI+ICI improved PFS compared to sunitinib, with a 30% reduction of the risk of progression (fixed-effect, HR=0.70; p = 0.003). However, VEGFR-TKI+ICI combinations did not significantly prolong OS (fixed-effect; HR = 0.94; 95% CI 0.62–1.43; p = 0.77). Conclusions: Our analysis demonstrates a PFS benefit without an OS advantage for VEGFR-TKI+ICI combinations as first-line therapy for mRCC patients with favourable prognosis according to IMDC. Longer follow-up is required to definitely confirm the best therapy for treatment-naïve mRCC patients with favorable prognosis. [Table: see text]

Avelumab plus axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma: Phase 3 study (JAVELIN Renal 101).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4594-TPS4594 ◽  
Author(s):  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
James M. G. Larkin ◽  
Georg A. Bjarnason ◽  
Gwenaelle Gravis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Advanced Renal Cell Carcinoma ◽  
Clinical Activity ◽  
Line Treatment ◽  
First Line ◽  
Phase 3 ◽  
Treatment Naïve ◽  
Ecog Ps

TPS4594 Background: The combination of a checkpoint inhibitor with an anti-VEGF agent is a promising treatment strategy for advanced renal cell carcinoma (aRCC). Avelumab is a fully human IgG1 anti–PD-L1 antibody with clinical activity in aRCC and other tumor types (eg, Apolo et al. ASCO 2016; Gulley et al. ECC 2015). Axitinib is an anti-VEGF receptor tyrosine kinase inhibitor approved for second-line treatment of aRCC (Rini et al. Lancet 2011) that has also shown clinical activity as a first-line (1L) therapy (Hutson et al. Lancet Oncol 2013). In an ongoing phase 1b study in treatment-naïve patients (pts) with aRCC, avelumab + axitinib administered at standard monotherapy doses showed a tolerable safety profile and encouraging antitumor activity (Larkin et al. ESMO 2016). JAVELIN Renal 101 is a randomized, multicenter, phase 3 study (NCT02684006) comparing avelumab + axitinib vs sunitinib in pts with treatment-naïve aRCC. Methods: The primary objective is to demonstrate superiority of avelumab + axitinib vs sunitinib in prolonging progression-free survival (PFS) in the 1L treatment of pts with aRCC. Eligibility criteria include: aRCC with a clear cell component, ECOG PS ≤1, no prior systemic therapy for advanced disease, and measurable disease per RECIST v1.1. Approximately 583 pts will be randomized 1:1 and stratified based on ECOG PS (0 vs 1) and region (US vs Canada/Europe vs rest of the world). Pts receive either avelumab 10 mg/kg IV Q2W + axitinib 5 mg orally BID continuously (cycle length 6 weeks) or sunitinib 50 mg orally once daily for 4 weeks followed by 2 weeks off. Treatment is discontinued for unacceptable toxicity or if any other criteria for withdrawal are met. Pts may continue treatment beyond progression (RECIST v1.1) if investigator-assessed clinical benefit is achieved and treatment is well tolerated. PFS is assessed by blinded central review. Secondary efficacy assessments include overall survival, objective response, disease control, duration of response, and time to response. Safety, PK, and biomarker analyses will also be performed. The trial is currently active at 103 sites across 12 countries and as of Feb 2017, more than 40% of patients have been enrolled. Clinical trial information: NCT02684006.

Phase I study of PTK787/ZK222584 (PTK/ZK) and RAD001 for patients with advanced solid tumors and dose expansion in renal cell carcinoma patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5039-5039 ◽  
Author(s):  
J. C. Speca ◽  
A. L. Mears ◽  
P. A. Creel ◽  
S. E. Yenser ◽  
J. C. Bendell ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Solid Tumors ◽  
Renal Cell ◽  
Clinical Activity ◽  
Pharmacokinetic Studies ◽  
Advanced Solid Tumors ◽  
Mtor Inhibition ◽  
Orally Active

5039 Background: PTK/ZK is an orally active tyrosine kinase inhibitor that blocks all known VEGF receptors. RAD001 is an orally active macrolide which selectively inhibits mTOR. Combination therapy with VEGFR and mTOR inhibition may have additive efficacy in several tumor types, particularly renal cell carcinoma (RCC). Materials and Methods: A phase I/II study of PTK/ZK and RAD001 was performed in patients with advanced solid tumors to determine the maximum tolerated dose (MTD), safety and tolerability. Patients were given escalating daily doses of PTK/ZK in combination with RAD001 (see table ) in 28-day cycles. Patients were assessed for adverse events every 2 weeks and tumor response every 2 cycles. A dose expansion cohort of 20 patients with metastatic RCC is ongoing to further evaluate safety and preliminary efficacy. Results: To date, 27 patients have received a total of 136 cycles. The dose escalation phase included 14 patients and 3 dose levels; dose-limiting toxicities included grade 3 diarrhea and hypertriglyceridemia (14%); asthenia, fatigue and mucositis (7%). Pharmacokinetic studies are pending. A MTD of PTK/ZK 1,000 mg and RAD001 5 mg daily was determined and studied in an expanded cohort of RCC patients. Prior therapy with a VEGF inhibitor was allowed. To date, 13 evaluable RCC patients demonstrate 2 (15%) partial responses and 8 (62%) with stable disease > 3 months; median TTP is 6 months. Conclusions: PTK/ZK and RAD001 combination is well-tolerated and demonstrates clinical activity in patients with RCC despite prior exposure to VEGF inhibition. An MTD of 1,000 mg daily of PTK/ZK and 5 mg daily of RAD001 is the recommended dose for Phase II/III testing. [Table: see text] No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document