Tivozanib + Nivolumab for Advanced Kidney Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: CYP3A inducers, Corticosteroids
Disqualifiers: Uncontrolled hypertension, Autoimmune disorders, HIV, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?To learn if giving tivozanib in combination with nivolumab can help to control advanced nccRCC.
Will I have to stop taking my current medications?
If you have received previous systemic therapy, you will need to stop and wait for a 'washout period' (time without taking certain medications) of 5 half-lives or 21 days, whichever is shorter. The protocol does not specify other medication restrictions, but you should discuss your current medications with the study team.
What data supports the effectiveness of the drug combination Tivozanib and Nivolumab for advanced kidney cancer?
Research shows that Nivolumab, when used with other drugs, improves survival and response rates in advanced kidney cancer. The combination of Nivolumab with other similar drugs has shown better outcomes compared to some standard treatments, suggesting potential benefits for this combination as well.
12345Is the combination of Tivozanib and Nivolumab safe for humans?
The combination of Tivozanib and Nivolumab has been studied in patients with advanced kidney cancer, showing a favorable safety profile with minimal off-target toxicities (unintended side effects).
678910How is the drug combination of Tivozanib and Nivolumab unique for advanced kidney cancer?
The combination of Tivozanib and Nivolumab is unique because it pairs a highly selective VEGFR inhibitor (Tivozanib) with an immune checkpoint inhibitor (Nivolumab), potentially offering improved progression-free survival and overall survival for patients with advanced kidney cancer compared to other treatments. This combination leverages both targeted therapy and immunotherapy, which is a novel approach in this context.
24111213Eligibility Criteria
Adults with advanced non-clear cell renal cell carcinoma, who have adequate organ function and no more than one prior systemic therapy. They must not be pregnant or breastfeeding, agree to use contraception, and cannot have uncontrolled hypertension or a history of severe allergic reactions to similar drugs.Inclusion Criteria
I can care for myself but may not be able to do heavy physical work.
I am 18 years old or older.
I've had only one type of systemic therapy for my cancer, which could include immunotherapy or targeted therapy.
+13 more
Exclusion Criteria
You have an autoimmune disorder, except for some specific conditions like vitiligo, alopecia, stable hypothyroidism, or certain chronic skin conditions that don't need strong medication.
Has evidence of any other medical conditions, psychiatric condition, physical examination or laboratory findings that may interfere with the planned treatment, affect subject compliance or place the subject at high risk from treatment-related complications in the opinion of the local principal investigator (PI)
I have previously been treated with nivolumab.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive tivozanib tablets daily for 21 days and nivolumab intravenously every 4 weeks
4 weeks per cycle
1 visit (in-person) every 4 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing the combination of Tivozanib (a tyrosine kinase inhibitor) and Nivolumab (an immunotherapy agent) in patients with advanced kidney cancer that's not the usual 'clear cell' type. The goal is to see if this combo can control the disease better.
1Treatment groups
Experimental Treatment
Group I: Combination Tivozanib and NivolumabExperimental Treatment2 Interventions
Nivolumab by vein over about 60 minutes every 4 weeks (Day 1 of each cycle). Tivozanib tablets by mouth 1 time every day for 21 days (Days 1-21 of each cycle), and then no tablets on Days 22-28 of each cycle.
Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:
🇺🇸 Approved in United States as Opdivo for:
- Advanced or metastatic gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Esophageal squamous cell carcinoma
🇪🇺 Approved in European Union as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
🇨🇦 Approved in Canada as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
🇨🇭 Approved in Switzerland as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
AVEO Pharmaceuticals, Inc.Industry Sponsor
References
Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma. [2022]Nivolumab is effective for advanced renal cell carcinoma; however, reports are limited wherein nivolumab is combined with sequential therapy of angiogenesis inhibitors and metastasectomy.
[Immunotherapy for renal cell carcinoma - current status]. [2019]Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially changed during the last 2 years due to approval of the immune-checkpoint inhibitor Nivolumab (Opdivo®) and new multikinase inhibitors (Cabozantinib, Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted therapy. CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs. 19.7 month; hazard ratio 0.73; p = 0.0006) and response rate (26 % vs. 5 %) as well as a favorable toxicity profile compared with Everolimus. Currently, numerous combinations with PD-1/PD-L1 inhibitors are compared to Sunitinib as first line treatment of mRCC. Out of these CheckMate 214, a randomized phase-3 trial is the first to demonstrate a significant higher objective response rate (42 % vs. 27 %, p < 0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo + Ipi has been not yet reached (28.2 - NR); Hazard ratio 0.63) for the combination of Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk patients. Furthermore, CheckMate 214 shows better side effect profile and quality of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib. However, a considerable increase of immune related adverse events is associated with the immune combination therapy. Another randomized trial demonstrates improved progression-free survival for the combination of the PD-L1 inhibitor Atezolizumab and the VEGF antibody Bevacizumab in patients with PD-L1 positive tumors; this was found in all IMDC risk groups. Further phase-3 trials with "new" VEGFR-TKIs (Axitinib, Cabozantinib, Lenvatinib) and PD-1/PD-L1 inhibitor combinations are ongoing.In conclusion, the PD-1 immune checkpoint inhibitor Nivolumab will remain a standard treatment for patients with metastatic renal cell carcinoma after prior VEGF targeted therapy. Nivolumab in combination with Ipilimumab will become a standard 1st line option for patients with intermediate and high risk profile according to IMDC. Further data are required regarding PD-1/PD-L1 inhibitors in combination with Bevacizumab and VEGFR-TKIs, respectively, including overall survival and side effect profile.
Efficacy and Safety of Nivolumab for Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. [2022]To assess the efficacy and safety of nivolumab for advanced renal cell carcinoma (RCC) via meta-analysis.
The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibitor-based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care. [2022]The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. PATIENT SUMMARY: New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.
Frontline immunotherapy treatment with nivolumab and ipilimumab in metastatic renal cell cancer: a new standard of care. [2020]Nivolumab is a programmed death 1 (PD-1) inhibitor currently approved as second-line treatment for advanced renal cell carcinomas (RCC) after failure of standard antiangiogenic treatment. Motzer et al. have recently published in the New England Journal of Medicine the findings of CheckMate 214 trial, using nivolumab and ipilimumab, a cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor, versus sunitinib in previously untreated advanced RCC. The combination demonstrated a higher 18-month overall survival rate of 75% versus 60%, and a higher objective response rate of 42% versus 27%, for the combination in favor over sunitinib monotherapy. These results herald the rapidly changing role of immune checkpoint inhibitor therapy as first-line treatment for metastatic RCC.
Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]Recently, many agents and combinations for metastatic and advanced renal cell carcinoma have been approved. This study aims to highlight the comprehensive differences in adverse events (AEs) between cabozantinib (CAB) plus nivolumab (NIVO) and ipilimumab (IPI) plus NIVO based on a real-world big dataset.
Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real-world results from an expanded access programme. [2022]To report the safety and efficacy results of patients enrolled in the Italian Nivolumab Renal Cell Cancer Expanded Access Programme.
Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. [2022]The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known.
TiNivo: safety and efficacy of tivozanib-nivolumab combination therapy in patients with metastatic renal cell carcinoma. [2021]Treatment with tivozanib, a highly selective and potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, has demonstrated single-agent efficacy in advanced renal cell carcinoma (RCC) along with minimal off-target toxicities and a favorable adverse event (AE) profile. We report final results from TiNivo, a phase Ib/II study of tivozanib combined with nivolumab.
Real-world Data of Nivolumab for Patients With Advanced Renal Cell Carcinoma in the Netherlands: An Analysis of Toxicity, Efficacy, and Predictive Markers. [2021]Nivolumab, a programmed death 1 inhibitor, has been approved as second-line treatment for advanced renal cell carcinoma (RCC) in Europe since 2016. We investigated the toxicity and efficacy of nivolumab as well as potential predictive biomarkers in the Dutch population.
Final Data Analysis Supports Tivozanib as Superior Treatment for Patients With RCC. [2021]Tivozanib (Fotivda) significantly improved progression-free survival (PFS), compared with sorafenib (Nexavar), in patients with highly relapsed or refractory metastatic renal cell carcinoma (RCC), according to results from the phase 3 TIVO-3 trial presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program.
Tivozanib: First Global Approval. [2018]Tivozanib (Fotivda®) is an oral, potent and highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor that has been approved in the EU, Iceland and Norway for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mammalian target of rapamycin (mTOR) pathway inhibitor-naive following disease progression after one prior treatment with cytokine therapy for advanced RCC. Tivozanib is at various stages of development in other countries for advanced RCC and advanced solid tumours. This article summarizes the milestones in the development of tivozanib leading to this first global approval in Europe for the treatment of adults with advanced RCC.
Tivozanib for the treatment of advanced renal cell carcinoma. [2022]Renal cell carcinoma (RCC) accounts for 2.4% of cancers, with clear cell kidney cancer being the most common histologic subtype. Despite recent therapeutic advances, the prognosis for patients with advanced disease remains poor, with a 5-year survival rate of only 13.9% reported in the United States. Tivozanib is a novel inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1, -2, and -3 and has recently been approved by the US FDA for use in patients with relapsed or recurrent advanced RCC following two or more prior systemic therapies.