Immune Checkpoint Inhibitors + Axitinib for Kidney Cancer

Recruiting at 82 trial locations

Overseen By Reference Study ID Number: BO43936 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: CYP3A4/5 inhibitors, Immunosuppressants

Disqualifiers: Pregnancy, CNS metastases, Hypertension, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 21-day cycles, ongoing

199 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use strong CYP3A4/5 inhibitors or inducers, or systemic immunosuppressive medications within 2 weeks before starting the study. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of immune checkpoint inhibitors and axitinib for kidney cancer?

Research shows that the combination of axitinib and pembrolizumab has a 73% response rate in patients with advanced kidney cancer, and it is considered a standard first-line treatment for this condition, improving survival compared to other treatments. ^{1 2 3 4 5}

Is the combination of immune checkpoint inhibitors and axitinib safe for treating kidney cancer?

The combination of axitinib and immune checkpoint inhibitors like pembrolizumab has been studied for safety in treating advanced kidney cancer. Common side effects include diarrhea, liver issues, fatigue, and heart-related problems, which require careful management to ensure patient safety. ^{2 3 4 6 7}

What makes the drug combination of Axitinib, Pembrolizumab, RO7247669, and Tiragolumab unique for kidney cancer?

This drug combination is unique because it includes a bispecific antibody (RO7247669) that targets both PD-1 and LAG-3, potentially enhancing the immune response against kidney cancer, alongside the established combination of Axitinib and Pembrolizumab, which is already a standard treatment for advanced renal cell carcinoma. ^{2 3 5 8 9}

What is the purpose of this trial?

This trial is testing a new drug combination for patients with advanced kidney cancer that can't be removed by surgery. The treatment aims to stop the cancer by blocking its blood supply and boosting the immune system. The combination of atezolizumab and bevacizumab has shown promise in treating advanced kidney cancer by helping patients live longer without the disease worsening.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-LaRoche

Eligibility Criteria

This trial is for adults with advanced kidney cancer that hasn't been treated yet. They should be able to perform daily activities with ease (ECOG PS of 0 or 1) and have a certain level of risk based on the IMDC score. Participants must not have HIV, hepatitis B/C, serious infections recently, autoimmune diseases, significant bleeding events or other cancers in the last two years. Pregnant women and those who can't take oral medication are excluded.

Inclusion Criteria

My kidney cancer is classified as intermediate or poor risk.

I have at least one tumor that can be measured.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I cannot swallow pills or have a condition that affects how my body absorbs nutrients.

I have a history of congenital QT syndrome.

I need IV fluids, nutrition, or tube feeding due to GI issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tobemstomig with axitinib, tobemstomig with tiragolumab and axitinib, or pembrolizumab with axitinib

21-day cycles, ongoing

IV administration every 3 weeks, oral medication twice daily

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Axitinib
• Pembrolizumab
• RO7247669
• Tiragolumab

Trial Overview The study tests combinations of immune checkpoint inhibitors (Tiragolumab, Tobemstomig) with Axitinib against Pembrolizumab plus Axitinib in patients with untreated renal cell carcinoma. It aims to compare their effectiveness and safety while also studying how these drugs behave in the body over time.

Participant Groups

Group I: Arm B (Tobemstomig + Tiragolumab + Axitinib) Experimental Treatment 3 Interventions

Participants will receive IV tobemstomig followed by IV tiragolumab Q3W on Day 1 of 21-day cycle. Participants will also receive axitinib PO BID.

Group II: Arm A (Tobemstomig + Axitinib) Experimental Treatment 2 Interventions

Participants will receive intravenous (IV) tobemstomig every three weeks (Q3W) on Day 1 of each 21-day cycle. Participants will also receive oral (PO) axitinib twice daily (BID).

Group III: Control Arm (Pembrolizumab + Axitinib) Active Control 2 Interventions

Participants will receive IV pembrolizumab Q3W on Day 1 of each 21-day cycle. Participants will also receive axitinib PO BID.

Axitinib is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Inlyta for:

• Renal cell carcinoma

Approved in United States as Inlyta for:

• Advanced renal cell carcinoma

Approved in United Kingdom as Inlyta for:

• Advanced renal cell carcinoma

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

In a subgroup analysis of 94 Japanese patients with metastatic renal cell carcinoma, the combination of pembrolizumab and axitinib showed improved overall survival and progression-free survival compared to sunitinib, consistent with results from the larger global study.

The safety profile was also favorable, with fewer grade ≥3 treatment-related adverse events in the pembrolizumab-axitinib group (70%) compared to sunitinib (78%), and no deaths from treatment-related adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. Tamada, S., Kondoh, C., Matsubara, N., et al.[2022]

The combination of axitinib and pembrolizumab shows a high response rate of 73% in patients with previously untreated advanced renal cell carcinoma, indicating strong efficacy for this treatment regimen.

This finding suggests that the dual approach of targeting both tumor growth and immune response may be effective in managing advanced kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

In a real-world study of 355 patients with advanced clear cell renal cell carcinoma, the combination of axitinib and pembrolizumab showed a best overall response rate of 47.9% and a one-year overall survival rate of 73.5%.

Treatment-related toxicity was the primary reason for dose adjustments, but over 80% of patients who experienced treatment management events were able to continue their therapy, suggesting that dose holds can be an effective strategy to manage side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Therapy Management and Outcomes of First-Line Axitinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma in the United States. Zakharia, Y., Thomaidou, D., Li, B., et al.[2022]

The combination of avelumab and axitinib showed promising antitumor activity in treatment-naive patients with advanced renal-cell carcinoma, with 58% of patients achieving confirmed objective responses in the study involving 55 participants.

The safety profile of the combination treatment was manageable, with adverse events similar to those seen with each drug alone, and the maximum tolerated dose was established as avelumab 10 mg/kg every 2 weeks and axitinib 5 mg twice daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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, TK., Larkin, J., Oya, M., et al.[2022]

Recent randomized trials have shown that the combination of pembrolizumab and axitinib significantly improves survival in patients with metastatic clear-cell renal cell carcinoma, establishing it as a new standard of care.

This treatment is recommended for all treatment-naïve patients, regardless of their risk group, according to updated guidelines from the European Association of Urology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma. Albiges, L., Powles, T., Staehler, M., et al.[2020]

Axitinib combined with immune checkpoint inhibitors (ICI) like pembrolizumab or avelumab is now approved for treating advanced renal cell carcinoma, but distinguishing between adverse events (AEs) caused by each treatment is crucial for optimizing therapy.

Experts identified specific AEs such as diarrhea, hepatic toxicity, fatigue, and cardiovascular issues that require unique management strategies when using axitinib-ICI combinations, emphasizing the need for careful clinical monitoring and tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. Grünwald, V., Voss, MH., Rini, BI., et al.[2021]

The combination of axitinib and pembrolizumab is tolerable and shows promising antitumor activity in patients with treatment-naive advanced renal cell carcinoma, with 73% of patients achieving an objective response.

In a study involving 52 patients, no unexpected toxicities were observed, although 65% experienced grade 3 or worse treatment-related adverse events, indicating that while the treatment is effective, it does carry some risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Atkins, MB., Plimack, ER., Puzanov, I., et al.[2023]

In the phase 3 KEYNOTE-426 trial involving 861 patients, the combination of pembrolizumab and axitinib significantly improved overall survival and progression-free survival compared to sunitinib for advanced renal cell carcinoma.

While both treatment groups showed similar health-related quality of life outcomes, the time to confirmed deterioration favored sunitinib, indicating that while pembrolizumab + axitinib is more effective in extending survival, it does not significantly enhance quality of life compared to sunitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life Analysis from KEYNOTE-426: Pembrolizumab plus Axitinib Versus Sunitinib for Advanced Renal Cell Carcinoma. Bedke, J., Rini, BI., Plimack, ER., et al.[2022]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Therapy Management and Outcomes of First-Line Axitinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma in the United States. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Individualised axitinib regimen for patients with metastatic renal cell carcinoma after treatment with checkpoint inhibitors: a multicentre, single-arm, phase 2 study. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life Analysis from KEYNOTE-426: Pembrolizumab plus Axitinib Versus Sunitinib for Advanced Renal Cell Carcinoma. [2022]