Immune Checkpoint Inhibitors + Axitinib for Kidney Cancer

Not currently recruiting at 95 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatment combinations for kidney cancer that cannot be removed by surgery or has spread to other parts of the body (metastatic clear-cell renal cell carcinoma). The study aims to determine if a new drug, tobemstomig (an experimental treatment), is effective and safe when combined with existing medications like axitinib, either alone or with another new drug, tiragolumab. The trial will compare these combinations to an established treatment using pembrolizumab and axitinib. Individuals who have never received treatment for this type of kidney cancer and can confirm their diagnosis might be suitable participants. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies tested the combination of tobemstomig and axitinib for safety in various cancer types. Researchers aimed to determine the optimal dose and assess patient tolerance. Although detailed safety information is unavailable, the treatment has reached Phase 2, indicating that early tests deemed it safe enough for broader trials.

The combination of tobemstomig with tiragolumab and axitinib has also undergone safety studies in other cancers, such as bladder cancer. The objective was to evaluate its safety and compare it with other treatments.

Axitinib alone has received FDA approval for kidney cancer, confirming its safety and effectiveness for that use.

In summary, early research suggests these treatments are generally safe for further testing, but specific side effects and their frequency remain under study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for kidney cancer because they offer novel approaches compared to the usual therapies like sunitinib and cabozantinib. Tobemstomig, a part of the trial, is noteworthy because it specifically targets unique immune pathways, potentially enhancing the body's ability to fight cancer cells. When combined with axitinib, it could improve outcomes by working on both the immune system and cancer cell growth. Additionally, the combination of tobemstomig and tiragolumab aims to boost the immune response even further by blocking different checkpoints, offering a fresh strategy in cancer treatment. These innovations could lead to more effective therapies with potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

Research shows that immune checkpoint inhibitors, like tobemstomig, can help treat advanced kidney cancer by enabling the immune system to identify and attack cancer cells. In this trial, participants in Arm A will receive a combination of tobemstomig with axitinib, a drug that blocks the blood supply to tumors, potentially enhancing treatment effectiveness. Arm B will explore the addition of tiragolumab, which also boosts the immune system, possibly improving results further. Although researchers are still learning about tobemstomig, similar treatments have shown promise in clinical trials. For example, participants in the Control Arm will receive pembrolizumab, a well-known checkpoint inhibitor, combined with axitinib, which has proven effective for kidney cancer, offering hope for these new combinations. ^{1 2 4 5 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-LaRoche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/rcc/a-study-of-immune-checkpoint-inhibitor-combinations-wit-47221.html

Clinical study | Renal Cell Carcinoma RO7247669 | ForPati... This study will evaluate the safety of tobemstomig (RO7247669) in combination with axitinib alone or with tiragolumab (anti-TIGIT) and axitinib as compared ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05805501

NCT05805501 | A Study of Immune Checkpoint Inhibitor ... This study will evaluate the safety of tobemstomig (RO7247669) in combination with axitinib alone or with tiragolumab (anti-TIGIT) and axitinib as compared ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10777977/

Emerging Immunotherapy Approaches for Advanced Clear ... Immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 and CTLA-4 inhibitors have demonstrated clinical efficacy as monotherapies and in ...

4. withpower.com withpower.com/trial/phase-2-carcinoma-2-2023-62f67

Immune Checkpoint Inhibitors + Axitinib for Kidney Cancer In the phase 3 KEYNOTE-426 trial involving 861 patients, the combination of pembrolizumab and axitinib significantly improved overall survival and progression- ...

5. mdpi.com mdpi.com/2077-0383/13/19/5738

Novel Immune Checkpoint Inhibitor Targets in Advanced or ... NCT05805501 is a randomized, open-label, three-arm phase II trial that evaluates the efficacy, safety, and pharmacokinetics of the anti-PD-1 and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04140500

NCT04140500 | Dose Escalation Study of a PD1-LAG3 ... This study aims to establish the maximum tolerated dose (MTD) and/or define the recommended phase 2 dose (RP2D) based on the safety, tolerability, ...