Savolitinib + Durvalumab vs. Sunitinib for Kidney Cancer

(SAMETA Trial)

Not currently recruiting at 173 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: MET inhibitors, Durvalumab, Sunitinib

Disqualifiers: Liver cirrhosis, Cardiac disease, Active infection, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 28 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of a combination of two drugs, savolitinib and durvalumab (an immunotherapy drug), against sunitinib for treating MET-driven papillary renal cell carcinoma (PRCC), a specific type of kidney cancer. Researchers seek to determine which treatment works better for individuals with advanced or metastatic cancer that cannot be surgically removed. Participants should have this specific type of kidney cancer and must not have received certain cancer treatments previously. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had prior exposure to MET inhibitors, Durvalumab, or Sunitinib.

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

Studies have shown that the combination of savolitinib and durvalumab is generally well-tolerated. Earlier research indicated that patients with a type of kidney cancer responded well to this combination, with manageable side effects. While some side effects occurred, they were not severe for most people.

For durvalumab alone, research shows it has a manageable safety profile. Some patients experienced more serious side effects, such as sudden kidney problems and reactions during infusion, but these were uncommon.

Savolitinib and durvalumab are being tested together for kidney cancer, and both have shown promise in other studies. The trial is in an advanced stage, indicating some evidence of safety in humans.

Sunitinib, already approved by the FDA for treating kidney cancer, has a well-known safety profile. Most people tolerate it well, though it can cause side effects like tiredness and diarrhea.

Overall, each treatment in this trial has demonstrated a certain level of safety in other studies. It's important to weigh the potential benefits against any risks when considering participation. Always consult your doctor to determine if it is right for you. ^{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 new approaches compared to traditional therapies like Sunitinib, a standard treatment. Unlike Sunitinib, which targets multiple pathways in cancer cells, Savolitinib with Durvalumab zeroes in on MET-driven tumors and boosts the immune system's ability to fight cancer. Savolitinib is a selective MET inhibitor, providing a targeted approach, while Durvalumab is an immune checkpoint inhibitor that enhances the body's natural defense against cancer. In contrast, Durvalumab alone, as another experimental arm, focuses on harnessing the immune system without the additional targeting provided by Savolitinib, potentially offering a less aggressive option with immune-based treatment.

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

Research has shown that savolitinib, a MET inhibitor, may help treat MET-driven papillary renal cell carcinoma (PRCC), a specific type of kidney cancer. Early findings suggest it blocks pathways that promote cancer cell growth. In this trial, some participants will receive a combination of savolitinib and durvalumab, an immune checkpoint inhibitor. Durvalumab has proven effective in treating other kidney cancers, with studies showing it can shrink tumors and reduce the risk of death by 25%. Combining savolitinib and durvalumab might enhance treatment by attacking the cancer in different ways. However, previous trials like CALYPSO have produced mixed results, indicating the need for further research. Another group of participants will receive sunitinib, a standard treatment known to slow cancer growth. ^{1 6 7 8 9}

Who Is on the Research Team?

Toni Choueiri, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with MET-driven, unresectable and locally advanced or metastatic Papillary Renal Cell Carcinoma (PRCC). Participants must have measurable lesions, good organ/bone marrow function, a life expectancy of at least 12 weeks, no prior cancer treatments in the metastatic setting or exposure to the drugs being tested. They should not have serious liver disease, brain metastases unless stable and asymptomatic, significant heart issues within the past 6 months, active infections like HIV/TB/HBV/HCV or autoimmune/inflammatory disorders.

Inclusion Criteria

I haven't had any cancer treatment in the metastatic stage or been treated with MET inhibitors, Durvalumab, or Sunitinib.

My PRCC is confirmed to be MET-driven by a specific lab test.

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

I have a history of serious liver disease or cirrhosis.

I have or had an autoimmune or inflammatory disorder.

My brain or spinal tumors are stable and I've been symptom-free for at least 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either savolitinib plus durvalumab, sunitinib, or durvalumab monotherapy until progression or unacceptable toxicity

Approximately 28 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 28 months

Open-label extension (optional)

Participants in the durvalumab monotherapy arm may switch to receive savolitinib in combination with durvalumab upon progression

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Savolitinib
• Sunitinib

Trial Overview

The study compares savolitinib combined with durvalumab against sunitinib alone and durvalumab alone in patients with PRCC that's driven by MET gene changes. The goal is to see which combination works better for this type of kidney cancer that can't be removed by surgery.

How Is the Trial Designed?

Group I: Arm C Experimental Treatment 1 Intervention

durvalumab 1500mg

Group II: Arm A Experimental Treatment 2 Interventions

savolitinib 600mg plus durvalumab 1500mg

Group III: Arm B Active Control 1 Intervention

sunitinib 50mg

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a study of 90 patients with renal cell carcinoma, sequential treatment with sorafenib followed by sunitinib resulted in a median overall survival of 135 weeks, compared to 82 weeks for the reverse sequence, indicating that the order of administration may impact survival outcomes.

Both treatment sequences were well tolerated, with no increase in severe toxicity (grade 3-4), suggesting that sequential administration of these tyrosine kinase inhibitors is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential sorafenib and sunitinib for renal cell carcinoma. Sablin, MP., Negrier, S., Ravaud, A., et al.[2018]

Sunitinib has demonstrated superiority as a first-line therapy for intermediate-risk metastatic clear cell renal carcinoma based on three clinical cases.

Bevacizumab combined with interferon showed better safety profiles, highlighting the need for more high-level evidence for neo-adjuvant treatments in kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Case report of kidney cancer from JOUM 2010]. Neuzillet, Y., Guy, L., Long, JA., et al.[2011]

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

Sunitinib is an effective treatment for metastatic renal cell carcinoma (mRCC) in Japan, showing high therapeutic response and prolonged survival, but it has a distinct toxicity profile that requires careful monitoring.

The most common severe side effect of sunitinib is myelotoxicity, particularly thrombocytopenia, affecting 73% of patients, with 36.8% experiencing grade 3 or higher toxicity, indicating the need for dose adjustments and individualized treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of sunitinib-associated adverse events]. Kanda, H., Masui, S., Yamada, Y., et al.[2018]

In a study of 49 patients with advanced renal cell carcinoma, those who received sorafenib followed by sunitinib (Group A) experienced a longer median duration of stable disease (20 weeks) compared to those who received sunitinib followed by sorafenib (Group B) with only 9.5 weeks.

Patients in Group A also had a longer median time to disease progression (78 weeks) compared to Group B (37 weeks), suggesting that the sequence of treatment may impact the effectiveness of these tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy with sorafenib and sunitinib in renal cell carcinoma. Dudek, AZ., Zolnierek, J., Dham, A., et al.[2022]

Sunitinib is an effective first-line treatment for metastatic renal cell cancer (mRCC), showing superiority over interferon alpha in a phase III trial, but it comes with significant side effects like diarrhea, hypertension, and fatigue.

An alternative dosing schedule of sunitinib (2 weeks on, 1 week off) may offer similar efficacy with better tolerability, and ongoing trials are exploring its use alongside newer immune checkpoint inhibitors in mRCC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib in the treatment of metastatic renal cell carcinoma. Schmid, TA., Gore, ME.[2020]

Citations

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pmc.ncbi.nlm.nih.gov

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Health determinants vary according to geographic region and may affect the outcomes of patients with metastatic renal cell carcinoma (mRCC) treated during ...

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Recent phase 3 results with peri-operative durvalumab show a 25% reduction in the risk of death compared to standard of care. Methods: RADIO is ...

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Combination of durvalumab with platin-based chemotherapy, especially cisplatin, showed promising activity in UTUC, with the occurrence of complete responses.

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MEDI4736 Combinations in Metastatic Renal Cell Carcinoma

This study is being carried out to see if the drugs MEDI4736, Savolitinib and Tremelimumab can be used alone or in combination to reduce the size of tumours ...

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Durvalumab Plus Chemo May be Promising Neoadjuvant ...

Durvalumab (Imfinzi) plus chemotherapy was safe and yielded encouraging residual disease outcomes, according to data from the phase 2 iNDUCT trial.