Savolitinib + Durvalumab vs. Sunitinib for Kidney Cancer

(SAMETA Trial)

Recruiting at 140 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

148 Participants Needed

Trial Summary

What is the purpose of this trial?

A clinical trial to compare the effectiveness of savolitinib plus durvalumab versus sunitinib in MET-driven (hepatocyte growth factor receptor), unresectable and locally advanced or metastatic PRCC (Papillary Renal Cell Carcinoma).

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.

What data supports the effectiveness of the drug Savolitinib + Durvalumab for kidney cancer?

Sunitinib, a component of the treatment being compared, has shown effectiveness in treating advanced renal cell cancer by targeting pathways crucial for tumor growth. Additionally, combining durvalumab with other similar antibodies has shown potential in improving treatment efficacy for advanced kidney cancer. ^{1 2 3 4 5}

What is the safety profile of Sunitinib for kidney cancer?

Sunitinib, used for treating kidney cancer, has a distinct set of side effects that need careful monitoring. Common side effects include fatigue, diarrhea, high blood pressure, and changes in the thyroid, with some patients experiencing more severe issues like low blood cell counts and skin problems. Managing these side effects is important to ensure patients can continue treatment effectively. ^{1 6 7 8 9}

How does the drug combination of Savolitinib and Durvalumab differ from Sunitinib for kidney cancer?

The combination of Savolitinib and Durvalumab is unique because it combines a MET inhibitor (Savolitinib) with an immune checkpoint inhibitor (Durvalumab), potentially offering a novel approach by targeting both tumor growth pathways and enhancing the immune response, unlike Sunitinib, which is a tyrosine kinase inhibitor focusing on blocking specific growth factor receptors. ^{1 3 10 11 12}

Research Team

Toni Choueiri, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Sunitinib: a newly approved small-molecule inhibitor of angiogenesis. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Sunitinib for advanced renal cell cancer. [2023]

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

Sequential therapy with sorafenib and sunitinib in renal cell carcinoma. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Case report of kidney cancer from JOUM 2010]. [2011]

5. United States 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. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

[Management of sunitinib-associated adverse events]. [2018]

7. Canada pubmed.ncbi.nlm.nih.gov

Sunitinib therapy for metastatic renal cell carcinoma: recommendations for management of side effects. [2021]

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

Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of sunitinib in patients from Latin America: subanalysis of an expanded access trial in metastatic renal cell carcinoma. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Sunitinib in the treatment of metastatic renal cell carcinoma. [2020]

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

Sequential sorafenib and sunitinib for renal cell carcinoma. [2018]

12. France pubmed.ncbi.nlm.nih.gov

Sunitinib: new drug. For some gastrointestinal stromal tumours. [2009]