Savolitinib vs. Sunitinib for Kidney Cancer

Not currently recruiting at 63 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: CYP3A4 inducers, CYP1A2 inhibitors

Disqualifiers: Brain metastases, Active infections, Other cancers, 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

Compensation: Varies

Number of Visits: 6

Duration: 23-47 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new cancer drug, savolitinib, in treating MET-driven papillary renal cell carcinoma (PRCC), a specific type of kidney cancer. Researchers will compare savolitinib to sunitinib, an existing targeted therapy, to determine which is more effective and to identify any side effects. The trial seeks participants diagnosed with this type of cancer who have not previously received sunitinib or any MET inhibitors. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, including strong inducers or inhibitors of CYP3A4 and strong inhibitors of CYP1A2, at least 2 weeks before randomization. Herbal medications must be stopped 7 days before, and St John's wort 3 weeks before. If you are on any of these, you will need to stop them before participating.

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

Research has shown that savolitinib is generally well-tolerated by patients. In one study, savolitinib caused fewer serious side effects compared to sunitinib, a common treatment for certain kidney cancers. The study also found fewer instances where savolitinib's dosage required adjustment due to side effects.

Sunitinib, already approved by the FDA for treating kidney cancer, has a well-established safety profile. However, it can cause serious side effects in some patients.

Both treatments have been tested in many patients. While savolitinib may have fewer serious side effects, individual reactions to treatments can vary. It is crucial to discuss with a doctor what to expect and determine the best option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney cancer?

Researchers are excited about Savolitinib as a treatment for kidney cancer because it targets a specific pathway involved in tumor growth, known as the MET receptor pathway. Unlike standard treatments like Sunitinib, which target multiple pathways, Savolitinib offers a more focused approach, potentially leading to fewer side effects and a better safety profile. This precise targeting could mean improved effectiveness for patients with MET-driven kidney cancer, making it a promising option for those who may not respond well to existing therapies.

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

This trial will compare the effectiveness of savolitinib and sunitinib for treating kidney cancer. Research has shown that savolitinib, a MET inhibitor, may effectively treat a specific kind of kidney cancer known as MET-driven papillary renal cell carcinoma (PRCC). One study found that 27% of patients responded well to savolitinib, compared to only 7% who responded to sunitinib, a treatment currently in use. Savolitinib also caused fewer serious side effects and required fewer dose adjustments. Although the average survival time was slightly lower with savolitinib compared to other treatments, its effectiveness in treating MET-driven PRCC makes it a promising option. Overall, savolitinib could be a better choice for people with this specific type of kidney cancer. Participants in this trial will receive either savolitinib or sunitinib to evaluate their effectiveness and safety. ^{1 3 4 6 7}

Who Is on the Research Team?

Toni K Choueiri, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with MET-driven, advanced Papillary Renal Cell Carcinoma (PRCC) that can't be surgically removed. It's open to those who haven't had treatment or have had previous systemic therapy. Participants need good blood, kidney, heart, and liver function and a high level of physical ability. They must not have other active cancers or recent cancer treatments, untreated brain metastases, or conditions affecting the heart's rhythm.

Inclusion Criteria

I have or haven't had systemic therapy for advanced PRCC.

My blood, kidney, heart, and liver functions are all within normal ranges.

I can carry out normal activities with minimal symptoms.

Exclusion Criteria

I haven't had major surgery in the last 4 weeks or minor surgery in the last week.

My brain cancer has not been treated yet.

I have not had treatment for any invasive cancer in the last 5 years, nor do I have any other active cancers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either savolitinib or sunitinib to assess efficacy and safety in treating MET-driven PRCC

23-47 weeks

RECIST tumour assessments every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Savolitinib
• Sunitinib

Trial Overview The study compares Savolitinib (a new anti-cancer medication) with Sunitinib (an established treatment), in patients with PRCC to see which is more effective and what side effects they might cause. Patients will be randomly assigned to receive either drug and monitored for results.

How Is the Trial Designed?

Group I: Savolitinib Experimental Treatment 1 Intervention

See: intervention description

Group II: Sunitinib Active Control 1 Intervention

See: intervention description

Savolitinib is already approved in China for the following indications:

Approved in China as Orpathys for:

• Non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations

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

Hutchison Medipharma Limited

Industry Sponsor

Trials

104

Recruited

14,000+

Dr. Weiguo Su

Hutchison Medipharma Limited

Chief Executive Officer since 2022

PhD in Chemistry from Harvard University, BSc in Chemistry from Fudan University

Dr. Karen Atkin

Hutchison Medipharma Limited

Chief Medical Officer since 2023

MD from Harvard Medical School

Hutchinson MediPharma (HMP)

Collaborator

Trials

1

Recruited

60+

Published Research Related to This Trial

Sunitinib has been established as the standard first-line treatment for advanced renal cell carcinoma, based on results from a large-scale, long-term Phase III trial.

Conventional treatments like nephrectomy followed by IL-2 or IFN-alpha often do not provide long-term survival benefits, highlighting the importance of targeted therapies like sunitinib in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib (SUTENT) for the treatment of metastatic renal cell carcinoma. Hutson, TE.[2018]

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 a similar safety profile in patients undergoing nephrectomy for kidney cancer, whether used in the adjuvant setting or for metastatic disease, based on data from phase III trials including CARMENA and SURTIME.

Effective management of sunitinib's adverse effects is crucial, particularly in the adjuvant setting, where maintaining dose intensity and exposure can impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of sunitinib in patients with renal cell carcinoma following nephrectomy. Heraudet, L., Domblides, C., Daste, A., et al.[2022]

Sunitinib, an oral tyrosine kinase inhibitor, has shown significant antitumor activity and improved progression-free survival in patients with renal cell carcinoma, based on phase II and III clinical trials.

Understanding the unique side effects of sunitinib is crucial for effective patient education, enabling better anticipation and management of these therapy-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma. Schwandt, A., Wood, LS., Rini, B., et al.[2022]

In a Phase III trial involving treatment-naive patients with metastatic renal cell carcinoma (mRCC), sunitinib significantly improved progression-free survival compared to IFN-α, demonstrating its efficacy as a first-line treatment.

Sunitinib is effective even in challenging cases, such as patients with non-clear cell histology or those who are refractory to other treatments, and while it has common side effects like fatigue and hypertension, these may also indicate better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of sunitinib in renal cell carcinoma: where are we now? Czarnecka, AM., Szczylik, C., Rini, B.[2018]

Sunitinib malate is a multi-kinase inhibitor approved for treating advanced renal cell carcinoma and other specific tumors, showing modest antitumor activity in ovarian cancer based on Phase I and II trials.

The drug has an acceptable safety profile, but further research is needed to better understand its toxicity and to explore combination therapies for enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. Leone Roberti Maggiore, U., Valenzano Menada, M., Venturini, PL., et al.[2018]

In a study of 41 patients with advanced renal cell carcinoma and renal impairment, both sunitinib and sorafenib showed similar efficacy in terms of progression-free survival (6.6 months for sunitinib vs 5.8 months for sorafenib) and overall survival (65.9 months vs 58.0 months).

However, sunitinib was associated with a higher frequency of grade 3 or higher adverse events compared to sorafenib, indicating a need for careful monitoring of side effects, especially in patients with prior kidney surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era. Takayama, T., Kubo, T., Yamazaki, M., et al.[2020]

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 treatment for advanced metastatic renal cell carcinoma (mRCC), showing a significant improvement in progression-free survival compared to interferon-alpha, with 11 months for sunitinib versus 5 months for interferon-alpha in a Phase III study.

In Phase II trials, sunitinib demonstrated a partial response rate of 40% and 34% as a second-line therapy for mRCC patients who did not respond to previous cytokine treatments, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib (Sutent): a novel agent for the treatment of metastatic renal cell carcinoma. Chouhan, JD., Zamarripa, DE., Lai, PH., et al.[2018]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2766797

Efficacy of Savolitinib vs Sunitinib in Patients With MET ... The ORR showed 9 of 33 (27%) patients (95% CI, 13.3-45.5) in the savolitinib group had a response, compared with 2 of 27 (7%) patients (95% CI, ...

2. urotoday.com urotoday.com/conference-highlights/asco-gu-2020/asco-gu-2020-kidney-cancer/119279-asco-gu-2020-overall-survival-results-for-durvalumab-and-savolitinib-in-metastatic-papillary-renal-cancer.html

Overall Survival Results for Durvalumab and Savolitinib in ... Savolitinib is a potent selective MET inhibitor that has been shown to have activity in patients with MET driven papillary renal cell carcinoma.1 In the ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32469384/

The SAVOIR Phase 3 Randomized Clinical Trial Savolitinib demonstrated encouraging efficacy vs sunitinib, with fewer grade 3 or higher AEs and dose modifications.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00767

Final Overall Survival Analysis of S1500 The median OS was 19.9 months (95% CI, 11.2 to 40.8) with crizotinib and 11.7 months (95% CI, 6.7 to 29.5) with savolitinib. OS landmark ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36809050/

Phase II Study Investigating the Safety and Efficacy of ... The median overall survival was 14.1 months (95% CI, 7.3 to 30.7) in the treated population and 27.4 months (95% CI, 9.3 to not reached [NR]) in ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.22.01414

Phase II Study Investigating the Safety and Efficacy of ... The combination of savolitinib and durvalumab was tolerable and associated with high cRRs in the exploratory MET-driven subset.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03091192

Savolitinib vs. Sunitinib in MET-driven PRCC. The purpose of this study is to see if an investigational new anti-cancer medication, savolitinib, is effective in treating patients with MET-driven PRCC.