Palbociclib + Sasanlimab for Kidney Cancer

Overseen By Wanda A Bell-Farrell

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP3A inducers, Corticosteroids, Herbal supplements

Disqualifiers: Autoimmune disease, Hepatitis B, Lung disease, others

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

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

Compensation: Varies

Number of Visits: 7

Duration: Up to 2 years

100 Participants Needed

Trial Summary

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

The trial requires participants to stop taking medications that are strong inhibitors or inducers of CYP3A (a liver enzyme) at least 21 days before starting the study. Herbal supplements must also be stopped 14 days before the trial begins. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug combination Palbociclib and Sasanlimab for kidney cancer?

While there is no direct data on Palbociclib and Sasanlimab for kidney cancer, similar drug combinations involving immune checkpoint inhibitors and tyrosine kinase inhibitors have shown improved outcomes in kidney cancer, with better survival rates and disease control. ^{1 2 3 4 5}

How is the drug combination of Palbociclib and Sasanlimab unique for kidney cancer?

The combination of Palbociclib and Sasanlimab is unique for kidney cancer as it involves a novel approach by combining a cell cycle inhibitor (Palbociclib) with an immunotherapy agent (Sasanlimab), potentially offering a new mechanism of action compared to existing treatments that primarily focus on targeting specific pathways like tyrosine kinase or mTOR. ^{2 3 4 6 7}

What is the purpose of this trial?

Background: Kidney cancer is the 12th leading cause of cancer-related death in the United States. Some kidney tumors do not respond well to current treatments. Better treatments are needed. Objective: To test a pair of drugs (sasanlimab and palbociclib) in people with kidney cancers. Eligibility: People aged 18 years and older with kidney cancer; specifically, clear cell renal cell carcinoma (ccRCC) or papillary renal cell carcinoma (pRCC). Design: Participants will be screened. They will have a physical exam with blood tests. They will have an imaging scan and a test of their heart function. They may have a biopsy; that is, a sample of tissue will be cut from the tumor. Participants will be treated in 28-day cycles for up to 2 years. Palbociclib is a pill taken by mouth. Participants will take this drug once a day for 21 days during each 28-day treatment cycle. They will write down the dates and times they take these pills in a diary. Sasanlimab is an injection under the skin. Participants will receive this injection on the first day of each treatment cycle. Imaging scans and blood tests will be repeated throughout the treatment. Tumor biopsies may be repeated up to 3 times; these biopsies are optional. Participants will have follow-up visits every month for 3 months after treatment ends. They will continue to have imaging scans every 3 months; these scans may be done close to home. The results can be sent to researchers. Participants will remain in the study up to 6 years.

Research Team

Ramaprasad Srinivasan

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults with advanced kidney cancer, either clear cell renal cell carcinoma (ccRCC) after checkpoint inhibitor therapy and possibly VEGF antagonist treatment, or papillary renal cell carcinoma (pRCC), which may be untreated. Participants need at least one measurable tumor lesion, good physical condition, adequate blood counts and organ function. They must agree to use effective contraception and not breastfeed during the trial.

Inclusion Criteria

Your kidneys and liver are working well, and you do not have certain viral infections. If you have brain metastasis, you must have completed treatment at least 4 weeks ago with no signs of progression.

My kidney cancer is confirmed as clear cell (ccRCC) or papillary (pRCC).

Your blood counts need to be within normal range, with a minimum number of white blood cells, red blood cells, and platelets.

Exclusion Criteria

I have had cancer other than kidney cancer in the last 2 years.

I have had a bone marrow or organ transplant in the past.

I have or had hepatitis B.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive palbociclib orally for 21 days and sasanlimab injection on the first day of each 28-day cycle, repeated for up to 2 years

Up to 2 years

Monthly visits for drug administration and monitoring

Follow-up

Participants have follow-up visits every month for 3 months after treatment ends, with imaging scans every 3 months

3 months

3 visits (in-person), imaging scans every 3 months

Long-term follow-up

Participants continue to have imaging scans every 3 months and are monitored for up to 6 years

Up to 6 years

Imaging scans every 3 months

Treatment Details

Interventions

• Palbociclib
• Sasanlimab

Trial Overview The trial is testing a combination of two drugs: Sasanlimab (an injection) given once each cycle, and Palbociclib (a pill) taken daily for 21 days in each 28-day cycle. The study aims to evaluate their effectiveness in treating kidney cancers over cycles lasting up to two years with follow-ups extending up to six years.

Participant Groups

Group I: 2/Phase II Experimental Treatment 2 Interventions

Sasanlimab and palbociclib at the dose determined in Phase I (RP2D)

Group II: 1/ Phase I Experimental Treatment 2 Interventions

Sasanlimab and deescalating doses of palbociclib

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

Approved in United States as Ibrance for:

• HR-positive, HER2-negative advanced or metastatic breast cancer

Approved in European Union as Ibrance for:

• HR-positive, HER2-negative locally advanced or metastatic breast cancer

Approved in Canada as Ibrance for:

• HR-positive, HER2-negative advanced or metastatic breast cancer

Approved in Japan as Ibrance for:

• HR-positive, HER2-negative advanced or recurrent breast cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Combination therapies using immune checkpoint inhibitors, such as axitinib plus pembrolizumab, have shown improved outcomes compared to traditional sequential monotherapy in patients with metastatic renal cell carcinoma.

Phase III trials indicate that these combination regimens significantly enhance both progression-free survival and overall survival, addressing the issue of drug resistance seen with single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib combination and the paradigm change in the treatment of advanced renal cell carcinoma. Spisarová, M., Melichar, B., Vitásková, D., et al.[2021]

Recent advancements in the treatment of metastatic kidney cancer include the approval of several drugs targeting the vascular endothelial growth factor pathway, such as sorafenib and sunitinib, which have shown efficacy particularly in patients with good- or intermediate-risk profiles and clear cell histology.

The development of effective treatment plans should consider not only drug therapies but also individual patient factors, surgical options, and emerging investigational therapies, emphasizing the importance of personalized treatment strategies based on data from pivotal trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy of kidney cancer: keeping the art around the algorithms. Fishman, MN.[2017]

In a study of 143 patients with advanced renal cell carcinoma (RCC), over 50% of patients remained on pazopanib therapy for nearly 4 months, demonstrating high persistence and compliance across both treatment-naïve and previously treated groups.

Younger age and higher comorbidity were identified as strong predictors of better persistence and compliance with pazopanib treatment, suggesting that these factors may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence and compliance with pazopanib in patients with advanced renal cell carcinoma within a U.S. administrative claims database. Hackshaw, MD., Nagar, SP., Parks, DC., et al.[2023]

Recent clinical trials have led to significant advancements in the treatment of metastatic renal cell carcinoma, particularly with the introduction of targeted therapies like bevacizumab, sunitinib, and newer agents such as axitinib and tivozanib.

Understanding the mechanisms of disease and drug resistance has opened up new targets for treatment, suggesting that the therapeutic landscape for kidney cancer is evolving rapidly with the potential for more effective interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapies in metastatic renal cell carcinoma: overview of the past year. Gross-Goupil, M., Massard, C., Ravaud, A.[2021]

The treatment landscape for renal cell carcinoma (RCC) has significantly improved over the past two decades, with the introduction of targeted therapies leading to a response rate of 30%-40% and an 80% benefit rate for patients, compared to only 5%-10% with older treatments.

The emergence of immuno-oncology therapies, particularly immune checkpoint inhibitors, has further enhanced treatment efficacy, achieving approximately 60% response rates and 90% disease control rates in metastatic RCC, paving the way for personalized medicine approaches tailored to individual tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Therapeutic Landscape of Renal Cell Carcinoma: From the Dark Age to the Golden Age. Huang, JJ., Hsieh, JJ.[2022]

Nivolumab, an anti-PD-1 antibody, shows promising effects in the treatment of advanced renal cancer, indicating its potential as an effective immunotherapy option.

The manuscript highlights the role of nivolumab in harnessing the immune system to target and combat renal cancer, suggesting a new avenue for treatment in this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nivolumab (Anti-PD-1 antibody; ONO-4538/BMS-936558) in renal cancer]. Ozono, S.[2018]

Palomid 529, a novel dual inhibitor of mTORC1/2, demonstrated significant anti-cancer effects by inducing cell death and inhibiting proliferation in renal cell carcinoma (RCC) cells, both in vitro and in vivo using a mouse model.

The effectiveness of Palomid 529 was enhanced when combined with BRD4 inhibitors, suggesting that targeting BRD4 could overcome resistance and improve treatment outcomes for RCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bromodomain-Containing Protein 4 (BRD4) Inhibition Sensitizes Palomid 529-Induced Anti-Renal Cell Carcinoma Cell Activity in Vitro and in Vivo. Xing, ZY., Wang, Y., Cheng, L., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib combination and the paradigm change in the treatment of advanced renal cell carcinoma. [2021]

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

Targeted therapy of kidney cancer: keeping the art around the algorithms. [2017]

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

Persistence and compliance with pazopanib in patients with advanced renal cell carcinoma within a U.S. administrative claims database. [2023]

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

Targeted therapies in metastatic renal cell carcinoma: overview of the past year. [2021]

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

The Therapeutic Landscape of Renal Cell Carcinoma: From the Dark Age to the Golden Age. [2022]

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

[Nivolumab (Anti-PD-1 antibody; ONO-4538/BMS-936558) in renal cancer]. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Bromodomain-Containing Protein 4 (BRD4) Inhibition Sensitizes Palomid 529-Induced Anti-Renal Cell Carcinoma Cell Activity in Vitro and in Vivo. [2019]