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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, sasanlimab and palbociclib, to determine their effectiveness in treating kidney cancer, specifically clear cell and papillary types. Kidney cancer poses significant challenges, and some treatments do not work well for everyone. Individuals with these types of kidney cancer, who have undergone certain treatments or have a measurable tumor, might be suitable candidates. Participants will take palbociclib pills and receive sasanlimab injections in cycles over two years, with close monitoring. The trial aims to discover a more effective treatment for those struggling with current options. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial group, offering participants a chance to contribute to potentially groundbreaking advancements in kidney cancer treatment.

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.

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

Researchers are investigating a combination of two drugs, palbociclib and sasanlimab, to treat kidney cancer. Early lab studies have shown promise for these drugs when used together.

Palbociclib, already approved for some types of breast cancer, has a well-understood safety profile in humans. It is generally well-tolerated but can cause side effects like a decrease in white blood cells, increasing the risk of infections.

Sasanlimab is still under study to determine its safety and effectiveness. It is designed to help the immune system fight cancer. Although detailed safety information on sasanlimab is limited, ongoing trials are closely monitoring for any side effects.

Early-phase trials primarily focus on safety, ensuring that any serious side effects are identified and addressed. Participants should discuss potential risks and benefits with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard care for kidney cancer that often involves surgery, targeted therapy, or immunotherapy, the combination of Palbociclib and Sasanlimab offers a new approach by potentially enhancing the body's immune response against cancer cells. Sasanlimab is an immune checkpoint inhibitor which helps to unleash the immune system, while Palbociclib is a CDK4/6 inhibitor that disrupts the cancer cell cycle, preventing them from multiplying. This dual-action approach not only targets the cancer cells directly but also boosts the immune system's ability to fight the disease, which could lead to improved outcomes for patients. Researchers are excited about this treatment because it represents a novel and potentially more effective strategy in tackling kidney cancer compared to existing options.

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

Research has shown that palbociclib might slow the growth of kidney cancer cells by blocking proteins that aid cancer cell growth. Sasanlimab, in contrast, strengthens the immune system, enabling it to attack cancer cells more effectively. In this trial, participants will receive a combination of palbociclib and sasanlimab. Although these results are promising, researchers are still studying the combination to determine its effectiveness specifically for kidney cancer. Early findings suggest that these treatments together could offer a new approach for tumors unresponsive to current therapies. ^{1 2 3 6 7}

Who Is on the Research Team?

Ramaprasad Srinivasan

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05665361

NCT05665361 | Palbociclib and Sasanlimab for the ... Objective: To test a pair of drugs (sasanlimab and palbociclib) in people with kidney cancers. Eligibility: People aged 18 years and older with kidney ...

2. kcrs.kidneycan.org kcrs.kidneycan.org/wp-content/uploads/2024/07/66_Gabriela_Bravo_Montenegro.pdf

A Phase I/II Study of Palbociclib and Sasanlimab for ... combination of bevacizumab and erlotinib. • Preclinical data suggest that inhibitors of CDK 4/6 might be active in kidney cancer and these agents might act.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05665361?cond=Papillary%20renal%20cell%20carcinoma%20OR%20%22chromophil%20carcinoma%20of%20kidney%22%20OR%20%22%20chromophil%20carcinoma%20of%20the%20kidney%22%20OR%20%22%20chromophil%20renal%20cell%20carcinoma%22%20OR%20%22%20HPRCC%22%20OR%20%22%20papillary%20(chromophil)%20renal%20cell%20carcinoma%22%20OR%20%22%20papillary%20kidney%20carcinoma%22%20OR%20%22%20papillary%20renal%20cell%20adenocarcinoma%22%20OR%20%22%20papillary%20renal%20cell%20cancer%22%20OR%20%22%20renal%20cell%20carcinoma,%20papillary,%20type%201%22%20OR%20%22%20sporadic%20papillary%20renal%20cell%20carcinoma%22&aggFilters=status:not%20rec&viewType=Table&rank=5

Palbociclib and Sasanlimab for the Treatment of Advanced ... Data from nonclinical studies indicate that palbociclib may have cytostatic effects on tumor cells. Sasanlimab is an investigational humanized immunoglobulin G ...

4. withpower.com withpower.com/trial/phase-2-kidney-neoplasms-7-2023-8783d

NKT2152 + Palbociclib + Sasanlimab for Kidney Cancer Nivolumab, when combined with ipilimumab, significantly improves overall survival rates in previously untreated advanced renal cell carcinoma (RCC), achieving ...

5. clinconnect.io clinconnect.io/trials/NCT07123090

A Phase 2 Study of Sasanlimab, Palbociclib and Axitinib The goal of this research study is to evaluate how well and safely the study drugs sasanlimab, palbociclib, and axitinib work for treatment of participants ...

6. dana-farber.org dana-farber.org/clinical-trials/25-258

A Phase 2 study of sasanlimab, palbociclib and axitinib in ... The goal of this research study is to evaluate how well and safely the study drugs sasanlimab, palbociclib, and axitinib work for treatment of participants ...

7. sigma.larvol.com sigma.larvol.com/product.php?e1=563542&tab=newstrac&page=2

sasanlimab (PF-06801591) News Secondary outcomes include additional efficacy end points and safety ... Enrollment open: Palbociclib and Sasanlimab for the Treatment of Advanced Clear Cell ...