NKT2152 + Palbociclib + Sasanlimab for Kidney Cancer

No longer recruiting at 7 trial locations

Overseen By Joanna Dojillo, M.Sc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NiKang Therapeutics, Inc.

Must not be taking: HIF2α inhibitors, CDK 4/6 inhibitors

Disqualifiers: CNS metastases, Cardiovascular disease, HIV, others

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

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications for advanced kidney cancer that hasn't responded to previous treatments. Researchers aim to find the best dose and assess the safety and effectiveness of these new combinations against tumors. The trial includes two main groups: one testing NKT2152 (an experimental treatment) with palbociclib, and another adding sasanlimab (also known as PF-06801591) to the mix. It suits those with metastatic clear cell renal cell carcinoma who have tried at least one anti-VEGF/VEGFR treatment and one immune checkpoint inhibitor. Participants must also be able to swallow pills.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have previously been treated with NKT2152, palbociclib, or sasanlimab, you cannot participate in this trial.

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

Earlier studies have shown that NKT2152 produces promising results in patients with advanced clear cell renal cell carcinoma (ccRCC). Patients responded well to the treatment, and researchers are now testing it with two other drugs, palbociclib and sasanlimab.

Palbociclib is already approved for treating other types of cancer and is generally safe. Most people tolerate it well, though some might experience side effects like tiredness or low white blood cell counts. Sasanlimab has been tested with palbociclib for kidney cancer, showing similar side effects, but it remains under study.

This trial is in Phase 2, indicating some early information on safety, but more data is needed. Researchers aim to find the right dose and ensure safety when used with other drugs. This phase helps confirm that patients can handle the treatment and guides any necessary adjustments before further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments NKT2152, Palbociclib, and Sasanlimab for kidney cancer because they offer a fresh approach to tackling this disease. Unlike standard treatments like tyrosine kinase inhibitors and immune checkpoint inhibitors, these drugs work together to target cancer cells in a novel way. NKT2152 is particularly intriguing as it aims to inhibit tumor growth by affecting the cells' metabolism. When combined with Palbociclib, a known cell cycle inhibitor, and Sasanlimab, an immune checkpoint inhibitor, there's potential for a more comprehensive attack on kidney cancer cells. This combination could lead to improved outcomes for patients who don't respond well to existing therapies.

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

Research suggests that combining NKT2152 and palbociclib, which participants in this trial may receive in the Doublet combination arms, may effectively treat advanced kidney cancer. In previous studies, NKT2152 shrank tumors in 20% of patients with kidney cancer, with even better results in some groups. Palbociclib, when combined with other treatments, prevented cancer from worsening for a year in 88% of similar cases.

For participants in the Triplet combination arms, the addition of sasanlimab is under study. Research is ongoing, but sasanlimab is known to boost the immune system, potentially enhancing treatment effectiveness. Although limited data exist on using all three drugs together, each one individually shows promise for treating kidney cancer. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer (ccRCC) who've already tried at least one anti-VEGF/VEGFR therapy and one immune checkpoint inhibitor. Participants must be able to take oral meds, have a certain level of physical function (KPS score ≥70%), and measurable disease by RECIST 1.1 standards. Excluded are those with recent major heart issues, surgeries, HIV, active hepatitis B or C, recent radiation treatment, abnormal ECG readings, need for oxygen therapy due to hypoxia, brain metastases complications or history of autoimmune diseases.

Inclusion Criteria

Measurable disease per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

I can take pills by mouth.

I am mostly able to care for myself and carry out daily activities.

Exclusion Criteria

I have a history of lung scarring or fibrosis.

I haven't had major surgery in the last 3 months.

I have HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in

Dose escalation phase to evaluate safety, efficacy, and pharmacokinetics (PK) and determine recommended dose for expansion (RDE) of NKT2152 in combination with palbociclib and sasanlimab

4 weeks

Expansion

Evaluate safety, efficacy, and PK at the selected RDE and identify the RP2D for NKT2152 in combination with palbociclib and sasanlimab

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• NKT2152
• Palbociclib
• Sasanlimab

Trial Overview The study tests the safety and effectiveness of NKT2152 combined with palbociclib ('Doublet') and then adds sasanlimab ('Triplet') in patients with advanced kidney cancer post previous treatments. The Lead-in phase determines safe dosage levels while the Expansion phase evaluates these dosages further to find an optimal dose for future use.

How Is the Trial Designed?

Group I: Lead-in Triplet combination Experimental Treatment 3 Interventions

Lead-in Triplet assesses the safety of two doses of NKT2152 identified in the Doublet arm (RDE and RDE-1) by orally dosing ccRCC patients with NKT2152 in combination with palbociclib and sasanlimab

Group II: Lead-in Doublet combination Experimental Treatment 2 Interventions

Lead-in Doublet assesses safety of oral dosing NKT2152 at increasing dosage levels in combination with palbociclib to determine a recommended dose for expansion (RDE).

Group III: Expansion Triplet combination Experimental Treatment 3 Interventions

Subjects randomized to Arm 2 will receive the Triplet therapy (NKT2152 in combination with palbociclib and sasanlimab) to provide an assessment of anti-tumor activity and to determine the RP2D.

Group IV: Expansion Doublet combination Experimental Treatment 2 Interventions

Subjects randomized to Arm 1 will receive the Doublet combination (NKT2152 in combination with palbociclib) to provide an assessment of anti-tumor activity and to determine the RP2D.

Who Is Running the Clinical Trial?

NiKang Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

1,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

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]

Nivolumab, when combined with ipilimumab, significantly improves overall survival rates in previously untreated advanced renal cell carcinoma (RCC), achieving an 18-month survival rate of 75% compared to 60% with sunitinib alone.

The combination therapy also results in a higher objective response rate of 42% versus 27% for sunitinib, indicating that immune checkpoint inhibitors are becoming a promising first-line treatment option for metastatic RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontline immunotherapy treatment with nivolumab and ipilimumab in metastatic renal cell cancer: a new standard of care. Nizam, A., Aragon-Ching, JB.[2020]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05935748

NCT05935748 | Ph2 Study NKT2152 with Palbociclib & ... This is a Phase 2 open-label, multicenter, global study of NKT2152. This study is designed as two phases: a Lead-in phase and an Expansion phase.

2. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT05935748

UCSD CcRCC Trial → Ph2 Study NKT2152 with Palbociclib ... A Phase 2 Trial to Evaluate the Safety and Efficacy of NKT2152 in Combination with Palbociclib (Doublet) and with Palbociclib and Sasanlimab (Triplet)

3. onclive.com onclive.com/view/nkt2152-data-reinforce-the-importance-of-hif2-inhibition-in-advanced-clear-cell-rcc

NKT2152 Data Reinforce the Importance of HIF2α ... NKT2152 showed a 20% ORR in all-comers and 26.3% in dose-escalation for advanced RCC, with better outcomes in favorable-risk and mTOR-naive ...

4. urologytimes.com urologytimes.com/view/nkt2152-shows-strong-efficacy-in-advanced-clear-cell-renal-cell-carcinoma

NKT2152 shows strong efficacy in advanced clear cell ... “NKT2152 demonstrated robust anti-tumor activity in a heavily pretreated, high-risk advanced clear cell renal cell carcinoma population," said ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36456385/

A Multinational, Pooled Analysis From the Ibrance Real ... The 12-month progression-free rate was 88% for palbociclib plus an AI and 79% for palbociclib plus fulvestrant; the 12-month survival rate was 96% in both ...

6. adisinsight.springer.com adisinsight.springer.com/trials/700345690

A Phase 2 Trial to Evaluate the Safety and ... - AdisInsight This study will evaluate NKT2152 in combination with palbociclib and sasanlimab for the treatment of advanced clear cell renal cell ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-11193

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