Combining pembrolizumab with radiotherapy for advanced kidney cancer

A Phase II,Single-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab and Stereotactic Radiotherapy (SBRT) in Patients Advanced Metastatic Renal Clear Cell Carcinoma.

This study is testing if combining a drug called pembrolizumab with targeted radiation therapy can help people with advanced kidney cancer feel better and improve their treatment outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Nanfang Hospital, Southern Medical University (Academic / other)
• Drugs / interventions: pembrolizumab, chemotherapy, radiation, prednisone
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT05567588 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial investigates the effectiveness of combining pembrolizumab, an immune checkpoint inhibitor, with stereotactic body radiation therapy (SBRT) in patients with advanced clear-cell metastatic renal cell carcinoma (mRCC). The study aims to determine if this treatment strategy can enhance the activity of pembrolizumab, particularly in patients with PD-1 expressing immune cells. Participants will receive pembrolizumab followed by SBRT targeting the most significant metastatic lesions. The goal is to assess whether this combination warrants further investigation in larger randomized trials.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with advanced clear-cell metastatic renal cell carcinoma and a good performance status.

Not a fit: Patients with non-clear-cell renal cancer or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could improve survival rates and outcomes for patients with advanced renal cancer.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and radiotherapy, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Age\> 18 years at the time of signing informed consent;
* ECOG score of 0 or 1;
* Histologically confirmed, advanced ccRCC of stage IV (AJCC 8);
* Life expectancy of more than 12 weeks;
* Evidence of measurable metastatic kidney cancer according to RECIST 1.1 criteria. Patients should have an adequate number of non-irradiated metastatic sites in order to adequately assess the activity of the pembrolizumab therapy;
* If central nervous system (CNS) metastases are treated before inclusion and the patient's neurological system is present Return of symptoms to baseline levels (except for signs or symptoms associated with CNS therapy)At least 14 days, such patients may be included. In addition, patients must stop taking glucocorticoids or prednisone in a stable dose and ≤ 10 mg per day;
* Main organ function meets the following criteria within 7 days before treatment:

  1. blood examination criteria (in the state without blood transfusion within 14 days): ① Hemoglobin(HB) ≥ 70 g/L; ② Absolute Neutrophil Count(ANC) ≥ 1.0×109/L; ③ Platelet (PLT) ≥ 60×109/L.
  2. Biochemical examination shall meet the following criteria: ① total bilirubin within 1.5×the upper limit of normal(ULN); ② serum transaminase≤2.5×the Upper Limit of Normal(ULN), If associated with liver metastasis, serum transaminase≤5.0×the Upper Limit of Normal(ULN);③ serum creatine ≤ 1.5 x Upper Limit of Normal(ULN),creatinine clearance rate ≥ 60ml/min;
* Women of childbearing age should agree to use contraception (e. g. intrauterine device, contraceptive or condom) within 6 months after study completion, the pregnancy test results (serum or urine) within 7 days before enrolment must be negative;
* Men should agree that contraception must be used during and within 6 months of the end of the study period;
* With consent and have signed the informed consent, willing and able to comply with the planned visits, research treatment, laboratory tests, and other experimental procedures.

Exclusion Criteria:

* Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2;
* Any active or recently diagnosed clear or suspected autoimmune disorder disease, or symptoms requiring glucocorticoids (\> 10 mg/day) or immunosuppressive drugs for systemic therapy;
* Active brain metastases and/or cancerous meningitis;
* Has had a prior monoclonal antibody within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier;
* Has more than one previous chemotherapy,targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent;
* Diagnosed with immunodeficiency within 2 weeks prior to study or being treated with systemic glucocorticoids or any other form of immunosuppressive therapy;
* Have a positive history of human immunodeficiency virus (HIV) test or have acquired immunodeficiency syndrome (AIDS);
* Has known active Hepatitis B or Hepatitis C;
* Has a known additional malignancy that is progressing or requires active treatment;
* Have interstitial lung disease, active pulmonary infectious pneumonia, or grade 3 or higher pneumonia;
* Patients with mental or physical illnesses (such as infectious diseases) requiring compulsory isolation treatment;
* Has received a live vaccine within 30 days prior to the first dose of trial treatment; · · According to the investigator, there may be increased risk associated with participation in the study, or other severe, acute or chronic medical or psychiatric disorders that may interfere with the interpretation of the findings.

Where this trial is running

Guangzhou, Guangdong and 1 other locations

• Guozhu,Xie — Guangzhou, Guangdong, China (Recruiting)
• Nanfang Hospital, Southern Medical University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Guozhu Xie

Conditions Clear-cell Metastatic Renal Cell Carcinoma; pembrolizumab; stereotactic radiotherapy