Clinical trial NCT05485896: Neoadjuvant Therapy of Pembrolizumab Plus Lenvatinib in Advanced RCC
Official title: A Prospective Single-arm Clinical Study of Pembrolizumab Combined With Lenvatinib Neoadjuvant Therapy in Patients With Advanced Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Keywords: Pembrolizumab; Lenvatinib; Advanced Renal Cell Carcinoma
Lead sponsor: Tianjin Medical University Second Hospital
Sponsor class: OTHER
First posted: 2022-08-03
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

Brief summary: This is a phase II study to determine the efficacy and safety of Pembrolizumab when given in combination with Lenvatinib as treatment for patients with the advanced kidney cancer. Further evaluate whether the treatment plan is beneficial to the patient's surgery.

Detailed description: This is a phase II study to determine the efficacy and safety of Pembrolizumab when given in combination with Lenvatinib as treatment for patients with the advanced kidney cancer . Further evaluate whether the treatment is beneficial to operation. Patients will receive treatment with Pembrolizumab in combination with Lenvatinib every 3 weeks for 3 cycles in the preoperation. Additional 17 cycles of Pembrolizumab were needed for patients with high risk of recurrence (tumor stage 2 with nuclear grade IV or sarcomatoid differentiation, tumor stage 3 or higher, regional lymph-node metastasis, or stage M1 with no evidence of disease residual).

Eligibility criteria: Inclusion Criteria:

1. Willing and able to provide written informed consent;
2. Age ≥ 18 years and age ≤75years;
3. Patients with pathologically and radiographically confirmed clear cell renal cell carcinoma with clinical staging: cTanyN1Many, cTanyNanyM1, cT3-4NanyMany, and all visible lesions could be excised or ablation treated;
4. Enhanced imaging evaluation can be performed;
5. There are no suspected brain metastases;
6. The presence of measurable lesions was assessed according to RECISTv1.1 criteria;
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1;
8. Organ function level must meet the following requirements:

   Hematological indexes: neutrophil count \>= 1.5x10\^9/L, platelet count \>= 100x10\^9/L, hemoglobin \>= 9.0 g/dl (can be maintained by blood transfusion); Liver function: total bilirubin \<=1.5 ULN, alanine aminotransferase and aspartate aminotransferase \<=1.5 ULN;
9. Women were required to use an effective contraceptive method for three months after the end of the study, and men were required to consent to use an effective contraceptive method with their spouse during and for three months after the end of the study;
10. The subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up.

Exclusion Criteria:

1. Prior treatment with radiation, chemotherapy, long-term or high-dose hormone therapy, or immune checkpoint inhibitors;
2. Previous or concurrent other malignancy;
3. Previous PD-L1 or PD-L1 treatment, or allergy to PD-L1;
4. History of primary immunodeficiency;
5. Active, known or suspected autoimmune diseases;
6. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
7. Pregnant or lactating female patients;
8. Untreated acute or chronic active hepatitis B or hepatitis C infection. Under the condition of monitoring the virus copy number of patients receiving antiviral treatment, doctors can judge whether they are in line with the patients' individual conditions;
9. Have a clear history of active tuberculosis;
10. Participating in other clinical researchers;
11. Men with reproductive capacity or women who are likely to become pregnant do not take reliable contraceptive measures;
12. Uncontrolled concurrent diseases, including but not limited to:

HIV infected (HIV antibody positive); Severe infection in active stage or poorly controlled; Evidence of serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension \[i.e. hypertension greater than or equal to CTCAE grade 2 after drug treatment\]); Patients with active bleeding or new thrombotic disease.

Primary outcomes:
measure: Tumor responses
timeFrame: Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).
measure: Adverse events
timeFrame: Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).
Secondary outcomes:
measure: Tumor viability assessment
timeFrame: Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).
measure: Progression free survival
timeFrame: Every 12 weeks until 12 months after surgery
Other outcomes:
measure: Rate of responser with predictive biomarker positive
timeFrame: Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).
Locations:
city: Tianjin
country: China
facility: Changyi Quan
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Second Hospital
name: Changyi Quan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grunwald V, Hutson TE, Kopyltsov E, Mendez-Vidal MJ, Kozlov V, Alyasova A, Hong SH, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK; CLEAR Trial Investigators. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021 Apr 8;384(14):1289-1300. doi: 10.1056/NEJMoa2035716. Epub 2021 Feb 13.
citation: Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, Hajek J, Symeonides SN, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Gurney H, Chevreau C, Melichar B, Kopyltsov E, Alva A, Burke JM, Doshi G, Topart D, Oudard S, Hammers H, Kitamura H, Bedke J, Perini RF, Zhang P, Imai K, Willemann-Rogerio J, Quinn DI, Powles T; KEYNOTE-564 Investigators. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med. 2021 Aug 19;385(8):683-694. doi: 10.1056/NEJMoa2106391.