Efficacy of PErioperative PEmbrolizumab treatment in patients with resectable metastases from kidney cancer. The PE-PE study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Consorzio Oncotech

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Mar 2025 → ongoing

Decision date (initial)

2024-09-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

MERCK SHARP & DOHME LLC

External identifiers

EU CT number

2024-512180-31-00

EudraCT number

2022-001077-30

ClinicalTrials.gov

NCT05578664

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of pembrolizumab in delaying tumor progression in patients with oligo-metastatic mRCC who are candidates for radical surgery and/or definite RT on tumor metastases.

Secondary objectives 4

1. To evaluate the efficacy of pembrolizumab in delaying distant tumor progression in patients with oligo-metastatic mRCC who are candidates for radical surgery and/or definite RT on tumor metastases.
2. To assess if peri-operative pembrolizumab compared to local treatment alone increases the mRCC patients’ survival.
3. To evaluate the safety of peri-operative pembrolizumab.
4. To evaluate the efficacy of perioperative pembrolizumab plus definitive RT in the local control of treated metastatic lesions

Conditions and MedDRA coding

Oligometastatic renal cell carcinoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of clear cell renal cell carcinoma will be enrolled in this study. 2. Have undergone a partial nephrectomy or radical complete nephrectomy with negative surgical margins. 3. Evidence of oligo-metastatic disease eligible for local treatment with radiotherapy or surgery, defined as: a) Appearance of new metastases within 5 years from previous eradication of primary tumors or previous metastasectomy. b) Presence of maximum 3 metastases in the same site or in different sites with the exception of bone metastases that cannot exceed the number of 2 if they are the sole disease site or one in case of multiple sites. c) Each metastasis should be less than 3 cm in the maximum diameter and less than 5 cm in the sum of the longest tumor diameters (this evaluation should apply also for lymph nodes). 4. Has received no prior systemic therapy for RCC. 5. Has ECOG performance status of 0 to 1 within 7 days of before the start of study intervention. 6. The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. 7. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a primary tumor or tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slide. Newly obtained biopsies are preferred to archived tissue. Female participants: 8. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatment(s)) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity after the last dose of study treatment. 9. Adequate organ function

Exclusion criteria 2

1. 1. Has had major surgery, other than nephrectomy, within 4 weeks prior to randomization. Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 2. Has residual thrombus post nephrectomy in the vena renalis or vena cava. 3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137). 4. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible 5. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, undergone CABG or PTCA, or cardiac arrhythmia. Note: Medically controlled arrhythmia stable on medication is permitted. 6. Has moderate to severe hepatic impairment (Child-Pugh B or C). 7. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. 8. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. 9. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. 10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 11. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-muscle invasive bladder cancer, prostate cancer pT2 or less, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. 12. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously surgically treated brain metastases may participate provided they are not radiological evidence of disease at the time of screening and without evidence of progression for at least 12 months by repeat imaging (note that the repeat imaging should be performed during study screening). 13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. 14. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. 15. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
2. 16.Has an active infection requiring systemic therapy. 17.Has a known history of Human Immunodeficiency Virus (HIV) infection. 18. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. 19. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 20. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 21. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. 22. Has had an allogenic tissue/solid organ transplant. 23. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess the relapsed free survival (RFS) defined as the length of time from the randomization and the appearance of radiological progression of kidney cancer in patients who received pembrolizumab compared to those who did not.

Secondary endpoints 4

1. • To assess the distant relapsed free survival (dRFS) in patients who received pembrolizumab compared to those who did not. The dRFS was defined as the length of time from the randomization to the appearance of distant metastases outside those treated with surgery or radiotherapy
2. • To assess the overall survival defined as the time from the randomization to the patient’s death or last contact in patients who received pembrolizumab compared to those who did not.
3. • To assess the overall incidence of adverse events in patients who received pembrolizumab compared to those who did not.
4. • To assess the overall incidence local progression in patients who received pembrolizumab plus RT compared to those who received RT alone.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Consorzio Oncotech

Sponsor organisation

Consorzio Oncotech

Address

Via Sergio Pansini 5

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

Consorzio Oncotech

Contact name

Roberto Iacovelli

Public contact point

Organisation

Consorzio Oncotech

Contact name

Roberto Iacovelli

Locations

1 EU/EEA country · 34 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications