Clinical trial • Phase I/II|Phase II • Oncology

PEMBROLIZUMAB for Renal cell carcinoma

Phase I/II|Phase II trial of PEMBROLIZUMAB for Renal cell carcinoma. Randomised, adaptive. 194 participants.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Renal cell carcinoma
Trial Stage
Phase I/II|Phase II
Drug Modality
Monoclonal antibody|Small molecule

Key dates

Initial CTIS Submission Date
12-12-2023
First CTIS Authorization Date
22-01-2024

Trial design

Randomised, adaptive Phase I/II|Phase II trial in Netherlands, Spain, Poland and others.

Randomised
Yes
Adaptive
True, Safety lead-in phase to assess safety/tolerability and to establish a Recommended Phase 2 Dose (RP2D) if applicable; the design includes a safety lead-in (dose-finding) followed by an efficacy phase.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
194

Eligibility

Recruits 194 Vulnerable population not selected (isVulnerablePopulationSelected=false). Informed consent is required from participants; subject information and informed consent forms are listed in the documentation (multiple language versions present). No specific assent or additional vulnerable-population consent procedures are described in the record..

Pregnancy Exclusion
Female participants must not be pregnant and not be a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, and vibostolimab/pembrolizumab, for 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last and must abstain from breastfeeding during the study intervention period and for at least 120 days after study intervention
Vulnerable Population
Vulnerable population not selected (isVulnerablePopulationSelected=false). Informed consent is required from participants; subject information and informed consent forms are listed in the documentation (multiple language versions present). No specific assent or additional vulnerable-population consent procedures are described in the record.

Inclusion criteria

  • {"criterion_text":"- Has a histologically confirmed diagnosis of locally advanced/metastatic clear cell renal cell carcinoma (ccRCC)\n- Has received no prior systemic therapy for advanced RCC; prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed ≥12 months before randomization/allocation.\n- Is able to swallow oral medication\n- Has adequate organ function\n- Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation\n- Has resolution of toxic effects of the most recent prior therapy to ≤Grade 1\n- Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation\n- Male participants are abstinent from heterosexual intercourse or agree to use contraception during treatment with and for at least 7 days after the last dose of lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped, if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, vibostolimab/pembrolizumab or a combination of the aforementioned drugs, no contraception is needed\n- Female participants must not be pregnant and not be a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, and vibostolimab/pembrolizumab, for 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last and must abstain from breastfeeding during the study intervention period and for at least 120 days after study intervention"}

Exclusion criteria

  • {"criterion_text":"- Has urine protein ≥1 g/24 hours and has any of the following: (a) a pulse oximeter reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c) requires chronic supplemental oxygen (d) active hemoptysis within 3 weeks prior to the first dose of study intervention\n- Has received more than 4 previous systemic anticancer treatment regimens\n- Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention\n- Has known additional malignancy that is progressing or has required active treatment within the past 3 years\n- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis\n- Has an active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed\n- Has an active infection requiring systemic therapy\n- Has a known history of human immunodeficiency virus (HIV) infection\n- Has a known history of Hepatitis B\n- Has had an allogenic tissue/solid organ transplant\n- Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration\n- Has had major surgery within 3 weeks before first dose of study interventions\n- Has a history of lung disease\n- Has a history of inflammatory bowel disease\n- Has preexisting gastrointestinal (GI) or non-GI fistula\n- Has malabsorption due to prior GI surgery or disease\n- Has received prior radiotherapy within 2 weeks of start of study intervention\n- Has received a live or live attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- afety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)","definition_or_measurement_approach":"Count of participants experiencing one or more dose-limiting toxicities observed during the Safety Lead-in Phase."}
  • {"endpoint_text":"- Safety Lead-in Phase: Number of participants who experience one or more adverse events (AEs)","definition_or_measurement_approach":"Count of participants experiencing one or more adverse events during the Safety Lead-in Phase."}
  • {"endpoint_text":"- Safety Lead-in Phase: Number of participants who discontinue study treatment due to an AE","definition_or_measurement_approach":"Count of participants who discontinue study treatment as a result of an adverse event during the Safety Lead-in Phase."}
  • {"endpoint_text":"- Efficacy Phase: Number of participants who experience one or more DLTs","definition_or_measurement_approach":"Count of participants experiencing one or more dose-limiting toxicities during the Efficacy Phase."}
  • {"endpoint_text":"- Efficacy Phase: Number of participants who experience one or more AEs","definition_or_measurement_approach":"Count of participants experiencing one or more adverse events during the Efficacy Phase."}
  • {"endpoint_text":"- Efficacy Phase: Number of participants who discontinue study treatment due to an AE","definition_or_measurement_approach":"Count of participants who discontinue study treatment because of an adverse event during the Efficacy Phase."}
  • {"endpoint_text":"- Efficacy Phase: Objective response rate (ORR)","definition_or_measurement_approach":"Objective response rate assessed per RECIST 1.1."}

Secondary endpoints

  • {"endpoint_text":"- Efficacy Phase: Duration of response (DOR)","definition_or_measurement_approach":"Duration of response measured per RECIST 1.1."}
  • {"endpoint_text":"- Efficacy Phase: Progression-free survival (PFS)","definition_or_measurement_approach":"Progression-free survival assessed per RECIST 1.1."}
  • {"endpoint_text":"- Efficacy Phase: Overall survival (OS)","definition_or_measurement_approach":"Overall survival (time from randomization/allocation to death from any cause)."}
  • {"endpoint_text":"- Efficacy Phase: Clinical benefit rate (CBR)","definition_or_measurement_approach":"Clinical benefit rate assessed per RECIST 1.1."}

Recruitment

Planned Sample Size
194
Recruitment Window Months
65
Consent Approach
Informed consent is required from participants. Subject information and informed consent form (L1_ICF) documents are listed for multiple countries/languages (e.g. Spain, Poland, Hungary, France). No specific assent procedures or additional vulnerable-population consent procedures are described in the record.

Geography

Total Number Of Sites
12
Total Number Of Participants
62

Netherlands

Earliest CTIS Part Ii Submission Date
03-01-2024
Latest Decision Or Authorization Date
11-09-2024
Processing Time Days
252
Number Of Sites
3
Number Of Participants
4

Sites

Site Name
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Department Name
Medical Oncology
Contact Person Name
Koen van der Mijn
Contact Person Email
k.vd.mijn@nki.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Medical Oncology
Contact Person Name
Astrid van der Veldt
Contact Person Email
a.vanderVeldt@Erasmusmc.nl
Site Name
Universitair Medisch Centrum Utrecht
Department Name
Medical Oncology
Contact Person Name
Britt Suelmann
Contact Person Email
oncostudies@umcutrecht.nl

Spain

Earliest CTIS Part Ii Submission Date
03-01-2024
Latest Decision Or Authorization Date
01-04-2026
Processing Time Days
819
Number Of Sites
2
Number Of Participants
16

Sites

Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Medical Oncology Department
Contact Person Name
Pablo Gajate Borau
Contact Person Email
pgajateborau@gmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Medical Oncology Department
Contact Person Name
Cristina Suarez Rodriguez
Contact Person Email
csuarez@vhio.net

Poland

Earliest CTIS Part Ii Submission Date
03-01-2024
Latest Decision Or Authorization Date
03-04-2026
Processing Time Days
821
Number Of Sites
2
Number Of Participants
10

Sites

Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Centrum Wsparcia Badan Klinicznych UCK Osrodek Badan Klinicznych Wczesnych Faz
Contact Person Name
Rafał Dziadziuszko
Contact Person Email
obkwf@uck.gda.pl
Site Name
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Department Name
Ambulatorium chemioterapii
Contact Person Name
Bogdan Żurawski

Hungary

Earliest CTIS Part Ii Submission Date
03-01-2024
Latest Decision Or Authorization Date
31-03-2026
Processing Time Days
818
Number Of Sites
1
Number Of Participants
9

Sites

Site Name
Orszagos Onkologiai Intezet
Department Name
Gyógszerterápiás Központ, Urogenitális Tumorok és Klinikai Farmakológiai Osztály, Kemoterápia C”
Contact Person Name
Lajos Géczi
Contact Person Email
geczi.lajos@oncol.hu

France

Earliest CTIS Part Ii Submission Date
03-01-2024
Latest Decision Or Authorization Date
07-05-2026
Processing Time Days
855
Number Of Sites
4
Number Of Participants
23

Sites

Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Medical Oncology
Contact Person Name
Barthelemy Philippe
Site Name
Institut De Cancerologie De Lorraine
Department Name
Département d'oncologie médicale
Contact Person Name
Sophie Martin
Contact Person Email
so.martin@nancy.unicancer.fr
Site Name
Institut Gustave Roussy
Department Name
Département d’Oncologie Médicale
Contact Person Name
Laurence ALBIGES
Site Name
Institut Universitaire Du Cancer Toulouse-Oncopole
Department Name
Not applicable
Contact Person Name
Carlos Alberto Gomez Roca

Sponsor

Primary sponsor

Full Name
Merck Sharp & Dohme LLC
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
PPD Global Central Labs
Responsibilities
code:4
Name
Almac Clinical Technologies LLC
Responsibilities
code:3
Name
PRA International
Responsibilities
Central imaging
Name
Parexel International Corp.
Responsibilities
EUB services (call center and medical services)

Third parties

  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"code:3","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PRA International","duties_or_roles":"Central imaging","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"EUB services (call center and medical services)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
KEYTRUDA 25 mg/mL concentrate for solution for infusion
Active Substance
PEMBROLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
2
Investigational Product Name
MK-7684A
Active Substance
PEMBROLIZUMAB, VIBOSTOLIMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
1
Investigational Product Name
MK-1308A
Active Substance
PEMBROLIZUMAB, QUAVONLIMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
1
Investigational Product Name
Belzutifan
Active Substance
BELZUTIFAN
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
1
Investigational Product Name
MK-4280A
Active Substance
PEMBROLIZUMAB, FAVEZELIMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
1
Investigational Product Name
Lenvatinib
Active Substance
LENVATINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
1
Combination Treatment
Yes

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