Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
739
Countries
5
Sites
27
Metastatic Non-Small Cell Lung Cancer
1. To compare MK-7684A in combination with chemotherapy to pembrolizumab in combination with chemotherapy with respect to Overall Survival (OS) in participants with PD-L1 TPS ≥1%
Key facts
- Sponsor
- Merck Sharp & Dohme LLC
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 22 Mar 2022 → 9 Jan 2026
- Decision date (initial)
- 2023-10-09
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Merck Sharp & Dohme LLC
External identifiers
- EU CT number
- 2023-506074-12-00
- EudraCT number
- 2021-004564-94
- WHO UTN
- U1111-1293-2114
- ClinicalTrials.gov
- NCT05226598
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Pharmacogenomic, Pharmacokinetic, Pharmacogenetic, Safety, Therapy, Efficacy
1. To compare MK-7684A in combination with chemotherapy to pembrolizumab in combination with chemotherapy with respect to Overall Survival (OS) in participants with PD-L1 TPS ≥1%
Secondary objectives 7
- To compare MK-7684A in combination with chemotherapy to pembrolizumab in combination with chemotherapy with respect to OS in all participants
- To compare MK-7684A in combination with chemotherapy to pembrolizumab in combination with chemotherapy with respect to progression-free survival (PFS) in participants with PD-L1 TPS≥1% and in all participants per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR)
- To evaluate MK-7684A in combination with chemotherapy to pembrolizumab in combination with chemotherapy with respect to Objective Response Rate (ORR) in participants with PD-L1 TPS≥1% and in all participants per RECIST 1.1 as assessed by BICR
- To evaluate the mean change from baseline in global health status/quality of life (QoL), physical functioning, role functioning, dyspnea, cough, and chest pain for MK-7684A in combination with chemotherapy compared to pembrolizumab in combination with chemotherapy in participants with PD-L1 TPS≥1% and in all participants
- To evaluate the time to deterioration in global health status/QoL, physical functioning, role functioning, dyspnea, cough, and chest pain for MK-7684A in combination with chemotherapy compared to pembrolizumab in combination with chemotherapy in participants with PD-L1 TPS≥1% and in all participants
- To evaluate the safety and tolerability of MK-7684A in combination with chemotherapy compared to pembrolizumab in combination with chemotherapy
- To evaluate DOR per RECIST 1.1 as assessed by BICR for MK-7684A plus chemotherapy compared to pembrolizumab plus chemotherapy in participants with PD-L1 TPS≥1% and in all participants
Conditions and MedDRA coding
Metastatic Non-Small Cell Lung Cancer
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10059515 | Non-small cell lung cancer metastatic | 100000004864 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- A histologically or cytologically confirmed diagnosis of Stage IV squamous or non-squamous NSCLC.
- Has not received prior systemic treatment for metastatic NSCLC.
- Has measurable disease based on RECIST 1.1, as determined by the local site assessment.
- Has a life expectancy of at least 3 months.
- Males: Use contraception unless confirmed to be azoospermic; Females: Women of childbearing potential use highly effective contraceptive method.
Exclusion criteria 14
- Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Severe hypersensitivity to MK-7684, MK-7684A, pembrolizumab, chemotherapy components, and/or any of its excipients.
- 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 before the first dose of study medication.
- Active autoimmune disease that has required systemic treatment in past 2 years, except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid).
- History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV), hepatitis B or/and hepatitis C virus.
- Received prior systemic anticancer therapy for metastatic disease.
- Received a live or live attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
- History of allogeneic tissue/solid organ transplant.
- Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g/day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
- Is unable or unwilling to take folic acid or vitamin B12 supplementation.
- Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Overall Survival (OS) in Participants with Programmed Cell Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1%
Secondary endpoints 18
- Overall Survival (OS)
- Progression-Free Survival (PFS)
- Objective Response Rate (ORR)
- Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
- Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
- Change from Baseline for Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30
- Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30
- Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13)
- Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ- LC13
- Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30
- TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ- C30
- TTD in Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30
- TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30
- TTD in Cough Score (Item 31) on the EORTC QLQ-LC13
- TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13
- Number of Participants Who Experienced One or More Adverse Events (AEs)
- Number of Participants Who Discontinued Study Intervention Due to an AE
- Duration of Response (DOR)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD9386962 · Product
- Active substance
- Pembrolizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 20800 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- MERCK & CO. INC.
- Paediatric formulation
- No
- Orphan designation
- No
Comparator 1
KEYTRUDA 25 mg/mL concentrate for solution for infusion
PRD4323105 · Product
- Active substance
- Pembrolizumab
- Substance synonyms
- Lambrolizumab, MK-3475, SCH-900475, ABP 234
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 200 mg milligram(s)
- Max total dose
- 10400 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01FF02 — -
- Marketing authorisation
- EU/1/15/1024/002
- MA holder
- MERCK SHARP & DOHME B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 8
SCP247399 · ATC
- Active substance
- Paclitaxel
- Substance synonyms
- ONCOGEL, ABI-007, MBT 0206
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 200 mg/m2 milligram(s)/square meter
- Max total dose
- 800 mg/m2 milligram(s)/square meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CD01 — PACLITAXEL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Abraxane 5 mg/ml powder for dispersion for infusion.
PRD9254301 · Product
- Active substance
- Paclitaxel Albumin-Bound
- Substance synonyms
- PACLITAXEL ALBUMINE-BOUND
- Pharmaceutical form
- DISPERSION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 100 mg/m2 milligram(s)/square meter
- Max total dose
- 1200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CD01 — PACLITAXEL
- Marketing authorisation
- EU/1/07/428/001
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Pazenir 5 mg/ml powder for dispersion for infusion.
PRD7328588 · Product
- Active substance
- Paclitaxel Albumin-Bound
- Substance synonyms
- PACLITAXEL ALBUMINE-BOUND
- Pharmaceutical form
- DISPERSION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 100 mg/m2 milligram(s)/square meter
- Max total dose
- 1200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CD01 — PACLITAXEL
- Marketing authorisation
- EU/1/18/1317/001
- MA holder
- RATIOPHARM GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09583MIG · Substance
- Active substance
- Paclitaxel
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 200 mg/m2 milligram(s)/square meter
- Max total dose
- 800 mg/m2 milligram(s)/square meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP26873719 · ATC
- Active substance
- Cisplatin
- Substance synonyms
- Cis-diamminedichloroplatinum, (SP-4-2)-cis -diamminedichloroplatinum, CDDP
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 75 mg/m2 milligram(s)/square meter
- Max total dose
- 300 mg/m2 milligram(s)/square meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XA01 — CISPLATIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP60141047 · ATC
- Active substance
- Pemetrexed
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 500 mg/m2 milligram(s)/square meter
- Max total dose
- 15500 mg/m2 milligram(s)/square meter
- Max treatment duration
- 93 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BA04 — PEMETREXED
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ALIMTA 500 mg powder for concentrate for solution for infusion
PRD2433080 · Product
- Active substance
- Pemetrexed
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 500 mg/m2 milligram(s)/square meter
- Max total dose
- 15500 mg/m2 milligram(s)/square meter
- Max treatment duration
- 93 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BA04 — -
- Marketing authorisation
- EU/1/04/290/001
- MA holder
- ELI LILLY NEDERLAND B.V.
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP28192792 · ATC
- Active substance
- Carboplatin
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 900 mg milligram(s)
- Max total dose
- 3600 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XA02 — CARBOPLATIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Merck Sharp & Dohme LLC
- Sponsor organisation
- Merck Sharp & Dohme LLC
- Address
- 126 East Lincoln Avenue
- City
- Rahway
- Postcode
- 07065-4607
- Country
- United States
Scientific contact point
- Organisation
- Merck Sharp & Dohme LLC
- Contact name
- Pierre Leconte
Public contact point
- Organisation
- Merck Sharp & Dohme LLC
- Contact name
- Pierre Leconte
Third parties 5
| Organisation | City, country | Duties |
|---|---|---|
| Bioclinica Inc. ORG-100033079
|
Princeton, United States | Other |
| Eresearchtechnology Inc. ORG-100013039
|
Philadelphia, United States | E-data capture |
| Fortrea Inc. ORG-100012602
|
Durham, United States | Other |
| Parexel International Corp. ORG-100007310
|
Auburndale, United States | Other |
| EndPoint ORL-000000834
|
San Francisco,, United States | Interactive response technologies (IRT) |
Locations
5 EU/EEA countries · 27 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ended | 18 | 4 |
| France | Ended | 42 | 5 |
| Germany | Ended | 27 | 5 |
| Poland | Ended | 39 | 7 |
| Spain | Ended | 64 | 6 |
| Rest of world
Mexico, United States, China, Korea, Republic of, Turkey, United Kingdom, Israel, Colombia, Chile, Thailand, Taiwan, Brazil, Argentina, Japan
|
— | 549 | — |
Investigational sites
Medical University Of Graz
Department of Internal Medicine, Division of Pulmonology, Auenbruggerplatz 15, 8036 Graz, Neue Stiftingtalstrasse 6, 8010, Graz
Ordensklinikum Linz GmbH
Department of Pneumology, Fadingerstrasse 1, 4020, Linz
Medizinische Universitaet Innsbruck
Department of Internal Medicine V, Hematology and Oncology, Anichstrasse 35, 6020, Innsbruck
Krankenhaus Nord Klinik Floridsdorf
Department for Respiratory and Critical Care Medicine, Bruenner Strasse 68, Floridsdorf, Vienna
Centre Leon Berard
Cancérologie Medicale - Poumons, 28 Rue Laennec, 69008, Lyon
Institut De Cancerologie De L Ouest
Service d'oncologie Médicale, 15 Rue Andre Boquel, 49100, Angers
Centre Hospitalier D Avignon
Service d'oncologie Médicale et d'hématologie clinique, 305 Rue Raoul Follereau, 84000, Avignon
Centre Hospitalier Universitaire De Lille
Department of Pulmonary and Thoracic Oncology, Boulevard Du Professeur Jules Leclercq, 59000, Lille
HIA Sainte Anne
n/a, 2 Boulevard Sainte Anne, Bp 600, Toulon Cedex 9
Justus-Liebig-Universitaet Giessen
Medizinische Klinik IV, Gaffkystrasse 5, 35392, Giessen
GEFOS Gesellschaft fuer onkologische Studien Dortmund mbH
GEFOS Gesellschaft fuer onkologische Studien Dortmund mbH, Am Knappschaftskrankenhaus 1, 44309, Dortmund
SRH Wald-Klinikum Gera GmbH
Zentrum für klinische Studien, Strasse Des Friedens 122, Debschwitz, Gera
Universitaetsklinikum Schleswig-Holstein
Med. Klinik III, Pneumologie-Infektiologie, Ratzeburger Allee 160, 23538, Lübeck
Charite Universitaetsmedizin Berlin KöR
Campus Virchow-Klinikum, Med. Klinik mit Schwerpunkt Infektiologie und Pneumologie, Augustenburger Platz 1, Wedding, Berlin
Med Polonia Sp. z o.o.
n/a, Obornicka 262, 60-693, Poznan
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Klinika Nowotworów Płuca i Klatki Piersiowej, Ul. Wilhelma Konrada Roentgena 5, 02-781, Warsaw
Centrum Pulmonologii I Torakochirurgii W Bystrej
Oddział Pulmonologiczno – Onkologiczny z Chemioterapią, Ul. Juliana Falata 2, Bystra, Wilkowice
Przychodnia Lekarska Komed Roman Karaszewski
n/a, ul. Wojska Polskiego 6, 62-500, Konin
Wojewodzki Szpital Im. Sw.Ojca Pio W Przemyslu
Oddział Onkologiczny z Pododdziałem Dziennej Chemioterapii, Ul. Monte Cassino 18, 37-700, Peremyshl
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Ambulatorium Chemioterapii, Ul. Izabeli Romanowskiej 2, 85-796, Bydgoszcz
Szpital Specjalistyczny W Prabutach Sp. z o.o.
Oddział Pulmonologii, Ul. Kuracyjna 30, 82-550, Prabuty
Complexo Hospitalario Universitario A Coruna
Medical Oncology, Lugar Jubias De Arriba 84, 15006, A Coruna
Complejo Hospitalario Universitario Insular Materno Infantil
Medical Oncology, Autovia Del Sur S/n, 35017, Las Palmas De Gran Canaria
Hospital Clinico Universitario Lozano Blesa
Medical Oncology, Avenida De San Juan Bosco 15, 50009, Zaragoza
Hospital Universitario Virgen De La Macarena
Medical Oncology, Avenida Del Doctor Fedriani 3, 41009, Sevilla
Hospital Universitari Vall D Hebron
Medical Oncology, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona
Hospital Clinico San Carlos
Medical Oncology, Calle Del Profesor Martin Lagos Sn, 28040, Madrid
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Austria | 2022-05-10 | 2025-12-19 | 2022-05-10 | 2023-04-26 | |
| France | 2022-05-13 | 2025-03-14 | 2022-05-16 | 2023-04-26 | |
| Germany | 2022-04-05 | 2025-07-25 | 2022-04-19 | 2023-04-26 | |
| Poland | 2022-05-11 | 2025-12-23 | 2022-07-08 | 2023-04-26 | |
| Spain | 2022-03-22 | 2025-05-29 | 2022-03-24 | 2023-04-26 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Urgent safety measures 1 · Art. 54 CTR
Urgent safety measure US-64404
- Event date
- 2024-12-16
- Submission date
- 2024-12-20
- In response to
- OTHER
- Member states affected
- Austria, France, Germany, Spain, Poland
- Event description
- KEYVIBE-007: A Randomized, Double-Blind, Phase 3 Study of MK-7684A Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy as First Line Treatment for Participants With Metastatic Non-Small Cell Lung Cancer (NCT 05226598, EU CT 2023-506074-12).
In a pre-planned analysis for KeyVibe-003 and KeyVibe-007 studies, both trials met the pre-specified futility criteria for the primary endpoint of overall survival. In these studies, the safety profile of the fixed-dose combination was consistent with that observed for vibostolimab (MK-7684) and pembrolizumab in previously reported studies, with no new safety signals identified. Based on the lack of efficacy in KeyVibe-003, KeyVibe-007, the previously announced Phase 3 studies, KeyVibe-010 in adjuvant melanoma and KeyVibe-008 in extensive-stage small cell lung cancer, and following the recommendations from the external Data Monitoring Committee (eDMC) to unblind the KeyVibe-003 and KeyVibe-007, crossover all patients receiving MK-7684A to pembrolizumab, and perform no additional analyses for the OS endpoint and secondary endpoints, MSD has decided to discontinue MK-7684/MK-7684A in all studies.
This decision is not based on any concerns about the safety of MK-7684/MK-7684A. - Measures taken
- As of 16DEC2024, 10 patients are currently active under MK-7684A in following EEA countries:
Number of patients active on MK7684A in EEA:
France: 2
Poland: 5
Spain: 3
Austria: 0
Germany: 0
The Sponsor issued a Communication to Investigator Letter on December 16, 2024, which is attached, requiring the following actions by investigator and site personnel:
1. All study participants receiving treatment with vibostolimab/pembrolizumab (MK-7684A) with or without chemotherapy should stop treatment with MK-7684A and be offered pembrolizumab with or without chemotherapy. Pembrolizumab may be sourced locally from commercial stock if needed until available through central sourcing and as of the event date (i.e. immediate implementation required).
2. The participants should be informed within 4 weeks of receiving Communication to Investigator Letter and communication with the participants should be documented in their medical records.
3. The study will remain open so that remaining participants on treatment will have continued access to pembrolizumab.
4. Data collection will be limited: response data will no longer be collected though documentation of AEs should remain uninterrupted. The study will close once all participants are no longer on study treatment. Second course pembrolizumab for patients currently not on second course treatment will continue to be offered for eligible patients.
5. The final visit in the study will be the Safety Follow-up Visit. There will be no follow-up for survival status. Participants currently in imaging follow-up or in survival follow-up are considered to have completed the study and therefore should obtain imaging and further oncological care as per local standard of care. However, standard safety reporting should continue, as applicable.
6. A planned substantial modification by early next year will be submitted to the Protocol and informed consent to reflect the clinical trial changes. - Justification
- added the substantial amendment plan to the impacted document as a measure taken by the Sponsor.
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 60 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2023-506074-12_SM03_for pub | 05R |
| Protocol (for publication) | D4_Copyright statement_EN_SM03_for pub | 04DEC2024 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure__FRA_FR_for pub | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_DEU_EN_for pub | 08DEC2023 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_FRA_FR_SM03_for pub | 28FEB2025 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_POL_PL_for pub | 22DEC2021R |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and ICF Procedure_FRA_FR_for pub | 19APR2022 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_ESP_ES_for pub | 17NOV2021R |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_FRA_FR_for pub | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Brochure_DEU_DE_for pub | 21MAR2022 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Master Tissue Brochure_FRA_FR_for pub | 11NOV2021 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_AUT_DE_for pub | 11NOv2021 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_FRA_FR_for pub | 11NOV2021 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Poster_FRA_FR_for pub | 11NOV2021 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_AUT_DE_for pub | 0.01R |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_DEU_DE_for pub | v01 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_ESP_ES_for pub | 01 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_FRA_FR_for pub | V01R |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_POL_PL_for pub | 01 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum disease progression_AUT_DE_for pub | AM01v1.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum disease progression_DEU_DE_for pub | AM01v1.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum disease progression_FRA_FR_for pub | AM02v2.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum disease progression_POL_PL_for pub | 1.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum side effects_AUT_DE_SM03_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum side effects_DEU_EN_SM03_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum trial closing_DEU_EN_SM03_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum trial Closing_FRA_FR_SM03_for pub | 0.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum_AUT_DE_SM03_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum_ESP_ES_SM03_for pub | 0.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum_FRA_FR_for pub | AM02v2.01 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum_FRA_FR_SM03_for pub | AM02v2.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum_FRA_FR_TC_not pub | AM02v2.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main addendum_Trial Closing_POL_PL_SM03_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_AUT_DE_for pub | AM02v2.01R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_DEU_DE_for pub | AM02v2.01R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_ESP_ES_SM03_for pub | AM02v2.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_FRA_FR_SM03_for pub | AM02v2.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_POL_PL_for pub | 2.01R |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_add crossborder_DEU_DE_for pub | v0.00R |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_addendum_ESP_ES_for pub | AM01v1.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_pregnancy follow-up_FRA_FR_for pub | AM01v1.00R |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_pregnant partner_ESP_ES_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_pregnant partner_FRA_FR_for pub | AM01v1.00R |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_withdrawal_ESP_ES_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_Patient contacts per site_0701_AUT_DE_for pub | 31JAN2024R |
| Subject information and informed consent form (for publication) | L1_Patient contacts per site_0703_AUT_DE_for pub | 09FEB2023 |
| Subject information and informed consent form (for publication) | L1_Patient contacts per site_0704_AUT_DE_for pub | 18JAN2024R |
| Subject information and informed consent form (for publication) | L1_Patient contacts per site_0704_O_AUT_DE_for pub | 25OCT2023R |
| Subject information and informed consent form (for publication) | L1_Patient contacts per site_0705_AUT_DE_for pub | 08FEB2022R |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Pembrolizumab_SM03-RFI001_for pub | 06FEB2025 |
| Synopsis of the protocol (for publication) | D1_PPLS_2023-506074-12_ESP_ES_SM03_for pub | 3.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2023-506074-12_FRA_FR_SM03_for pub | 3.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2023-506074-12_POL_PL_SM03_for pub | 3.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2023-506074-12_SM03_for pub | 3.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_AUT_DE_2023-506074-12_for pub | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_2023-506074-12_AUT_DE_SM03_for pub | 05 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_DEU_DE_2023-506074-12_for pub | 01 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_ESP_ES_2021-004564-94_for pub | 01R |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_FRA_FR_2023-506074-12_for pub | 2.0R |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_POL_PL_2023-506074-12_for pub | 01R |
Application history
9 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-09-01 | France | Acceptable 2023-09-27
|
2023-09-29 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-04-29 | France | Acceptable 2024-07-24
|
2024-07-24 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-09-20 | France | Acceptable 2025-01-15
|
2025-01-15 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-03-05 | France | Acceptable 2025-05-05
|
2025-05-06 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-08-20 | France | Acceptable 2025-05-05
|
2025-08-20 |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-08-27 | France | Acceptable 2025-05-05
|
2025-08-27 |
| 7 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-09-18 | Acceptable 2025-05-05
|
2025-09-18 | |
| 8 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2025-10-01 | France | Acceptable 2025-05-05
|
2025-10-01 |
| 9 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-11-07 | Acceptable 2025-12-19
|
2025-12-22 |