Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - Other
Status
Ongoing, recruiting
Participants planned
240
Countries
6
Sites
19
Untreated Advanced or Metastatic Non-Small Cell Lung Cancer
To evaluate the safety and tolerability of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B) and Single-agent divarasib (Cohorts C and D)
Key facts
- Sponsor
- F. Hoffmann-La Roche AG
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 21 Jun 2023 → ongoing
- Decision date (initial)
- 2024-06-03
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- F. Hoffmann-La Roche AG
External identifiers
- EU CT number
- 2023-507171-22-00
- EudraCT number
- 2022-003048-28
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Safety, Efficacy
To evaluate the safety and tolerability of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B) and Single-agent divarasib (Cohorts C and D)
Secondary objectives 5
- To evaluate the activity of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B) and Single-agent divarasib (Cohorts C and D)
- To evaluate the tolerability of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B) and Single-agent divarasib (Cohorts C and D)
- To characterize the divarasib PK profile
- To identify a recommended dose of divarasib in combination regimens with pembrolizumab (Cohort A1) and pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B)
- To evaluate the central nervous system (CNS) activity of single-agent divarasib (Cohort D)
Conditions and MedDRA coding
Untreated Advanced or Metastatic Non-Small Cell Lung Cancer
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10061873 | Non-small cell lung cancer | 100000004864 |
| 21.1 | PT | 10059515 | Non-small cell lung cancer metastatic | 100000004864 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Overall Design Open-label, multicenter Phase Ib/II study designed to evaluate the safety, pharmacokinetics, and activity of divarasib in combination with other anti-cancer therapies in patients with untreated advanced or metastatic NSCLC that harbors a KRAS G12C mutation. This study is designed with the intention to include new, additional treatment arms during study
|
Randomised Controlled | None | Cohort A: Test Compounds for Cohort A: divarasib, pembrolizumab (parallel assignment) Cohort B: Test Compound for Cohort B: divarasib, pembrolizumab, pemetrexed, carboplatin, cisplatin (open-label) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
- No prior systemic treatment for advanced unresectable or metastatic NSCLC
- Adequate cardiovascular function as evidenced by the following: no significant cardiovascular disease within 3 months prior to initiation of study treatment and baseline corrected QT interval <=470 ms
- Pretreatment tumor tissue along with an associated pathology report is required for all participants enrolled on study. Representative tumor specimens must be in formalin‑fixed, paraffin-embedded (FFPE) blocks (preferred) or 15 unstained, freshly cut, serial slides. Although 15 slides are required, if only 10 slides are available, the participant may be eligible for the study following consultation with the Sponsor.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Exclusion criteria 7
- Known concomitant second oncogenic driver with available targeted treatment
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases (Cohort A, B and C)
- Prior treatment with a KRAS G12C inhibitor
- Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only)
- History of malignancy other than NSCLC within 5 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate more >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
- Uncontrolled tumor-related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia
- Significant cardiovascular disease within 3 months prior to initiation of study treatment , including any of the following: hypertensive crisis or encephalopathy; unstable angina; transient ischemic attack or stroke; congestive heart failure (NYHA class 2 or higher); serious cardiac arrythmia requiring treatment; history of thromboembolic events
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- 1. Occurrence of adverse events
- 2. Change from baseline at each visit in targeted safety parameters
Secondary endpoints 11
- 1. Objective response rate
- 2. Duration of response
- 3. Progression free survival
- 4. CNS response defined as the percentage of participants who experience a complete response or partial response in the brain, as determined by the investigator according to modified RECIST (Cohort D Only)
- 5. Change from baseline in symptomatic side effects, as assessed through use of the PRO-CTCAE
- 6. Proportion of participants reporting "frequent" or "almost constant" diarrhea during the first three cycles of treatment according to the PRO-CTCAE criteria
- 7. Proportion of participants reporting "severe" or "very severe" nausea or vomiting during the first three cycles of treatment according to the PRO-CTCAE
- 8. Frequency of participant's response of the degree they are troubled with treatment symptoms, as assessed through use of the single-item European Organisation for Research and Treatment of Cancer (EORTC) Item List 46 (IL46)
- 9. Plasma concentration of divarasib at specified timepoints
- 10. Recommended dose of divarasib in combination with pembrolizumab (Cohort A) or pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B) based on the totality of safety, activity, and PK data
- 11. Presence, frequency of occurrence, severity, and/or degree of interference with daily function of symptomatic side effects as assessed through use of the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO‑CTCAE)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 17
Cisplatin NeoCorp 1 mg/ml - Konzentrat zur Herstellung einer Infusionslösung
PRD759858 · Product
- Active substance
- Cisplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- L01XA01 — CISPLATIN
- Marketing authorisation
- 39021.01.00
- MA holder
- HEXAL AG
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
CISPLATINE ACCORD 1 mg/ml, solution à diluer pour perfusion
PRD415259 · Product
- Active substance
- Cisplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- L01XA01 — CISPLATIN
- Marketing authorisation
- 34009 576 157 7 2
- MA holder
- ACCORD HEALTHCARE FRANCE SAS
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
Cisplatin Teva® 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung
PRD662245 · Product
- Active substance
- Cisplatin
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- L01XA01 — CISPLATIN
- Marketing authorisation
- 71983.00.00
- MA holder
- TEVA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
CARBOPLATINE ACCORD 10 mg/ml, solution pour perfusion
PRD415296 · Product
- Active substance
- Carboplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- L01XA02 — CARBOPLATIN
- Marketing authorisation
- 34009 572 558 7 9
- MA holder
- ACCORD HEALTHCARE FRANCE SAS
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
Carboplatin-GRY® 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung
PRD664576 · Product
- Active substance
- Carboplatin
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- L01XA02 — CARBOPLATIN
- Marketing authorisation
- 44922.00.00
- MA holder
- TEVA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
CARBO-cell® 10 mg/ml Infusionslösung, Konzentrat zur Herstellung einer Infusionslösung
PRD1969079 · Product
- Active substance
- Carboplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- L01XA02 — CARBOPLATIN
- Marketing authorisation
- 46297.00.00
- MA holder
- STADAPHARM GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
Pemetrexed Fresenius Kabi 25 mg/ml concentrate for solution for infusion
PRD7936183 · Product
- Active substance
- Pemetrexed
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- L01BA04 — -
- Marketing authorisation
- EU/1/16/1115/004
- MA holder
- FRESENIUS KABI DEUTSCHLAND GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
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
- 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
- Yes
- Modification description
- Relabeled for CT use
ALIMTA 100 mg powder for concentrate for solution for infusion
PRD2426372 · Product
- Active substance
- Pemetrexed
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- L01BA04 — -
- Marketing authorisation
- EU/1/04/290/002
- MA holder
- ELI LILLY NEDERLAND B.V.
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
SUB09655MIG · Substance
- Active substance
- Pemetrexed
- Pharmaceutical form
- POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
SUB09655MIG · Substance
- Active substance
- Pemetrexed
- Pharmaceutical form
- POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
Pemetrexed Accord 25 mg/ml concentrate for solution for infusion
PRD8505444 · Product
- Active substance
- Pemetrexed
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- L01BA04 — -
- Marketing authorisation
- EU/1/15/1071/005
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
KEYTRUDA 25 mg/mL concentrate for solution for infusion
PRD4323105 · Product
- Active substance
- Pembrolizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- 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
- Yes
- Modification description
- Relabeled for CT use
KEYTRUDA 25 mg/mL concentrate for solution for infusion.
PRD12081132 · Product
- Active substance
- Pembrolizumab
- Substance synonyms
- Lambrolizumab, MK-3475, SCH-900475, BAT3306, Pabolizumab, FYB206, ABP 234
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- L01FF02 — -
- Marketing authorisation
- EU/1/15/1024/003
- MA holder
- MERCK SHARP & DOHME B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
PRD11081693 · Product
- Active substance
- Divarasib
- Other product name
- GDC-6036
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Authorisation status
- Not Authorised
- MA holder
- GENENTECH, INC.
- Paediatric formulation
- No
- Orphan designation
- No
PRD11081695 · Product
- Active substance
- Divarasib
- Other product name
- GDC-6036
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Authorisation status
- Not Authorised
- MA holder
- GENENTECH, INC.
- Paediatric formulation
- No
- Orphan designation
- No
PRD11081694 · Product
- Active substance
- Divarasib
- Other product name
- GDC-6036
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Authorisation status
- Not Authorised
- MA holder
- GENENTECH, INC.
- Paediatric formulation
- No
- Orphan designation
- No
Auxiliary 1
Budenofalk 3mg magensaftresistente Hartkapseln
PRD808682 · Product
- Active substance
- Budesonide
- Pharmaceutical form
- GASTRO-RESISTANT CAPSULE, HARD
- Route of administration
- INTRAVENOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- A07EA06 — BUDESONIDE
- Marketing authorisation
- 81258.00.00
- MA holder
- DR. FALK PHARMA G.M.B.H.
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for CT use
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
F. Hoffmann-La Roche AG
- Sponsor organisation
- F. Hoffmann-La Roche AG
- Address
- Grenzacherstrasse 124
- City
- Basel
- Postcode
- 4058
- Country
- Switzerland
Scientific contact point
- Organisation
- F. Hoffmann-La Roche AG
- Contact name
- Trial Information System - TISL
Public contact point
- Organisation
- F. Hoffmann-La Roche AG
- Contact name
- Trial Information System - TISL
Third parties 9
| Organisation | City, country | Duties |
|---|---|---|
| Labcorp Central Laboratory Services SARL ORG-100011524
|
Meyrin, Switzerland | Laboratory analysis |
| CellCarta ORG-100039881
|
Antwerp, Belgium | Laboratory analysis |
| Labcorp Early Development Laboratories Inc. ORG-100012865
|
Madison, United States | Laboratory analysis |
| Almac Clinical Technologies LLC ORG-100043036
|
Souderton, United States | Interactive response technologies (IRT) |
| Foundation Medicine Inc. ORG-100040457
|
Cambridge, United States | Laboratory analysis |
| Median Technologies ORG-100041462
|
Valbonne, France | Other |
| Pharmaceutical Product Development LLC ORG-100016999
|
Richmond, United States | Laboratory analysis |
| Axon Communications Inc. ORG-100048038
|
Toronto, Canada | Other |
| IQVIA Limited ORG-100008655
|
Reading, United Kingdom | Other |
Locations
6 EU/EEA countries · 19 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 29 | 4 |
| Italy | Ongoing, recruiting | 20 | 3 |
| Netherlands | Ongoing, recruiting | 30 | 2 |
| Poland | Ongoing, recruiting | 8 | 3 |
| Spain | Ongoing, recruiting | 25 | 6 |
| Sweden | Ongoing, recruiting | 4 | 1 |
| Rest of world
Israel, Brazil, United Kingdom, Australia, Switzerland, Argentina, China, Korea, Republic of, Taiwan, Canada, United States
|
— | 124 | — |
Investigational sites
Algemeen Ziekenhuis Delta
Department of respiratory diseases, Deltalaan 1, 8800, Roeselare
Cliniques Universitaires Saint-Luc
Medical oncology, Hippokrateslaan 10, Batiment 54, Sint-Lambrechts-Woluwe
Jessa Ziekenhuis
Oncology, Stadsomvaart 11, 3500, Hasselt
Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
Oncology, Place Louise Godin 15, 5000, Namur
Fondazione IRCCS Istituto Nazionale Dei Tumori
Medical Oncology and Hematology, Via Giacomo Venezian 1, 20133, Milan
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Thoracic Oncology, Regione Gonzole 10, 10043, Orbassano
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Clinical Trials Center, Largo Agostino Gemelli 8, 00168, Rome
Radboud universitair medisch centrum / RADBOUDUMC
pulmonary diseases, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
pulmonary oncology, Plesmanlaan 121, 1066 CX, Amsterdam
Warminsko-Mazurskie Centrum Chorob Pluc W Olsztynie
Oddział Onkologii z Pododdziałem Chemioterapii, Ul. Jagiellonska Nr 78, 10-357, Olsztyn
Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II
Oddział Onkologii z Pododdziałem Diagnostyki Nowotworów Klatki Piersiowej, Ul. Pradnicka 80, 31-202, Cracow
Uniwersyteckie Centrum Kliniczne
Ośrodek Badań Klinicznych Wczesnych Faz, Ul. Mariana Smoluchowskiego 17, 80-214, Gdansk
Hospital General Universitario Gregorio Maranon
Oncology, Calle Del Doctor Esquerdo 46, 28009, Madrid
University Hospital Virgen Del Rocio S.L.
Oncology, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Germans Trias I Pujol
Oncology, Carretera Canyet 1a Planta, 08916, Badalona
Hospital Universitari Vall D Hebron
Oncology, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Hospital Clinico Universitario De Valencia
Oncology, Avenida Blasco Ibanez 17, 46010, Valencia
Hospital Universitario 12 De Octubre
Oncology, Bloque D, Avenida De Cordoba Sn, 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 |
|---|---|---|---|---|---|
| Belgium | 2023-06-21 | 2023-06-22 | |||
| Italy | 2023-12-18 | 2024-01-31 | |||
| Netherlands | 2023-08-25 | 2023-09-14 | |||
| Poland | 2023-07-17 | 2024-01-31 | |||
| Spain | 2023-07-21 | 2023-08-04 | |||
| Sweden | 2023-09-18 | 2024-08-06 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 82 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-507171-22-00 Redacted | 7EEA-CH-TR |
| Protocol (for publication) | d4_patient-facing-documents_ctcae_be-fr | 1 |
| Protocol (for publication) | d4_patient-facing-documents_ctcae_be-nl | 1 |
| Protocol (for publication) | d4_patient-facing-documents_ctcae_en | 1 |
| Protocol (for publication) | d4_patient-facing-documents_ctcae_es | 1 |
| Protocol (for publication) | d4_patient-facing-documents_ctcae_it | 1 |
| Protocol (for publication) | d4_patient-facing-documents_ctcae_se | 1 |
| Protocol (for publication) | d4_patient-facing-documents_il46_be-fr | N/A |
| Protocol (for publication) | d4_patient-facing-documents_il46_be-nl | N/A |
| Protocol (for publication) | d4_patient-facing-documents_il46_en | N/A |
| Protocol (for publication) | d4_patient-facing-documents_il46_es | N/A |
| Protocol (for publication) | d4_patient-facing-documents_il46_it | N/A |
| Protocol (for publication) | d4_patient-facing-documents_il46_se | N/A |
| Protocol (for publication) | d4_patient-facing-documents_redaction-memo | N/A |
| Recruitment arrangements (for publication) | K Rcurit_arrenge_doc | 1.0 |
| Recruitment arrangements (for publication) | K1_ Recruiment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_ Recuritment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 3.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recrutiment arrangements and informed consent procedure | 1 |
| Subject information and informed consent form (for publication) | L!_SIS and ICF IAF | 3 |
| Subject information and informed consent form (for publication) | L1_Privacy consent form other subject | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS BO44426_ICF disease progression | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS BO44426_ICF optional biopsy | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS BO44426_ICF Pregnant partner | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biopsy | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF for the use and sharing of infant health information | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF IAF_EN | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF IAF_FR | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF IAF_NL | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main | 6 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_EN_REDACTED | 6.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_FR_REDACTED | 6.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_NL_REDACTED | 6.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF main_REDACTED | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PPA | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PPA_EN_REDACTED | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PPA_FR_REDACTED | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PPA_NL_REDACTED | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PPA_REDACTED | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pregnancy partner_REDACTED | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Prescreening_REDACTED | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF RBR | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF RBR Prescreening | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF RBR_REDACTED | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Apparent progression | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Appendix 1 Risk_redacted | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Appendix 2 GDPR | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Appendix 3_Optional biopsy_redacted | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Appendix 4_Treatment after progress | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Appendix 5_Optional lumbar puncture | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_IAF | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_IAF | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Lumbar Puncture_Clean | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_redacted | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_REDACTED | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_optional procedure_REDACTED | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_PPA | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_PPA_REDACTED | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_RBR_REDACTED | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ISF OPT. BIOPSY_REDACTED | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS BO44426 ICF infant authorization | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS BO44426_ ICF Main_redacted | 6.3 |
| Subject information and informed consent form (for publication) | L1_SIS BO44426_ICF RBR | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS_BO44426_ICF optionele lumbaal punctie_Final | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS_ICF_BO44426_Puncion lumbar opcional_2025_11_28 | 1 |
| Subject information and informed consent form (for publication) | L2_Informed consent form procedure | 3.0 |
| Subject information and informed consent form (for publication) | L2_Sponsor statement on use of ICF model | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC CARBOPLATINE ACCORD | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC CISPLATINE ACCORD | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC KEYTRUDA 25 mg mL concentrate for solution for infusion | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Pemetrexed Accord | NA |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ENG 2023-507171-22-00 | 7 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_be-de-2023-507171-22-00 | 7 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_be-fr-2023-507171-22-00 | 7 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_be-nl-2023-507171-22-00 | 7 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_es-2023-507171-22-00 | 7 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_it-2023-507171-22-00 | 7 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_nl-nl-2023-507171-22-00 | 7 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_pl-2023-507171-22-00 | 7 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_se-2023-507171-22-00 | 7 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-23 | Netherlands | Acceptable 2024-05-27
|
2024-05-27 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-10-18 | Netherlands | Acceptable 2025-02-10
|
2025-02-10 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-08-04 | Netherlands | Acceptable 2025-10-20
|
2025-10-20 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-12-15 | Netherlands | Acceptable with conditions 2026-04-14
|
2026-04-15 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-04-23 | Netherlands | Acceptable with conditions 2026-04-14
|
2026-04-23 |