Atezolizumab, Pertuzumab and Trastuzumab with chemotherapy as neoadjuvant treatment of HER2 positive early high-risk and locally advanced breast cancer (APTneo)

2024-518026-32-00 Protocol FM-17-B01 Therapeutic confirmatory (Phase III) Authorised, recruitment pending

Status Authorised, recruitment pending · 6 EU/EEA countries · 63 sites · Protocol FM-17-B01

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Authorised, recruitment pending
Participants planned 661
Countries 6
Sites 63

Invasive Breast Cancer

Compare 5-year Event-Free Survival (EFS) between Arm B (B1+B2) and Arm A. Depending on the superiority of the primary efficacy endpoint (EFS), a formal comparison of Arm B1 vs Arm A, Arm B2 vs Arm A will be conducted. Comparison of Arm B1 vs Arm B2 will be conducted in an exploratory manner

Key facts

Sponsor
Fondazione Michelangelo
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Decision date (initial)
2024-11-25
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
F. Hoffmann-La Roche Ltd - Basel

External identifiers

EU CT number
2024-518026-32-00
EudraCT number
2017-000981-31
ClinicalTrials.gov
NCT03595592

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Compare 5-year Event-Free Survival (EFS) between Arm B (B1+B2) and Arm A. Depending on the superiority of the primary efficacy endpoint (EFS), a formal comparison of Arm B1 vs Arm A, Arm B2 vs Arm A will be conducted. Comparison of Arm B1 vs Arm B2 will be conducted in an exploratory manner

Secondary objectives 8

  1. Compare the rate of pathological complete response (pCR), defined as absence of invasive cells in breast and nodes (ypT0/is and ypN0) at surgery, in Arm B vs Arm A.
  2. Compare clinical overall response (cOR) at the end of neo-adjuvant therapy
  3. Compare Disease-Free Survival (DFS) from the time of surgery in Arm B vs Arm A
  4. Compare Distant EFS (DEFS) from the time of randomization
  5. Compare overall survival from the time of randomization
  6. Evaluate tolerability of the treatment regimens in the different study arms
  7. Composition and specificity of the immune infiltrate of the tumor and of draining lymph nodes
  8. Conduct molecular and clinical analyses to assess the presence of predictive markers of benefit or resistance to the study regimens

Conditions and MedDRA coding

Invasive Breast Cancer

VersionLevelCodeTermSystem organ class
20.0 LLT 10006283 Breast neoplasm malignant female 10029104

Study design 3 periods

#TitleAllocationBlindingRoles blindedArms
1 Neoadjuvant Treatment
All patients will receive a combination of trastuzumab, pertuzumab, carboplatin and paclitaxel; only patients enrolled in Arm B1 will receive Doxorubicin or Epirubicin and Cyclophosphamide; patients enrolled in Arm B1 and B2 will also receive Atezolizumab.
 Randomised Controlled None Arm A: Protocol V1.0+2.0:

1)Trastuzumab 8 mg/kg loading dose i.v., then 6 mg/kg i.v. q.3 wks;
2)Pertuzumab 840 mg loading dose i.v., then 420 mg i.v. q. 3 wks;
3)Carboplatin AUC 2 i.v. on day 1 and day 8 q. 3 wks;
4)Taxol (paclitaxel) 90 mg/m2 i.v. on day 1 and day 8 q. 3 wks
for 6 cycles.
____________________________________________________
Protocol V3.0 (not applicable to Romanian sites)
1) PH FDC (Fixed-dose combination of SC pertuzumab and trastuzumab)
The initial dose is 1,200 mg pertuzumab, 600 mg trastuzumab, and
30,000 units hyaluronidase administered subcutaneously
followed every 3 wks by a dose of 600 mg pertuzumab, 600 mg
trastuzumab, and 20,000 units hyaluronidase administered
subcutaneously;
2)Carboplatin AUC 2 i.v. on day 1 and day 8 q. 3 wks;
3)Taxol (paclitaxel) 90 mg/m2 i.v. on day 1 and day 8 q. 3 wks
for 6 cycles.
Arm B1: Protocol V1.0+2.0
1)Anthracycline:
-Adriamycin 60 mg/m2 i.v. q. 3 wks or Epirubicin 90 mg/m2 i.v. q. 3 wks;
2) Cyclophosphamide 600 mg/m2 i.v. q. 3 wks;
3)Atezolizumab 1200 mg i.v. infusion q. 3 wks;

for 3 cycles followed by:

4)Trastuzumab 8 mg/kg loading dose i.v., then 6 mg/kg i.v. q.3 wks;
5)Pertuzumab 840 mg loading dose i.v., then 420 mg i.v. q. 3 wks;
6)Carboplatin AUC 2 i.v. on day 1 and day 8 q. 3 wks;
7)Taxol (paclitaxel) 90 mg/m2 i.v. on day 1 and day 8 q. 3 wks
8) Atezolizumab 1200 mg i.v. infusion q. 3 wks.
for 3 cycles
____________________________________________________
Protocol V3.0 (not applicable to Romanian sites):
1)Anthracycline:
-Adriamycin 60 mg/m2 i.v. q. 3 wks or Epirubicin 90 mg/m2 i.v. q. 3 wks
2)Cyclophosphamide 600 mg/m2 i.v. q. 3 wks;
3)Atezolizumab 1200 mg i.v. infusion q 3 wks for 3 cycles;

followed by

4)PH FDC (Fixed-dose combination of SC pertuzumab and trastuzumab):
The initial dose is 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase administered subcutaneously over approximately 8 minutes, followed every 3 wks by a dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase;
5)Carboplatin AUC 2 i.v. on day 1 and day 8 q. 3 wks;
6)Taxol (paclitaxel) 90 mg/m2 i.v. on day 1 and day 8 q. 3 wks;
7)Atezolizumab 1200 mg i.v. infusion q 3 wks;

for 3 cycles.
Arm B2: Protocol V1.0+2.0:

1)Trastuzumab 8 mg/kg loading dose i.v., then 6 mg/kg i.v. q.3 wks;
2)Pertuzumab 840 mg loading dose i.v., then 420 mg i.v. q. 3 wks;
3)Carboplatin AUC 2 i.v. on day 1 and day 8 q. 3 wks;
4)Taxol (paclitaxel) 90 mg/m2 i.v. on day 1 and day 8 q. 3 wks;
5)Atezolizumab 1200 mg i.v. infusion q. 3 wks.

for 6 cycles
____________________________________________________
Protocol V3.0 (not applicable to Romanian sites):

1)PH FDC (Fixed-dose combination of SC pertuzumab and trastuzumab): The initial dose is 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase administered subcutaneously over approximately 8 minutes, followed every 3 wks by a dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase;
2)Carboplatin AUC 2 i.v. on day 1 and day 8 q. 3 wks;
3)Taxol (paclitaxel) 90 mg/m2 i.v. on day 1 and day 8 q. 3 wks;
4)Atezolizumab 1200 mg i.v. infusion q. 3 wks;

for 6 cycles

NOTE: in all the three arms, patients randomized under Protocol V1 or V2 who have not completed the neoadjuvant treatment at the time of Protocol V3 approval and have signed the amended ICF, may switch to the fixed-dose combination of SC pertuzumab and trastuzumab.
2 Adjuvant Treatment
After completion of the neoadjuvant and surgical treatment, patients will receive Trastuzumab + Pertuzumab or Trastuzumab Emtansine (all Arms) and Atezolizumab (only Arm B1 and B2).
 Randomised Controlled None Arm A: Patients will receive:
Protocol V1.0+2.0

-Trastuzumab 6 mg/kg i.v. q.3 wks and Pertuzumab 420 mg i.v. q. 3 wks
for 12 additional cycles.

Protocol V3.0 (not applicable to Romanian sites)
Patients who achieved a pathological complete remission will receive:

-PH FDC (Fixed-dose combination of SC pertuzumab and trastuzumab) at the dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase administered subcutaneously to be repeated q. 3 wks for 12 additional cycles.

Patients with residual invasive disease at surgery will receive:
-Trastuzumab emtansine 3.6 mg/kg infusion q. 3 wks for 12 cycles
Arm B1: Patients will receive:
Protocol V1.0+2.0:

Atezolizumab 1200 mg i.v. infusion q 3 wks for 12 additional cycles and Trastuzumab 6 mg/kg i.v. q.3 wks and Pertuzumab 420 mg i.v. q. 3 wks for 15 additional cycles.

Protocol V3.0 (not applicable to Romanian sites)
Patients who achieved a pathological complete remission will receive:

Atezolizumab 1200 mg i.v. infusion q. 3 wks for 14 additional cycles
and PH FDC (Fixed-dose combination of SC pertuzumab and trastuzumab) at the dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase administered subcutaneously to be repeated q. 3 wks for 14 additional cycles.

Patients with residual invasive disease at surgery will receive:
Atezolizumab 1200 mg i.v. infusion q. 3 wks for 14 additional cycles and Trastuzumab emtansine 3.6 mg/kg infusion q. 3 wks for 14 cycles.
Arm B2: Patients will receive:

Protocol V1.0+2.0:
Atezolizumab 1200 mg i.v. infusion q. 3 wks and Trastuzumab 6 mg/kg i.v. q.3 wks and Pertuzumab 420 mg i.v. q. 3 wks for 12 additional cycles.

Protocol V3.0 (not applicable to Romanian sites)
Patients who achieved a pathological complete remission will receive:

Atezolizumab 1200 mg i.v. infusion q 3 wks and PH FDC (Fixed-dose combination of SC pertuzumab and trastuzumab) at the dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase administered subcutaneously to be repeated q. 3 wks for 12 additional cycles.

Patients with residual invasive disease at surgery will receive:
Atezolizumab 1200 mg i.v. infusion q. 3 wks for 12 additional cycles and Trastuzumab emtansine 3.6 mg/kg infusion q. 3 wks, for 12 cycles.
3 Follow-up
After adjuvant treatment completion, all patients must be followed for a minimum of 5 years after the date of randomization of the last partecipant any change in cancer related history and adverse events must be reported.
 Not Applicable None

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

  1. Female patients aged 18 years or older with early high-risk ((T1cN1; T2N1; T3N0) or locally advanced and inflammatory breast cancers (stage III A-C according to AJCC) suitable for neoadjuvant treatment
  2. Histologically confirmed unilateral invasive breast cancer
  3. HER2 positive disease according to ASCO/CAP current guidelines
  4. Known estrogen (ER) and progesterone receptor (PgR)
  5. Availability of a representative paraffin-embedded (FFPE) tumor block taken at diagnostic biopsy for central confirmation of HER2 eligibility, for assessment of ER, PgR, Ki67 and PD-L1 expression and for biomarker evaluation is mandatory
  6. Consent to the collection of blood samples mandatorily before starting neoadjuvant treatment, after the first cycle of therapy, at the end of neoadjuvant treatment (before surgery), 6 months after surgery and at the end of all treatments.
  7. ECOG performance status 0 or 1
  8. For women who are not postmenopausal (≥ 12 months of non-therapyinduced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study drugs. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Examples of contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization (not acceptable in Germany), hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices
  9. Written informed consent to participate in the trial (approved by the Institutional Review Board [IRB]/ Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
  10. Willing and able to comply with the protocol

Exclusion criteria 29

  1. Evidence of bilateral breast cancer or metastatic disease (M1)
  2. Patients with HER2-negative defined as 0-1+ by immunohistochemistry or 2+ by immunohistochemistry without HER2 amplification by either In Situ Hybridization (ISH) or other amplification tests done locally are considered not eligible for the study
  3. Pregnant or lactating women. Documentation of a negative pregnancy test must be available for premenopausal women with intact reproductive organs and for women less than one year after the last menstrual cycle
  4. Women with childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception as mentioned at point 8. of inclusion criteria
  5. Previous treatment with chemotherapy, hormonal therapy or an investigational drug for any type of malignancy; only for patients enrolled in Germany: presence of bleeding tumors.
  6. Previous investigational treatment for any condition other than malignancy within 4 weeks of randomization date; only for patients enrolled in Germany: or within 5 half-lives, whichever is longer.
  7. Administration of a live, attenuated vaccine within 4 weeks before Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  8. Previous or concomitant malignancy of any other type that could affect compliance with the protocol or interpretation of results. Patients with curatively treated basal cell carcinoma of the skin or in situ cervix cancer are eligible
  9. Pre-existing motor or sensory neuropathy of grade > 1 for any reason
  10. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins or hyaluronidase; only for patients enrolled in Germany: history of severe allergic reactions to any protocol anticancer agent or any of the excipients
  11. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
  12. Patients with prior allogeneic stem cell or solid organ transplantation
  13. History of autoimmune disease including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Bell’s palsy, GuillainBarré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix A for preexisting autoimmune diseases and immune deficiencies)
  14. History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography scan
  15. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
  16. History of HIV infection, active hepatitis B (chronic or acute), or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive hepatitis B core antibody [anti-HBc] test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction assay (PCR) is negative for HCV RNA Only for patients enrolled in Germany: all patients have to undergo hepatitis and HIV testing during screening in order to adequately determine the infection status and ensure that patients with an active infection will be excluded from the trial.
  17. Active tuberculosis
  18. Severe infections within 4 weeks prior to Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. Signs or symptoms of significant infection within 2 weeks prior to Day 1
  19. Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
  20. Other serious illness or medical condition, including but not limited to history of documented congestive cardiac failure; New York Heart Association (NYHA) Class II or greater CHF; angina pectoris requiring anti-anginal medication or unstable angina within 6 months prior to Day 1; evidence of transmural infarction on ECG; myocardial infarction stroke or transient ischemic attack (TIA) within 6 months prior to Day 1; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias; severe dyspnea at rest requiring supplementary oxygen therapy; uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently); Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected calcium > ULN)
  21. Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drugs
  22. Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes mellitus
  23. Any of the following abnormal baseline hematological values: a. White blood count (WBC) < 2.5 x 109 /L b. Absolute Neutrophil Count (ANC) < 1.5 × 109 /L c. Lymphocyte count < 0.5 x 109 /L d. Platelet count < 100 × 109 /L e. Hemoglobin (Hb) < 10 g/dL
  24. Any of the following abnormal baseline laboratory tests a. Serum total bilirubin > 1.5 × ULN (upper limit of normal) (except for patients with clearly documented Gilbert’s syndrome) b. Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.25 × ULN c. Alkaline phosphatase > 2.5× ULN d. Serum creatinine > 1.5 × ULN e. INR and aPTT > 1.5 × ULN within 2 weeks prior to enrollment. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose
  25. Baseline left ventricular ejection fraction (LVEF) < 55% by echocardiography or multi-gated scintigraphic scan (MUGA)
  26. Major surgical procedure within 28 days prior to Day 1 or anticipation of need for a major surgical procedure during the course of the study
  27. Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Day 1 or at any time during the study; only for patients enrolled in Germany: the concomitant administration of yellow-fever vaccine is not allowed.
  28. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti−CTLA-4, anti−PD-1, and anti−PD-L1 therapeutic antibodies
  29. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Event Free Survival (EFS)

Secondary endpoints 6

  1. Pathological Complete Response (pCR)
  2. Relationship between pCR and EFS
  3. Clinical Overall Response (cOR) at the end of neo-adjuvant treatment
  4. Disease-Free Survival (DFS)
  5. Distant Event Free Survival
  6. Overall Survival

Investigational products

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

Test 5

Perjeta 420 mg concentrate for solution for infusion

PRD801541 · Product

Active substance
Pertuzumab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Max daily dose
840 mg milligram(s)
Max total dose
7980 mg milligram(s)
Max treatment duration
54 Week(s)
Authorisation status
Authorised
ATC code
L01XC13 — -
Marketing authorisation
EU/1/13/813/001
MA holder
ROCHE REGISTRATION GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
secondary packaging and labelling

Kadcyla 160 mg powder for concentrate for solution for infusion.

PRD974895 · Product

Active substance
Trastuzumab Emtansine
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Max daily dose
3 mg/kg milligram(s)/kilogram
Max total dose
42 mg/Kg milligram(s)/kilogram
Max treatment duration
42 Week(s)
Authorisation status
Authorised
ATC code
L01FD03 — -
Marketing authorisation
EU/1/13/885/002
MA holder
ROCHE REGISTRATION GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
secondary packaging and labelling

Phesgo 600 mg/600 mg solution for injection

PRD8601831 · Product

Active substance
Trastuzumab
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS USE
Max daily dose
600 mg milligram(s)
Max total dose
10200 mg milligram(s)
Max treatment duration
51 Week(s)
Authorisation status
Authorised
ATC code
L01XY02 — -
Marketing authorisation
EU/1/20/1497/002
MA holder
ROCHE REGISTRATION GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
secondary packaging and labelling

Tecentriq 1 200 mg concentrate for solution for infusion

PRD5434939 · Product

Active substance
Atezolizumab
Substance synonyms
RO5541267
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Max daily dose
1200 mg milligram(s)
Max total dose
24000 mg milligram(s)
Max treatment duration
60 Week(s)
Authorisation status
Authorised
ATC code
L01FF05 — -
Marketing authorisation
EU/1/17/1220/001
MA holder
ROCHE REGISTRATION GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
secondary packaging and labelling

Phesgo 1200 mg/600 mg solution for injection

PRD8600161 · Product

Active substance
Trastuzumab
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS USE
Max daily dose
1200 mg milligram(s)
Max total dose
2400 mg milligram(s)
Max treatment duration
6 Week(s)
Authorisation status
Authorised
ATC code
L01XY02 — -
Marketing authorisation
EU/1/20/1497/001
MA holder
ROCHE REGISTRATION GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
secondary packaging and labelling

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Michelangelo

Sponsor organisation
Fondazione Michelangelo
Address
Via Agostino Bertani 14
City
Milan
Postcode
20154
Country
Italy

Scientific contact point

Organisation
Fondazione Michelangelo
Contact name
Board of Directors’ designee

Public contact point

Organisation
Fondazione Michelangelo
Contact name
Board of Directors’ designee

Third parties 9

OrganisationCity, countryDuties
Michelangelo Tech S.r.l.
ORG-100050803
 Milan, Italy Code 10, Code 11, Code 12, Other, Code 9
Optimapharm Research RO S.R.L.
ORG-100034348
 Bucharest, Romania On site monitoring, Code 12
P.R.I.S.M.A.-CRO Clinical Research Organisation GmbH
ORG-100046769
 Langenfeld (Rheinland), Germany On site monitoring, Code 12
Fundacion Grupo Espanol De Investigacion En Cancer De Mama
ORG-100010747
 San Sebastian De Los Reyes, Spain On site monitoring, Code 12, Code 2
Mediolanum Cardio Research S.r.l.
ORG-100010094
 Milan, Italy On site monitoring
Istituto Europeo Di Oncologia S.r.l.
ORG-100009530
 Milan, Italy Other
Ad Hoc Clinical
ORG-100040439
 Ieper, Belgium On site monitoring, Code 12
Opis S.r.l.
ORG-100011127
 Desio, Italy Other, Data management, E-data capture, Code 8
ICTA Project Management En Abrege ICTA P.M.
ORG-100008364
 Fontaine Les Dijon, France On site monitoring, Code 12, Other

Locations

6 EU/EEA countries · 63 investigational sites

By country

CountryMS statusPlanned subjectsSites
Austria Authorised, recruitment pending 6 2
Belgium Authorised, recruitment pending 29 3
Germany Authorised, recruitment pending 65 12
Italy Authorised, recruitment pending 313 17
Romania Authorised, recruitment pending 11 2
Spain Authorised, recruitment pending 222 27
Rest of world
Taiwan
 — 15 —

Investigational sites

Austria

2 sites · Authorised, recruitment pending
Medical University Of Vienna
Frauenheilkunde, Klin. Abteilung für Allg. Gynäkologie und Gynäkologische Onkologie, Waehringer Guertel 18-20, Alsergrund, Vienna
Noe LGA Gesundheit Region Mitte GmbH
Klinische Abteilung für Innere Medizin 1, Dunant-Platz 1, 3100, St. Poelten

Belgium

3 sites · Authorised, recruitment pending
Ziekenhuis Aan De Stroom
Clinical Trial Oncology, Oosterveldlaan 24, 2610, Antwerp
Antwerp University Hospital
Clinical Trial Oncology, Drie Eikenstraat 655, 2650, Edegem
Clinique Saint-Pierre
Medical Oncology, Avenue Reine Fabiola 9, 1340, Ottignies-Louvain-La-Neuve

Germany

12 sites · Authorised, recruitment pending
MVZ Onko Medical GmbH
Gynäkologisch-Onkologische Praxis, Pelikanplatz 23, List, Hanover
Universitaetsklinikum Schleswig-Holstein AöR
Klinik für Frauenheilkunde und Geburtshilfe, Ratzeburger Allee 160, 23538, Luebeck
SRH Wald-Klinikum Gera GmbH
Brustzentrum Ostthüringen, Strasse Des Friedens 122, Debschwitz, Gera
Vincentius-Diakonissen-Kliniken gAG
Gynäkologie und Geburtshilfe, Steinhaeuserstrasse 18, Suedweststadt, Karlsruhe
Universitaetsklinikum Heidelberg AöR
Gynäkologische Onkologie, Im Neuenheimer Feld 460, Neuenheim, Heidelberg
St. Elisabeth Gruppe - Katholische Kliniken Rhein-Ruhr Marien Hospital Witten
Brustzentrum Witten, Marienplatz 2, 58452, Witten
Technische Universitaet Dresden
Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Fetscherstrasse 74, Johannstadt-Nord, Dresden
Agaplesion Frankfurter Diakonie Kliniken gGmbH
Klinik für Gynäkologie und Gynäkologische Onkologie, Wilhelm-Epstein-Strasse 4, Bockenheim, Frankfurt Am Main
Universitaetsklinikum Halle (Saale) AöR
Universitätsklinik und Poliklinik für Gynäkologie, Ernst-Grube-Strasse 40, Kroellwitz, Halle Saale
Klinikum Magdeburg gGmbH
Klinik für Hämatologie, Onkologie und Palliativmedizin, Birkenallee 34, Alt Olvenstedt, Magdeburg
Marienhospital Bottrop gGmbH
Gynäkologische Onkologie, Josef-Albers-Strasse 70, Sued-West-Innenstadt, Bottrop
St Johannes Hospital gGmbH
Klinik für Gynäkologie und Geburtshilfe, Johannesstrasse 9-17, 44137, Dortmund

Italy

17 sites · Authorised, recruitment pending
Azienda USL IRCCS Di Reggio Emilia
Medical Oncology, Viale Risorgimento 80, 42123, Reggio Emilia
Fondazione IRCCS Istituto Nazionale Dei Tumori
S. C. Medical Oncology 1, Via Giacomo Venezian 1, 20133, Milan
Azienda Sanitaria Locale Br
Medical Oncology, Senza Numero Civico, Strada Statale 7 Mesagne 1, Brindisi
Azienda Ospedaliero Universitaria Pisana
Medical Oncology 1, Via Roma 67, 56126, Pisa
Ospedale San Raffaele S.r.l.
Medical Oncology (1Q-A), Via Olgettina 60, 20132, Milan
I.F.O. Istituti Fisioterapici Ospitalieri
Medical Oncology, Via Elio Chianesi N 53, 00144, Rome
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
Medical Oncology, Piazza Oms 1, 24127, Bergamo
Azienda Ospedaliero Universitaria Di Modena
Medical Oncology, Largo Del Pozzo 71, 41124, Modena
Istituto Europeo Di Oncologia S.r.l.
Medical Oncology, Via Giuseppe Ripamonti 435, 20141, Milan
Azienda Sanitaria Universitaria Friuli Centrale
Medical Oncology, Piazzale Santa Maria Della Misericordia 15, 33100, Udine
IRCCS Ospedale Policlinico San Martino
Struttura Semplice Sviluppo di Terapie Innovative, Largo Rosanna Benzi 10, 16132, Genoa
Azienda Unita Sanitaria Locale Della Romagna
Medical Oncology, Viale Vincenzo Randi 5, 48121, Ravenna
IRCCS Ospedale Sacro Cuore Don Calabria
Medical Oncology, Via Don Angelo Sempreboni 5, 37024, Negrar
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Medical Oncology, Via Piero Maroncelli 40, 47014, Meldola
Azienda Unita Sanitaria Locale Della Romagna
Medical Oncology, Viale Luigi Settembrini 2, 47923, Rimini
Istituti Clinici Scientifici Maugeri S.p.A. Societa' Benefit In Forma Abbreviata Istituti Clinici Scientifici Maugeri S.p.A. Sb O Anche Ics Maugeri S.p.A. Sb O Maugeri S.p.A. Sb
Medical Oncology, Via Salvatore Maugeri 10, 27100, Pavia
ASST Fatebenefratelli Sacco
Medical Oncology, Via Giovanni Battista Grassi 74, 20157, Milan

Romania

2 sites · Authorised, recruitment pending
Institutul Oncologic Prof. Dr. Alexandru Trestioreanu Bucuresti
Radiotherapy Clinical Department II, Soseaua Fundeni 252, 022328, Bucharest
Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca
Radiotherapy I, Strada Republicii 34-36, 400015, Cluj-Napoca

Spain

27 sites · Authorised, recruitment pending
Fundacion Onkologikoa Fundazioa
Oncology, Pasealeku Doct. Begiristain 121, 20014, Donostia
Hospital Universitario De Badajoz
Oncology, Avenida Elvas S/n, 06006, Badajoz
Hospital Universitario Donostia
Oncology, Pasealeku Doct. Begiristain 109, 20014, Donostia
Hospital Universitario Fundacion Jimenez Diaz
Oncology, Avenida De Los Reyes Catolicos 2, 28040, Madrid
Hospital Universitario Virgen De Las Nieves
Oncology, Avenida De Las Fuerzas Armadas 2, 18014, Granada
Hospital Clinico San Carlos
Oncology, Calle Del Profesor Martín Lagos S/n, 28040, Madrid
Hospital San Pedro De Alcantara
Oncology, Avenida De Pablo Naranjo Porras S/n, 10002, Caceres
Hospital Universitario Miguel Servet
Oncology, Paseo De Isabel La Catolica 1-3, 50009, Zaragoza
Hospital General Universitario Dr. Balmis
Oncology, Avinguda Del Pintor Baeza 12, 03010, Alicante
Hospital Clinico Universitario Lozano Blesa
Oncology, Avenida De San Juan Bosco 15, 50009, Zaragoza
Hospital Virgen De Los Lirios
Oncology, Calle Caramanxel S/n, 03804, Alcoy
Complexo Hospitalario Universitario De Santiago
Oncology, Calle Choupana Da S/n, 15706, Santiago De Compostela
Hospital Clinico Universitario De Valencia
Oncology, Avenida Blasco Ibanez 17, 46010, Valencia
Hospital Universitario Basurto
Oncology, Montevideo Etorbidea 16-18, 48013, Bilbao
Clinica Universidad De Navarra
Oncology, Pio XII Etorbidea 36, 31008, Pamplona
Hospital General Universitario Morales Meseguer
Oncology, Avenida Del Marques De Los Velez S/n, 30008, Murcia
Hospital Del Mar
Oncology, Passeig Maritim De La Barceloneta 25-29, 08003, Barcelona
Hospital Clinic De Barcelona
Oncology, Calle Villarroel 170, 08036, Barcelona
MD Anderson Cancer Center
Oncology, Calle De Arturo Soria Nº 270, 28033, Madrid
Hospital General Universitario Gregorio Maranon
Oncology, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Universitario De Fuenlabrada
Oncology, Camino Del Molino 2, 28942, Fuenlabrada
Hospital Universitario Juan Ramon Jimenez
Oncology, Ronda Exterior Norte S/n, 21005, Huelva
Hospital De La Santa Creu I Sant Pau
Oncology, Calle De San Antonio Maria Claret 167, 08025, Barcelona
Fundacion Centro Oncologico Regional De Galicia Jose Antonio Quiroga Y Pineyro
Oncology, Rua Doctor Camilo Veiras 1, 15009, A Coruna
Hospital Universitario De Toledo
Oncology, Avenue Del Rio Guadiana Sn, 45007, Toledo
Hospital Universitario De Salamanca
Oncology, Paseo De San Vicente 58-182, 37007, Salamanca
Hospital Universitario Regional De Malaga
Oncology, Avenida De Carlos De Haya S/N, 29010, Malaga

Results and documents

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

Documents 44 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-518026-32-00 redacted 2
Recruitment arrangements (for publication) K1_NtF_Recruitment Arrangement 2
Recruitment arrangements (for publication) K1_NtF_Recruitment Arrangement 2
Recruitment arrangements (for publication) K1_Recruitment Arrangement 1
Recruitment arrangements (for publication) K1_Recruitment Arrangement 1
Recruitment arrangements (for publication) K1_Recruitment Arrangement 2.0
Recruitment arrangements (for publication) K1_Recruitment Arrangement_NTF NA
Subject information and informed consent form (for publication) L1_ Addendum 4 to ICF V2 and V3_31Jan2025_redacted 4
Subject information and informed consent form (for publication) L1_Addendum 2 of 21-Mar-2022_to ICF V2_0 and V3_0 1
Subject information and informed consent form (for publication) L1_Addendum 3 of 26-May-2023 to ICF V2_0 and V3_0 1
Subject information and informed consent form (for publication) L1_addendum 4 to ICF V 2 and V 3_31Jan2025 4
Subject information and informed consent form (for publication) L1_AT_Addendum 2_ v1_2 to ICF v2_0 and ICF v3_0 1.2
Subject information and informed consent form (for publication) L1_AT_Addendum 3 to ICF v2_0 and ICF v3_0 1
Subject information and informed consent form (for publication) L1_AT_ICF add 4 to ICF v.2.0 and 3.0 4
Subject information and informed consent form (for publication) L1_AT_ICF Biomaterial v1_2_for publication 1.2
Subject information and informed consent form (for publication) L1_AT_SIS and ICF Main for Patients V3_0_for publication 3.0
Subject information and informed consent form (for publication) L1_Belgium_FR_SIS and ICF_Addendum_2_forpub 1.0
Subject information and informed consent form (for publication) L1_Belgium_FR_SIS and ICF_Addendum_3_forpub 1.0
Subject information and informed consent form (for publication) L1_Belgium_FR_SIS and ICF_Addendum_4_forpub 1
Subject information and informed consent form (for publication) L1_Belgium_FR_SIS and ICF_main_forpub 3.0
Subject information and informed consent form (for publication) L1_Belgium_NL_SIS and ICF_Addendum_2_forpub 1.0
Subject information and informed consent form (for publication) L1_Belgium_NL_SIS and ICF_Addendum_3_forpub 1.0
Subject information and informed consent form (for publication) L1_Belgium_NL_SIS and ICF_Addendum_4_forpub 1
Subject information and informed consent form (for publication) L1_Belgium_NL_SIS and ICF_main_forpub 3.0
Subject information and informed consent form (for publication) L1_SIS and ICF Main for Patients V3_0_20210415_for publication 3.0
Subject information and informed consent form (for publication) L1_SIS and ICF Main_Addendum no-2 2
Subject information and informed consent form (for publication) L1_SIS and ICF Main_Addendum no-3 3
Subject information and informed consent form (for publication) L1_SIS and ICF Main_redacted 3.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Addendum 2 to ICF V2_0 and ICF V3_0 NA
Subject information and informed consent form (for publication) L1_SIS and ICF_Addendum 3 to ICF V2_0 and ICF V3_0 NA
Subject information and informed consent form (for publication) L1_SIS and ICF_Addendum 4 to ICF V2_0 and ICF V3_0 NA
Subject information and informed consent form (for publication) L1_SIS and ICF_Main_V3_0_Redacted 3.0
Subject information and informed consent form (for publication) L1_SIS and ICF_optional samples 1.1
Subject information and informed consent form (for publication) L1_SISandICFpatients_Addendum 2 to Main ICF_redacted 2
Subject information and informed consent form (for publication) L1_SISandICFpatients_Addendum 3 to Main ICF 3
Subject information and informed consent form (for publication) L1_SISandICFpatients_Main_V 4_ITA_redacted 4
Summary of Product Characteristics (SmPC) (for publication) E2_SmPc_Kadcyla 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPc_Perjeta 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPc_Phesgo 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPc_Phesgo 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPc_Tecentric 1
Synopsis of the protocol (for publication) D1_Protocol synopsis _ENG_2024-518026-32-00 4
Synopsis of the protocol (for publication) D1_Protocol synopsis _IT_2024-518026-32-00 1
Synopsis of the protocol (for publication) D1_Protocol synopsis V 4.1_DE_2024-518026-32-00 4.1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-16 Italy Acceptable
2024-11-20
 2024-11-21
2 SUBSTANTIAL MODIFICATION SM-1 2025-03-04 Italy Acceptable
2025-06-09
 2025-06-10
3 NON SUBSTANTIAL MODIFICATION NSM-1 2025-07-02 Italy Acceptable
2025-06-09
 2025-07-02
4 SUBSTANTIAL MODIFICATION SM-2 2025-07-16 Acceptable 2025-08-12
5 SUBSTANTIAL MODIFICATION SM-3 2025-07-21 Acceptable 2025-07-28
6 SUBSTANTIAL MODIFICATION SM-4 2025-10-27 Italy Acceptable
2026-02-05
 2026-02-06
7 SUBSTANTIAL MODIFICATION SM-5 2026-02-24 Italy Acceptable
2026-04-13
 2026-04-14

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