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JOURNAL ONKOLOGIE – STUDIE

A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer

Rekrutierend

NCT-Nummer:
NCT06103864

Studienbeginn:
November 2023

Letztes Update:
19.04.2024

Wirkstoff:
Dato-DXd, Durvalumab, Paclitaxel, Nab-Paclitaxel, Gemcitabine, Carboplatin, Pembrolizumab

Indikation (Clinical Trials):
Breast Neoplasms, Triple Negative Breast Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
AstraZeneca

Collaborator:
Daiichi Sankyo

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com» Kontaktdaten anzeigen

Studienlocations
(3 von 279)

Research Site
40479 Düsseldorf
(Nordrhein-Westfalen)
GermanyZurückgezogen» Google-Maps
Research Site
45136 Essen
(Nordrhein-Westfalen)
GermanyZurückgezogen» Google-Maps
Research Site
49124 Georgsmarienhütte
(Niedersachsen)
GermanyZurückgezogen» Google-Maps
Research Site
30625 Hannover
(Niedersachsen)
GermanyZurückgezogen» Google-Maps
Research Site
69120 Heidelberg
(Baden-Württemberg)
GermanyZurückgezogen» Google-Maps
Research Site
74078 Heilbronn
(Baden-Württemberg)
GermanyZurückgezogen» Google-Maps
Research Site
36526 Daphne
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
72762 Springdale
United StatesNoch nicht rekrutierend» Google-Maps
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91204 Glendale
United StatesNoch nicht rekrutierend» Google-Maps
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95817 Sacramento
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
95403 Santa Rosa
United StatesNoch nicht rekrutierend» Google-Maps
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80012 Aurora
United StatesNoch nicht rekrutierend» Google-Maps
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06510 New Haven
United StatesNoch nicht rekrutierend» Google-Maps
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32256 Jacksonville
United StatesNoch nicht rekrutierend» Google-Maps
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33176 Miami
United StatesNoch nicht rekrutierend» Google-Maps
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32909 Palm Bay
United StatesNoch nicht rekrutierend» Google-Maps
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30318 Atlanta
United StatesNoch nicht rekrutierend» Google-Maps
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96819 Honolulu
United StatesNoch nicht rekrutierend» Google-Maps
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60637 Chicago
United StatesNoch nicht rekrutierend» Google-Maps
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60540 Naperville
United StatesNoch nicht rekrutierend» Google-Maps
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47150 New Albany
United StatesNoch nicht rekrutierend» Google-Maps
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50309 Des Moines
United StatesNoch nicht rekrutierend» Google-Maps
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40503 Lexington
United StatesNoch nicht rekrutierend» Google-Maps
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40202 Louisville
United StatesNoch nicht rekrutierend» Google-Maps
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40207 Louisville
United StatesNoch nicht rekrutierend» Google-Maps
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70808 Baton Rouge
United StatesNoch nicht rekrutierend» Google-Maps
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70809 Baton Rouge
United StatesNoch nicht rekrutierend» Google-Maps
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21215 Baltimore
United StatesNoch nicht rekrutierend» Google-Maps
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21044 Columbia
United StatesNoch nicht rekrutierend» Google-Maps
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02111 Boston
United StatesNoch nicht rekrutierend» Google-Maps
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01655 Worcester
United StatesNoch nicht rekrutierend» Google-Maps
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48201 Detroit
United StatesNoch nicht rekrutierend» Google-Maps
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49503 Grand Rapids
United StatesNoch nicht rekrutierend» Google-Maps
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55109 Saint Paul
United StatesNoch nicht rekrutierend» Google-Maps
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63129 Saint Louis
United StatesNoch nicht rekrutierend» Google-Maps
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87109 Albuquerque
United StatesNoch nicht rekrutierend» Google-Maps
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12206 Albany
United StatesNoch nicht rekrutierend» Google-Maps
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10065 New York
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
11794-7263 Stony Brook
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
45219 Cincinnati
United StatesNoch nicht rekrutierend» Google-Maps
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45245 Cincinnati
United StatesNoch nicht rekrutierend» Google-Maps
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02903 Providence
United StatesNoch nicht rekrutierend» Google-Maps
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37203 Nashville
United StatesNoch nicht rekrutierend» Google-Maps
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75230 Dallas
United StatesNoch nicht rekrutierend» Google-Maps
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75246 Dallas
United StatesNoch nicht rekrutierend» Google-Maps
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75028 Flower Mound
United StatesNoch nicht rekrutierend» Google-Maps
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76104 Fort Worth
United StatesNoch nicht rekrutierend» Google-Maps
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77090 Houston
United StatesNoch nicht rekrutierend» Google-Maps
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77339 Kingwood
United StatesNoch nicht rekrutierend» Google-Maps
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77479 Sugar Land
United StatesNoch nicht rekrutierend» Google-Maps
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22903 Charlottesville
United StatesNoch nicht rekrutierend» Google-Maps
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23114 Midlothian
United StatesNoch nicht rekrutierend» Google-Maps
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23502 Norfolk
United StatesNoch nicht rekrutierend» Google-Maps
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24014 Roanoke
United StatesNoch nicht rekrutierend» Google-Maps
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98405 Tacoma
United StatesNoch nicht rekrutierend» Google-Maps
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53792 Madison
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
C1125ABD Buenos Aires
ArgentinaNoch nicht rekrutierend» Google-Maps
Research Site
C1015ABO Ciudad Autonoma Bs As
ArgentinaNoch nicht rekrutierend» Google-Maps
Research Site
B2900 San Nicolas de Los Arroyos
ArgentinaNoch nicht rekrutierend» Google-Maps
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2050 Camperdown
AustraliaNoch nicht rekrutierend» Google-Maps
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3084 Heidelberg
AustraliaNoch nicht rekrutierend» Google-Maps
Research Site
14784-400 Barretos
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
80730-150 Curitiba
BrazilNoch nicht rekrutierend» Google-Maps
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88034-000 Florianópolis
BrazilNoch nicht rekrutierend» Google-Maps
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74000-000 Goiânia
BrazilNoch nicht rekrutierend» Google-Maps
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90035-003 Porto Alegre
BrazilNoch nicht rekrutierend» Google-Maps
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01246-000 Sao Paulo
BrazilNoch nicht rekrutierend» Google-Maps
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01317-001 São Paulo
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
64049-200 Teresina
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
J4V 2H1 Greenfield Park
CanadaNoch nicht rekrutierend» Google-Maps
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44805 Saint Herblain Cedex
FranceNoch nicht rekrutierend» Google-Maps
Research Site
31059 Toulouse Cedex 9
FranceNoch nicht rekrutierend» Google-Maps
Research Site
54511 Vandoeuvre-lès-nancy
FranceNoch nicht rekrutierend» Google-Maps
Research Site
811-1395 Fukuoka-shi
JapanNoch nicht rekrutierend» Google-Maps
Research Site
960-1295 Fukushima-shi
JapanNoch nicht rekrutierend» Google-Maps
Research Site
350-1298 Hidaka-shi
JapanNoch nicht rekrutierend» Google-Maps
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734-8551 Hiroshima-shi
JapanNoch nicht rekrutierend» Google-Maps
Research Site
362-0806 Kitaadachi-gun
JapanNoch nicht rekrutierend» Google-Maps
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860-8556 Kumamoto-shi
JapanNoch nicht rekrutierend» Google-Maps
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830-0011 Kurume-shi
JapanNoch nicht rekrutierend» Google-Maps
Research Site
791-0280 Matsuyama-shi
JapanNoch nicht rekrutierend» Google-Maps
Research Site
466-8560 Nagoya-shi
JapanNoch nicht rekrutierend» Google-Maps
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951-8566 Niigata-shi
JapanNoch nicht rekrutierend» Google-Maps
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663-8501 Nishinomiya-shi
JapanNoch nicht rekrutierend» Google-Maps
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700-8558 Okayama-shi
JapanNoch nicht rekrutierend» Google-Maps
Research Site
980-8574 Sendai-shi
JapanNoch nicht rekrutierend» Google-Maps
Research Site
160-0023 Shinjuku-ku
JapanNoch nicht rekrutierend» Google-Maps
Research Site
06273 Seoul
Korea, Republic ofNoch nicht rekrutierend» Google-Maps
Research Site
0 3100 Mexico City
MexicoNoch nicht rekrutierend» Google-Maps
Research Site
29090 Tuxtla Gutierrez
MexicoNoch nicht rekrutierend» Google-Maps
Research Site
6000 Cebu City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
1780 Muntinlupa City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
1112 Quezon City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
1502 San Juan
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
7570 Cape Town
South AfricaNoch nicht rekrutierend» Google-Maps
Research Site
2013 Johannesburg
South AfricaNoch nicht rekrutierend» Google-Maps
Research Site
2193 Johannesburg
South AfricaNoch nicht rekrutierend» Google-Maps
Research Site
2196 Johannesburg
South AfricaNoch nicht rekrutierend» Google-Maps
Research Site
0081 Pretoria
South AfricaNoch nicht rekrutierend» Google-Maps
Research Site
08907 Hospitalet deLlobregat
SpainNoch nicht rekrutierend» Google-Maps
Research Site
OX3 7LE Oxford
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
700000 Ho Chi Minh City
VietnamNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

The primary objective of the study is to demonstrate superiority of Dato-DXd + durvalumab

relative to ICC + pembrolizumab by assessment of PFS as assessed by BICR in participants with

PD-L1 positive locally recurrent inoperable or metastatic TNBC.

The study will be stratified based on geographic location (US/Canada/Europe vs. Dato-DXd

monotherapy enrolling countries vs. rest of world), disease-free interval (DFI) history (de

novo vs. prior DFI 6 to 12 months vs. prior DFI > 12 months), and prior PD-1/PD-L1 treatment

for early stage TNBC (yes vs. no).

This study aims to see if Dato-DXd with durvalumab allows patients to live longer without

their breast cancer getting worse, or simply to live longer, compared to patients receiving

standard of care chemotherapy and pembrolizumab. This study is also looking to see how the

treatment and the breast cancer affects patients' quality of life.

Ein-/Ausschlusskriterien

Key Inclusion Criteria

- Histologically or cytologically documented locally recurrent inoperable, which cannot

be treated with curative intent, or metastatic TNBC, as defined by the ASCO-CAP

guidelines.

- ECOG PS 0 or 1.

- All participants must provide a FFPE metastatic or locally recurrent inoperable tumour

sample.

- PD-L1 positive TNBC based on results from an appropriately validated investigational

PD-L1 (22C3) assay (CPS ≥ 10) from a sponsor designated central laboratory.

- No prior chemotherapy or targeted systemic anti-cancer therapy for metastatic or

locally recurrent inoperable breast cancer.

- Patients with recurrent disease will be eligible if they have completed treatment

for Stage I-III breast cancer, if indicated, and ≥6 months have elapsed between

completion of treatment with curative intent and the first documented recurrence.

- Eligible for one of the chemotherapy options listed as ICC (paclitaxel,

nab-paclitaxel, or gemcitabine + carboplatin).

- Measurable disease as per RECIST 1.1.

- Adequate bone marrow reserve and organ function.

- Male and female participants of childbearing potential must agree to use

protocol-specified method(s) of contraception.

Key Exclusion Criteria

- As judged by investigator, severe or uncontrolled medical conditions including

systemic diseases, history of allogeneic organ transplant and active bleeding

diseases, ongoing or active infection, significant cardiac or psychological

conditions.

- History of another primary malignancy except for malignancy treated with curative

intent with no known active disease within 3 years before Cycle 1 Day 1 and of low

potential risk for recurrence.

- Neoplastic spinal cord compression or active brain metastases, leptomeningeal

carcinomatosis or history of leptomeningeal carcinomatosis.

- Participants with treated clinically inactive brain metastases that are no longer

symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be

included in the study if they have recovered from acute toxic effects of radiotherapy.

- Uncontrolled infection requiring IV antibiotics, antivirals or antifungals.

- Active or uncontrolled hepatitis B or C virus infection.

- Known HIV infection that is not well controlled.

- Uncontrolled or significant cardiac disease.

- History of non-infectious ILD/pneumonitis (including radiation pneumonitis) that

required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot

be ruled out by imaging at screening.

- Severe pulmonary function compromise.

- Clinically significant corneal disease.

- Active or prior documented autoimmune or inflammatory disorders.

- Prior exposure to any treatment including ADC containing a chemotherapeutic agent

targeting topoisomerase I and TROP2-targeted therapy.

- Any concurrent anti-cancer treatment.

- Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors or

Dato-DXd.

- Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning

to become pregnant.

Studien-Rationale

Primary outcome:

1. Progression Free Survival (PFS) (Time Frame - From randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause (anticipated to be up to 33 months).):
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anticancer therapy or clinically progresses prior to RECIST 1.1 progression. However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits. The measure of interest is the HR of PFS.



Secondary outcome:

1. Overall Survival (OS) (Time Frame - From randomisation until the date of death due to any cause (anticipated to be up to 64 months).):
OS is defined as the time from randomisation until the date of death due to any cause.

2. Objective Response Rate (ORR) (Time Frame - From randomisation up until progression (anticipated to be up to 33 months).):
ORR is defined as the proportion of participants who have a CR or PR, as determined by the BICR/investigator assessment, per RECIST 1.1.

3. Duration of Response (DoR) (Time Frame - From the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause (anticipated to be up to 33 months).):
DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause.

4. Progression-Free Survival (PFS) by Investigator assessment (Time Frame - From randomisation until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause (anticipated to be up to 33 months).):
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause.

5. Clinical Benefit Rate (CBR) at 24 weeks (Time Frame - From randomisation up until progression, or the last evaluable assessment in the absence of progression (anticipated to be up to 33 months).):
CBR at 24 weeks is defined as the percentage of participants who have a CR or PR or who have SD, per RECIST 1.1, as assessed by BICR/per investigator assessment and derived from the raw tumour data for at least 23 weeks after randomisation.

6. Time to deterioration (TTD) in breast and arm symptoms in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab (Time Frame - From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression).):
TTD in breast symptoms and arm symptoms as measured by the arm symptoms scale from EORTC IL116 TTD is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold.

7. Time to deterioration (TTD) in pain in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab (Time Frame - Time from the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression).):
TTD in pain as measured by the EORTC IL199.

8. Time to deterioration (TTD) in physical functioning in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab (Time Frame - From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression).):
TTD in physical function as measured by the PROMIS Short Form v2.0 - Physical Function 8c.

9. Time to deterioration (TTD) in GHS/QoL in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab (Time Frame - From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression).):
TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172.

10. Time to First Subsequent Therapy (TFST) (Time Frame - From randomisation until the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment, or death due to any cause (anticipated to be up to 64 months).):
TFST is defined as the time from randomisation until the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment, or death due to any cause.

11. Time to Second Subsequent Therapy (TSST) (Time Frame - From randomisation until the start date of the second subsequent anti cancer therapy after discontinuation of first subsequent treatment, or death due to any cause (anticipated to be up to 64 months).):
TSST is defined as the time from randomisation until the start date of the second subsequent anticancer therapy after discontinuation of first subsequent treatment, or death due to any cause.

12. Progression Free Survival 2 (PFS2) (Time Frame - From the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy, or death (anticipated to be up to 64 months).):
PFS2 will be defined as the time from the randomisation to the earliest progression event (following the initial progression), subsequent to first subsequent therapy, or death. The date of second progression will be recorded by the investigator in the eCRF and defined according to local standard clinical practice based on radiological or clinical progression.

13. Pharmacokinetics of Dato-DXd in combination with durvalumab (Time Frame - From first dose to end of treatment (anticipated to be up to 33 months).):
Concentration of Dato-DXd, total anti-TROP2 antibody, and DXd (payload) in plasma.

14. Immunogenicity of Dato-DXd in combination with durvalumab (Time Frame - From first dose to end of treatment safety follow-up (anticipated to be up to 33 months).):
Presence of antidrug antibodies for Dato-DXd (confirmatory results: positive or negative, titres).

15. Safety and tolerability of Dato-DXd + durvalumab as compared with ICC + pembrolizumab (Time Frame - From first dose to end of treatment safety follow-up (anticipated to be up to 33 months).):
Safety and tolerability will be evaluated in the safety population in terms of AEs.

Studien-Arme

  • Experimental: Dato-DXd + durvalumab
    Arm 1: Dato-DXd + durvalumab
  • Active Comparator: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab
    Arm 2: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin)
  • Experimental: Dato-DXd
    Arm 3: Dato-DXd

Geprüfte Regime

  • Dato-DXd (Datopotamab deruxtecan (Dato-DXd, DS-1062a)):
    Provided in 100mg vials. IV infusion. Experimental drug.
  • Durvalumab (MEDI4736):
    Provided in 500mg vials. IV infusion. Experimental drug.
  • Paclitaxel:
    IV infusion. Active comparator.
  • Nab-paclitaxel:
    IV infusion. Active comparator.
  • Gemcitabine:
    IV infusion. Active comparator.
  • Carboplatin:
    IV infusion. Active comparator.
  • Pembrolizumab:
    IV infusion. Active comparator.

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer"

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