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JOURNAL ONKOLOGIE – STUDIE

A Study of Dato-DXd With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Without Pathological Complete Response Following Neoadjuvant Therapy (TROPION-Breast03)

Rekrutierend

NCT-Nummer:
NCT05629585

Studienbeginn:
November 2022

Letztes Update:
09.04.2024

Wirkstoff:
Dato-DXd, Durvalumab, Capecitabine, Pembrolizumab

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
AstraZeneca

Collaborator:
Daiichi Sankyo, SWOG Clinical Trials Partnerships,

Studienleiter

Aditya Bardia, MD, MPH
Study Chair
Massachusetts General Hospital

Kontakt

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

Studienlocations
(3 von 363)

Research Site
65929 Frankfurt am Main
(Hessen)
GermanyRekrutierend» Google-Maps
Research Site
30177 Hannover
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Research Site
74078 Heilbronn
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
24105 Kiel
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Research Site
71640 Ludwigsburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
41061 Mönchengladbach
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
33098 Paderborn
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
70199 Stuttgart
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
53840 Troisdorf
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
58452 Witten
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
42283 Wuppertal
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
71913 Hot Springs National Park
United StatesRekrutierend» Google-Maps
Research Site
92653 Laguna Hills
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
92354 Loma Linda
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
90806 Long Beach
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
90024 Los Angeles
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
92663 Newport Beach
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
94611 Oakland
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
92868 Orange
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
95661 Roseville
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
94115 San Francisco
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
95051 Santa Clara
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
94589 Vallejo
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
94596 Walnut Creek
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
90048 West Hollywood
United StatesZurückgezogen» Google-Maps
Research Site
32701 Altamonte Springs
United StatesRekrutierend» Google-Maps
Research Site
33140 Miami Beach
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
33705 Saint Petersburg
United StatesRekrutierend» Google-Maps
Research Site
30607 Athens
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
60005 Arlington Heights
United StatesRekrutierend» Google-Maps
Research Site
60611 Chicago
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
62526 Decatur
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
60153 Maywood
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
21201 Baltimore
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
48109 Ann Arbor
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
08816 East Brunswick
United StatesZurückgezogen» Google-Maps
Research Site
07450 Ridgewood
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
87109 Albuquerque
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
10549 Mount Kisco
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
10029 New York
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
10591 Sleepy Hollow
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
16335 Meadville
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
29169 West Columbia
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
37232 Nashville
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
75251 Dallas
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
77030 Houston
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
41253-190 Salvador
BrazilAktiv, nicht rekrutierend» Google-Maps
Research Site
01508-010 Sao Paulo
BrazilAktiv, nicht rekrutierend» Google-Maps
Research Site
54639 Thessaloniki
GreeceNoch nicht rekrutierend» Google-Maps
Research Site
463-712 Seongnam-Si
Korea, Republic ofRekrutierend» Google-Maps
Research Site
00918 San Juan
Puerto RicoNoch nicht rekrutierend» Google-Maps
Research Site
SW3 6JJ Greater London
United KingdomRekrutierend» Google-Maps
Research Site
NE7 7AF Newcastle upon Tyne
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

The study will investigate the efficacy and safety of Dato-DXd with or without durvalumab

when compared with ICT (capecitabine and/or pembrolizumab) in participants with stage I to

III TNBC who have residual invasive disease in the breast and/or axillary lymph nodes at

surgical resection following neoadjuvant systemic therapy.

The primary objective of the study is to demonstrate superiority of Dato-DXd in combination

with durvalumab relative to ICT by assessment of iDFS in participants with stage I to III

TNBC with residual invasive disease at surgical resection following neoadjuvant therapy.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Participant must be ≥ 18 years at the time of screening.

2. Histologically confirmed invasive TNBC, as defined by the ASCO/CAP guidelines.

3. Residual invasive disease in the breast and/or axillary lymph node(s) at surgical

resection following neoadjuvant therapy.

4. Completed at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or

a taxane with or without platinum chemotherapy, with or without pembrolizumab.

5. No evidence of locoregional or distant relapse.

6. Surgical removal of all clinically evident disease in the breast and lymph nodes.

7. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks

prior to randomisation.

8. All participants must provide an FFPE tumour sample from residual invasive disease at

surgery for tissue-based analysis.

9. No adjuvant systemic therapy.

10. Radiotherapy (if indicated) delivered before the start of study intervention.

11. If post-operative radiation therapy is given, an interval of no more than 6 weeks

between the completion of radiation therapy and the date of randomisation (radiation

therapy can be completed during screening period). If no post-operative radiation

therapy is given, an interval of no more than 16 weeks between the date of breast

surgery and the date of randomisation.

12. Has LVEF ≥ 50% by either an ECHO or MUGA scan within 28 days before randomisation.

13. Eligible for one of the therapy options listed as investigator's choice per

investigator assessment.

14. No known germline BRCA1 or BRCA2 pathogenic mutation.

15. Adequate bone marrow reserve and organ function within 7 days before randomisation.

Exclusion Criteria:

1. Stage IV (metastatic) TNBC.

2. History of prior invasive breast cancer, or evidence of recurrent disease following

preoperative therapy and surgery.

3. Severe or uncontrolled medical conditions including systemic diseases, history of

allogeneic organ transplant and active bleeding diseases, ongoing or active infection,

serious chronic gastrointestinal conditions associated with diarrhea chronic

diverticulitis or previous complicated diverticulitis.

4. History of another primary malignancy except for adequately resected basal cell

carcinoma of the skin or squamous cell carcinoma of the skin, in situ disease

(including ductal carcinoma in situ) that has undergone potentially curative therapy,

or other solid malignancy treated with curative intent with no known active disease

within 5 years before randomisation and of low potential risk for recurrence.

5. Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not

yet improved to Grade ≤ 1 or baseline. Participants with irreversible toxicity that is

not reasonably expected to be exacerbated by study intervention may be included (eg,

hearing loss).

6. Active or prior documented autoimmune or inflammatory disorders.

7. Clinically significant corneal disease.

8. Active or uncontrolled hepatitis B or C virus infection.

9. Known HIV infection that is not well controlled

10. Active tuberculosis infection.

11. Mean resting corrected QTcF > 470 ms regardless of gender, obtained from triplicate

12-lead ECGs performed at screening.

12. Uncontrolled or significant cardiac disease.

13. History of non-infectious ILD/pneumonitis including radiation, pneumonitis that

required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that

cannot be ruled out by imaging at screening.

14. Has severe pulmonary function compromise.

15. Any known active liver disease.

16. Grade ≥ 2 peripheral neuropathy of any aetiology.

17. Prior exposure to a PD-1/PD-L1 inhibitor other than pembrolizumab.

18. Current or prior use of immunosuppressive medication within 14 days prior to

randomisation.

19. Participants with a known severe hypersensitivity to Dato-DXd or any of the excipients

of these products including but not limited to polysorbate 80 or other monoclonal

antibodies.

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

21. Participation in another clinical study with a study intervention or investigational

medicinal device administered in the last 4 weeks prior to randomisation,

randomisation into a prior Dato-DXd, T-DXd, or durvalumab study regardless of

treatment assignment.

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

to become pregnant.

Studien-Rationale

Primary outcome:

1. Invasive disease-free survival (iDFS) for Dato-DXd + durvalumab vs. ICT (Time Frame - From randomisation to date of the event, up to 57 months from first subject in):
iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause. iDFS will be determined based on disease recurrence per investigator assessment based on all available clinical assessments. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest will be the HR (hazard ratio) of iDFS for Dato-DXd + durvalumab vs ICT.



Secondary outcome:

1. Distant disease-free survival (DDFS) for Dato-DXd + durvalumab vs ICT (Time Frame - From randomisation to date of the event, up to 57 months from first subject in):
DDFS is defined as time from randomisation to date of first distant recurrence, occurrence of second primary non-breast invasive cancer, or death from any cause. DDFS is determined based on disease recurrence per investigators assessment based on all available clinical assessments. The analysis will include all randomised participants, as randomised regardless of whether the participant withdraws from randomised therapy or received another anticancer therapy. The measure of interest will be the HR (hazard ratio) of DDFS for Dato-DXd + durvalumab vs ICT.

2. DDFS for Dato-DXd vs ICT (Time Frame - From randomisation to date of the event, up to 57 months from first subject in):
DDFS is defined as time from randomisation to date of first distant recurrence, occurrence of second primary non-breast invasive cancer, or death from any cause. DDFS is determined based on disease recurrence per investigators assessment based on all available clinical assessments. The measure of interest will be the HR (hazard ratio) of DDFS for Dato-DXd vs ICT.

3. DDFS for Dato-DXd + durvalumab vs Dato-DXd (Time Frame - From randomisation to date of the event, up 57 months from first subject in):
DDFS is defined as time from randomisation to date of first distant recurrence, occurrence of second primary non-breast invasive cancer, or death from any cause. DDFS is determined based on disease recurrence per investigators assessment based on all available clinical assessments. The measure of interest will be the HR (hazard ratio) of DDFS for Dato-DXd + durvalumab vs Dato-DXd.

4. Overall Survival (OS) for Dato-DXd + durvalumab vs ICT (Time Frame - From randomisation to date of death, due to any cause, up to 87 months from first subject in):
OS is defined as time from randomisation until date of death due to any cause. The analysis will include all randomised participants, as randomised regardless of whether the participant withdraws from randomised therapy or received another anticancer therapy. The measure of interest will be the HR (hazard ratio) of OS for Dato-DXd + durvalumab vs ICT.

5. OS for Dato-DXd vs ICT (Time Frame - From randomisation to date of death, due to any cause, up to 87 months from first subject in):
OS is defined as time from randomisation until date of death due to any cause. The measure of interest will be the HR (hazard ratio) of OS for Dato-DXd vs ICT.

6. iDFS for Dato-DXd vs ICT (Time Frame - From randomisation to date of the event, up to 57 months from first subject in):
iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause. iDFS will be determined based on disease recurrence per investigator assessment based on all available clinical assessments. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest will be the HR (hazard ratio) of iDFS for Dato-DXd vs ICT.

7. iDFS for Dato-DXd + durvalumab vs Dato-DXd (Time Frame - From randomisation to date of the event, up to 57 months from first subject in):
iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause. The measure of interest will be the HR (hazard ratio) of iDFS for Dato-DXd + durvalumab vs Dato-DXd.

8. Participant-reported physical function in participants treated with Dato-DXd with or without durvalumab compared with ICT (Time Frame - From randomisation to date of the deterioration, up to 36 months after randomisation):
Time to Deterioration (TTD) and actual scores in physical function as measured by the PROMIS Physical Function Short Form 8c.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. The analysis will include all dosed participants. The measure of interest is the HR (hazard ratio) of TTD and mean between-arm difference in physical function for Dato-DXd with or without durvalumab compared with ICT.

9. Participant-reported in GHS/QoL in participants treated with Dato-DXd with or without durvalumab compared with ICT (Time Frame - From randomisation to date of the deterioration, up to 36 months after randomisation):
Time to Deterioration (TTD) and actual scores in GHS/QoL as measured by the GHS/QoL scale from the EORTC IL172. 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. The analysis will include all randomised participants. The measure of interest is the HR (hazard ratio) of TTD and mean between-arm difference in GHS/QoL for Dato-DXd with or without durvalumab compared with ICT.

10. Participant-reported fatigue in participants treated with Dato-DXd with or without durvalumab compared with ICT (Time Frame - From randomisation to 24 months after randomisation):
Proportion of participants experiencing different levels of fatigue at 3 months (13weeks), 6 months (26 weeks), and 12 months (52 weeks) as measured by PROMIS Fatigue Short Form 7a. The analysis will include all dosed participants. The measure of interest will be the proportion of participants reporting different levels of fatigue.

11. Pharmacokinetics of Dato-DXd (Time Frame - Day 1 of cycles 1,2,4,6,8 (Each cycle is 21 days)):
Concentration of Dato- DXd, total anti-TROP2 antibody, and MAAA-1181 in plasma.

12. Immunogenicity of Dato-DXd (Time Frame - Day 1 of cycles 1,2,4,6,8 (Each cycle is 21 days) and within 35 days of completion of or discontinuation of study intervention (at an average of 6 months following randomization)):
Presence of ADAs for Dato-DXd (confirmatory results: positive or negative; titres).

13. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) (Time Frame - Randomization to final safety follow-up visit, either 90 days after last dose of study intervention for those who complete planned study intervention or 90 days after date of discontinuation for those who discontinue study intervention prematurely):
Safety and tolerability will be evaluated in terms of AEs (graded by CTCAE version 5.0).

Studien-Arme

  • Experimental: Dato-DXd in combination with Durvalumab
    Arm 1: Dato-DXd 6 mg/kg IV Q3W x 8 cycles + Durvalumab 1120 mg IV Q3W x 9 cycles
  • Experimental: Dato-DXd
    Arm 2: Dato-DXd 6 mg/kg IV Q3W x 8 cycles
  • Active Comparator: Investigators Choice Therapy
    Arm 3: Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles Pembrolizumab* (200 mg IV on Day 1, Q3W) for 9 cycles Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles + pembrolizumab* (200 mg IV on Day 1, Q3W) for 9 cycles * Only participants who have received prior pembrolizumab in the neoadjuvant setting should receive pembrolizumab as part of their adjuvant therapy on Arm 3.

Geprüfte Regime

  • Dato-DXd (Datopotamab deruxtecan (Dato-DXd, DS-1062a)):
    Experimental drug. Provided in 100mg vials. IV infusion
  • Durvalumab (MEDI4736):
    Experimental drug. Provided in 50mg vials. IV infusion
  • Capecitabine (XELODA®, Capecitabine Cell Pharm, Capecitabine EG, Capecitabine Accord):
    Active Comparator. Tablet. Oral route of administration
  • Pembrolizumab (KEYTRUDA®):
    Active Comparator. Provided in 100mg vials. IV infusion

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"A Study of Dato-DXd With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Without Pathological Complete Response Following Neoadjuvant Therapy (TROPION-Breast03)"

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