DB-08: A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer
Study Details
Study Description
Brief Summary
DESTINY-Breast 08 will investigate the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies in patients with Metastatic HER2-low Advanced or Metastatic Breast Cancer
Condition or Disease | Intervention/Treatment | Phase |
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|
Phase 1 |
Detailed Description
This study is modular in design allowing assessment of the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies. Combination-treatment modules will have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the Part 2 dose-expansion phase will use the RP2D determined in Part 1.
The target population of interest in this study is patients with HER2-low (IHC 1+ or IHC 2+/ISH -) (as per ASCO/CAP 2018 guidelines) advanced/MBC. Part 1 of each module will enroll patients with locally confirmed HER2-low advanced/MBC in second-line or later (≥ 2L) settings
Part 2 of each module will enroll patients with HER2-low MBC who have either not received prior treatment, or received only 1 prior treatment (depending on the module-specific exclusion criteria) for advanced/metastatic disease
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Module 1: T-DXd + capecitabine T-DXd: 5.4 mg/kg Q3W, intravenous use Capecitabine: 1000mg/m2 BID, days 1-14 Q3W, oral use |
Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Names:
Drug: Capecitabine
Capecitabine: administered orally
|
Experimental: Module 2: T-DXd + durvalumab + paclitaxel T-DXd: 5.4 mg/kg Q3W, intravenous use Durvalumab: 1120 mg Q3W, intravenous use Paclitaxel: 80 mg/m2 QW in 3-week cycles, intravenous use |
Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Names:
Drug: Durvalumab
Durvalumab: administered as an IV infusion
Other Names:
Drug: Paclitaxel
Paclitaxel: administered as an IV infusion
Other Names:
|
Experimental: Module 3: T-DXd + capivasertib T-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use |
Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Names:
Drug: Capivasertib
Capivasertib: administered orally
Other Names:
|
Experimental: Module 4: T-DXd + anastrozole T-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral |
Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Names:
Drug: Anastrozole
Anastrozole: administered orally
Other Names:
|
Experimental: Module 5: T-DXd + fulvestrant T-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use |
Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Names:
Drug: Fulvestrant
Fulvestrant: administered as an IM injection
|
Outcome Measures
Primary Outcome Measures
- Occurrence of adverse events (AEs)- Part 1 [Up to follow-up period, approximately 24 months]
Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0
- Occurrence of serious adverse events (SAEs)- Part 1 [Up to follow-up period, approximately 24 months]
Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0
- Occurrence of adverse events (AEs)- Part 2 [Up to follow-up period, approximately 24 months]
Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0
- Occurrence of serious adverse events (SAEs)- Part 2 [Up to follow-up period, approximately 24 months]
Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0
Secondary Outcome Measures
- Objective Response Rate (ORR)- Part 2 [Until progression, assessed up to approximately 24 months]
ORR defined as the proportion of patients who have a confirmed CR or PR, as determined by the investigator at local site per RECIST 1.1
- Progression Free Survival (PFS)- Part 2 [Until progression or death, assessed up to approximately 24 months]
PFS defined as time from the date of first dose until the date of progression as determined by the investigator at local site per RECIST 1.1, or death due to any cause
- Duration of Response (DoR)- Part 2 [Until progression or death, assessed up to approximately 24 months]
DoR defined as time from the date of first documented response (which is subsequently confirmed) until the date of documented progression or death in the absence of disease progression
- Overall Survival (OS)- Part 2 [Until death, assessed up to approximately 24 months]
OS defined as time from the date of first dose until the date of death by any cause
- Serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a [While on study drug up to study completion, approximately 24 months]
Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
- Immunogenicity of trastuzumab deruxtecan [Up to follow-up period, approximately 24 months]
Percentage of patients who develop ADA for trastuzumab deruxtecan
- Serum Concentration of durvalumab [While on study drug up to study completion, approximately 24 months]
Determination of durvalumab concentration in serum at different time points after administration
- Immunogenicity of durvalumab [Up to follow-up period, approximately 24 months]
Percentage of patients who develop ADAs for durvalumab
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Patients must be at least 18 years of age
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Male or female patients who have pathologically documented breast cancer that:
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Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay
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Is documented as HR+ (either ER and/or PgR positive [ER or PgR ≥1%]) or ER and PgR negative (ER and PgR <1%) per ASCO/CAP guidelines in the metastatic setting
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Patient must have adequate tumor sample for biomarker assessment
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ECOG Performance Status of 0 or 1
For patients with HR+ disease:
Part 1: At least 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors), and at least 1 prior line of chemotherapy for MBC are required.
Part 2: Only 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors) for MBC is allowed. No prior chemotherapy in the metastatic setting is allowed. Note there are no patients with HR+ disease in Part 2 of Modules 2 and 3.
For patients with HR- disease:
Part 1: At least 1 prior line of chemotherapy for MBC is required. Note there are no patients with HR- disease in Part 1 of Modules 4 and 5.
Part 2: For Module 2, no prior lines of therapy for MBC are allowed, and for Modules 1 and 3, only 1 prior line of chemotherapy for MBC is allowed. Note there are no patients with HR- disease in Part 2 of Modules 4 and 5.
Key Exclusion Criteria:
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Uncontrolled intercurrent illness
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Uncontrolled or siginificant cardiovascular disease
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History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
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Lung-specific intercurrent clinically significant illnesses
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Has spinal cord compression or clinically active central nervous system metastases
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Active primary immunodeficiency
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Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
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Prior treatment with ADC that comprises of an exatecan derivative that is a topoisomerase I inhibitor.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Research Site | Iowa City | Iowa | United States | 52242 |
2 | Research Site | Minneapolis | Minnesota | United States | 55426 |
3 | Research Site | Saint Paul | Minnesota | United States | 55101 |
4 | Research Site | Basking Ridge | New Jersey | United States | 07920 |
5 | Research Site | Middletown | New Jersey | United States | 07748 |
6 | Research Site | Montvale | New Jersey | United States | 07645 |
7 | Research Site | Ridgewood | New Jersey | United States | 07450 |
8 | Research Site | Commack | New York | United States | 11725 |
9 | Research Site | Harrison | New York | United States | 10604 |
10 | Research Site | Long Island City | New York | United States | 11101 |
11 | Research Site | New York | New York | United States | 10011 |
12 | Research Site | New York | New York | United States | 10019 |
13 | Research Site | New York | New York | United States | 10029 |
14 | Research Site | New York | New York | United States | 10065 |
15 | Research Site | Uniondale | New York | United States | 11553 |
16 | Research Site | Chapel Hill | North Carolina | United States | 27514 |
17 | Research Site | Portland | Oregon | United States | 97239 |
18 | Research Site | Chattanooga | Tennessee | United States | 37404 |
19 | Research Site | Germantown | Tennessee | United States | 38138 |
20 | Research Site | Fort Worth | Texas | United States | 76104 |
21 | Research Site | East Melbourne | Australia | 3002 | |
22 | Research Site | Westmead | Australia | 2145 | |
23 | Research Site | Anderlecht | Belgium | 1070 | |
24 | Research Site | Antwerpen | Belgium | 2020 | |
25 | Research Site | Edegem | Belgium | 2650 | |
26 | Research Site | Leuven | Belgium | 3000 | |
27 | Research Site | Ottignies | Belgium | 1340 | |
28 | Research Site | Brasília | Brazil | 70200-730 | |
29 | Research Site | Florianópolis | Brazil | 88034-000 | |
30 | Research Site | Goiania | Brazil | 74605-070 | |
31 | Research Site | Porto Alegre | Brazil | 90035-003 | |
32 | Research Site | Porto Alegre | Brazil | 90110-270 | |
33 | Research Site | Sao Paulo | Brazil | 01317-001 | |
34 | Research Site | Sao Paulo | Brazil | 04543-000 | |
35 | Research Site | São Paulo | Brazil | 03102-002 | |
36 | Research Site | São Paulo | Brazil | 04538-132 | |
37 | Research Site | Kelowna | British Columbia | Canada | V1Y 5L3 |
38 | Research Site | Quebec | Canada | G1J 1Z4 | |
39 | Research Site | Villejuif Cedex | France | 94805 | |
40 | Research Site | Seoul | Korea, Republic of | 03080 | |
41 | Research Site | Seoul | Korea, Republic of | 03722 | |
42 | Research Site | Seoul | Korea, Republic of | 05505 | |
43 | Research Site | Seoul | Korea, Republic of | 06351 | |
44 | Research Site | Culiacán | Mexico | 80230 | |
45 | Research Site | La Paz | Mexico | 23040 | |
46 | Research Site | Merida | Mexico | 97000 | |
47 | Research Site | Monterrey | Mexico | 64710 | |
48 | Research Site | Moscow | Russian Federation | 115478 | |
49 | Research Site | Moscow | Russian Federation | 143442 | |
50 | Research Site | Saint Petersburg | Russian Federation | 194017 | |
51 | Research Site | Saint Petersburg | Russian Federation | 195271 | |
52 | Research Site | Saint Petersburg | Russian Federation | 199226 | |
53 | Research Site | Saint-Petersburg | Russian Federation | 197758 | |
54 | Research Site | Kaohsiung | Taiwan | 82445 | |
55 | Research Site | Taichung | Taiwan | 40443 | |
56 | Research Site | Taipei City | Taiwan | 114 | |
57 | Research Site | Taipei | Taiwan | 100 | |
58 | Research Site | Taipei | Taiwan | 11217 | |
59 | Research Site | Taipei | Taiwan | 235 | |
60 | Research Site | Taoyuan | Taiwan | 333 |
Sponsors and Collaborators
- AstraZeneca
- Daiichi Sankyo Co., Ltd.
- Daiichi Sankyo Company, Limited
Investigators
- Principal Investigator: Komal Jhaveri, MD, FACP, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- D967JC00002