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A Phase 2 Basket Study of Tucatinib in Combination with Trastuzumab in Subjects with Previously Treated, Locally Advanced Unresectable or Metastatic Solid Tumors Driven by HER2 Alterations

Phase 2
Not yet recruiting
Conditions
Metastasis
Solid Tumor
10027655
Registration Number
NL-OMON51882
Lead Sponsor
niversitair Medisch Centrum
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Pending
Sex
Not specified
Target Recruitment
10
Inclusion Criteria

1. Histologically or cytologically confirmed diagnosis of locally-advanced
unresectable or metastatic solid tumor, including primary brain tumors
2. Subjects with disease types other than breast cancer, biliary tract cancer,
non-squamous NSCLC, and cervical cancer: Disease progression on or after the
most recent systemic therapy for locally-advanced unresectable or metastatic
disease
3. Subjects with any breast cancer subtype:
a. Must have HER2-mutated disease which does not display HER2
overexpression/amplification
b. Must have progressed on or after >=1 prior line of treatment (chemotherapy,
endocrine therapy, or targeted therapy) for locally-advanced unresectable or
metastatic breast cancer
c. Subjects with metastatic HR+ HER2-mutated disease must have received a prior
CDK4/6 inhibitor in the metastatic setting
4. Subjects with biliary tract cancer: must have progressed on or after >=1
prior line of treatment (chemotherapy, endocrine therapy, or targeted therapy)
5. Subjects with non-squamous NSCLC: has relapsed from or is refractory to
standard treatment or for which no standard treatment is available
6. Subjects with cervical cancer:
a. Subjects with metastatic cervical cancer must have progressed on or after >=1
prior line of systemic therapy (platinum-based chemotherapy with or without
bevacizumab) in the metastatic setting
b. Subjects with locally advanced unresectable cervical cancer must have
progressed on or after >=1 prior lines of systemic therapy
7. Disease demonstrating HER2 alterations (overexpression/amplification or HER2
activating mutations), as determined by local or central testing processed in a
Clinical Laboratory Improvement Amendments (CLIA)- or International
Organization for Standardization (ISO) accredited laboratory, according to one
of the following:
a. HER2 overexpression/amplification from fresh or archival tumor tissue or
blood utilizing one of the following tests, in subjects with tumor types other
than breast cancer, GEC, or CRC:
i. HER2 overexpression (3+ immunohistochemistry IHC) (breast or gastric
algorithms)
ii. HER2 amplification by in situ hybridization assay (fluorescence in situ
hybridization [FISH] or chromogenic in situ hybridization signal ratio >=2.0 or
gene copy number >6)
iii. HER2 amplification in tissue by next generation sequencing (NGS) assay
iv. HER2 amplification in circulating tumor DNA (ctDNA) by blood-based NGS assay
b. Known activating HER2 mutations detected in fresh or archival tumor tissue
or blood by NGS assay, including:
o Extracellular domain: G309A/E; S310F/Y; C311R/S; C334S
o Kinase domain: T733I; L755P/S; I767M; L768S; D769N/Y/H; Y772; A775; G776;
V777L/M; G778; T798; L841V, V842I; N857S, T862A, L869R, H878Y, R896C
o Transmembrane/juxtamembrane domain: S653C, I655V; V659E; G660D; R678Q; V697.
o Subjects with HER2 activating mutations not listed above may be eligible, if
supported by scientific literature and approved by the medical monitor
8. Have measurable disease per RECIST v1.1 criteria according to investigator
assessment
9. Be at least 18 years of age at time of consent, or considered an adult by
local regulations
10. Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
11. Have a life expectancy of at least 3 months, in the opinion of the
investigator
12.

Exclusion Criteria

1. Subjects with breast cancer, GEC, or CRC whose disease shows HER2
amplification/overexpression.
2. Previous treatment with HER2-directed therapy; subjects with uterine serous
carcinoma may have received prior trastuzumab
3. Known hypersensitivity to any component of the drug formulation of tucatinib
or trastuzumab (drug substance, excipients, murine proteins), or any component
of the drug formulation of fulvestrant in subjects with HR+ HER2-mutated breast
cancer
4. History of exposure to a >360 mg/m² doxorubicin-equivalent or >720 mg/m²
epirubicin-equivalent cumulative dose of anthracyclines
5. Treatment with any systemic anti-cancer therapy, radiation therapy, or
experimental agent within <=3 weeks of first dose of study treatment or are
currently participating in another interventional clinical trial.
6. Have any toxicity related to prior cancer therapies that has not resolved to
<= Grade 1, with the following exceptions:
a. Alopecia
b. Congestive heart failure (CHF), which must have been <= Grade 1 in severity
at the time of occurrence, and must have resolved completely
c. Anemia, which must have resolved to <= Grade 2
7. Have clinically significant cardiopulmonary disease such as:
a. Ventricular arrhythmia requiring therapy
b. Symptomatic hypertension or uncontrolled hypertension as determined by
investigator
c. Any history of symptomatic CHF
d. Severe dyspnea at rest (National Cancer Institute Common Terminology
Criteria for Adverse Events [NCI CTCAE] Grade 3 or above) due to complications
of advanced malignancy
e. Hypoxia requiring supplementary oxygen therapy except when oxygen therapy is
needed only for obstructive sleep apnea
8. Have known myocardial infarction or unstable angina within 6 months prior to
first dose of study treatment
9. Known to be positive for hepatitis B by surface antigen expression. Known to
be positive for hepatitis C infection (positive by polymerase chain reaction).
Subjects who have been treated for hepatitis C infection are permitted if they
have documented sustained virologic response of 12 weeks
10. Presence of known chronic liver disease
11. Subjects known to be positive for human immunodeficiency virus (HIV) are
excluded if they meet any of the following criteria:
• CD4+ T-cell count of <350 cells/µL
• Detectable HIV viral load
• History of an opportunistic infection within the past 12 months
• On stable antiretroviral therapy for <4 weeks
12. Are pregnant, breastfeeding, or planning a pregnancy from time of informed
consent until 7 months after the final dose of any study drug, and, if
applicable, for at least 2 years after the final dose of fulvestrant
13. Have inability to swallow pills
14. Have used a strong cytochrome P450 (CYP) 2C8 inhibitor within 5 half-lives
of the inhibitor, or have used a strong CYP3A4 or CYP2C8 inducer within 5 days
prior to start of treatment
15. Have any other medical, social, or psychosocial factors that, in the
opinion of the investigator, could impact safety or compliance with study
procedures
16. History of another malignancy within 2 years prior to screening, with the
exception of those with a negligible risk of metastasis or death (eg, 5-year OS
of >=90%), such as adequately treated carcinoma in situ of the cervix,
non-melanoma skin carcinoma, localized prostate canc

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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