Advanced/Metastatic HER2-Positive Breast Cancer
Trastuzumab deruxtecan (T-DXd, AZD4552)
To describe the overall treatment effect of T-DXd in HER2-positive Metastatic HER2-Positive Breast Cancer patients with or without baseline brain metastasis
1 Participant must be ≥ 18 years at the time of screening.
2 Pathologically documented breast cancer that:
(a) Is unresectable/advanced or metastatic, and
(b) Has confirmed HER2-positive status as determined according to ASCO/CAP guidelines (Wolff et al, 2018) evaluated at a local laboratory
3 Participant must have either:
(a) No evidence of BM, or
(b) Untreated BM on screening contrast brain MRI / CT scan
(i) not needing immediate local therapy, or
(ii) For participants with untreated CNS lesions > 2.0 cm, discussion with and approval from the study physician is required prior to enrollment, or
(c) Previously-treated stable or progressing BM
(i) Previously-treated BM with local therapy may either be radiographically stable for ≥ 4 weeks since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy
1 Known or suspected LMD.
2 Prior exposure to tucatinib treatment
3 As judged by the investigator, any evidence of diseases substantially increase risk of incurring AEs, which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or would jeopardize compliance with the protocol
4 Refractory nausea and vomiting, chronic gastrointestinal disease, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of T-DXd
5 History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence.
6 Persistent toxicities (CTCAE Grade >1) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention (eg, hearing loss) may be included after consultation with the AstraZeneca study physician.
7 Based on screening contrast brain MRI / CT scan, participants must not have any of the following:
(a) Any untreated brain lesions > 2.0 cm in size, unless discussed with the study physician and approval is given
(b) Ongoing use of systemic corticosteroids for control of symptoms of BMs at a total daily dose of > 2 mg of dexamethasone (or equivalent). However, participants on a
chronic stable dose of ≤ 2 mg total daily of dexamethasone (or equivalent) may be eligible with discussion and approval by the study physician.
(c) Any brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatmentrelated
edema may pose risk to participant (eg, brain stem lesions). Participants who undergo local treatment for such lesions identified by screening contrast brain MRI /
CT scan may still be eligible for the study based on criteria described under CNS inclusion criteria 3 and 5.
(d) Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to BMs notwithstanding CNS-directed therapy
8 Has spinal cord compression
9 Known active hepatitis B or C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1. Participants with past or resolved HBV
infection are eligible, if negative for HBsAg and positive for anti-HBc. Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
10 Active primary immunodeficiency, known to have tested positive for HIV
11 Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
12 Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd
13 Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with participation in the clinical study or evaluation of the clinical study results