A Phase 1/2 Study of MEDI4276 in Adults Subjects With Select HER2-expressing Advanced Solid Tumors.

Inclusion criteria

• Age ≥ 18 years.
• Histologically or cytologically documented unresectable, locally advanced or metastatic breast cancer or gastric cancer refractory to standard therapy.

• For subjects with breast cancer:

• Prior treatment with trastuzumab, pertuzumab, and T-DM1, either alone or in combination, is required.
• Subjects with a primary tumor that is hormone (estrogen, progesterone, or both) receptor-positive or receptor-negative are eligible.
• Prior hormone therapy is allowed, but last dose must be at least 14 days prior to first dose of MEDI4276.
• For subjects with gastric cancer:

• Prior treatment with a trastuzumab containing chemotherapy regimen is required.
• HER2 Positive disease documented as FISH-positive and/or 3+ by IHC on previously collected tumor tissue.
• At least one lesion measurable by RECIST Version 1.1.

Exclusion criteria

• Receipt of any conventional or investigational anticancer treatment within 28 days prior to the first dose of MEDI4276.
• History of exposure to the following cumulative doses of anthracyclines:

• Doxorubicin or liposomal doxorubicin >350 mg/m².
• Epirubicin >530 mg/m².
• Mitoxantrone >90 mg/m² and idarubicin > 70 mg/m².
• If another anthracycline or more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 350 mg/m² of doxorubicin.
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery or other therapy to control symptoms from brain metastases within 2 months prior to first dose of MEDI4276.