Brentuximab Vedotin in CD30-Expressing Germ Cell Tumors After Chemotherapy Failure

At present, the prognosis of patients with germ cell tumors (GCTs) in whom multiple chemotherapy regimens have failed is frustratingly dismal, and the few chances of cure have approximated 10%. ^{,  ,  ,}  An average of > 35 years of life is lost when a patient dies of a GCT, well over a decade longer than any other adult malignancy, and this reality underscores the need to identify new active agents against GCTs. Hence, the development of new compounds is awaited, and immunotherapy might provide a window of opportunity to investigate novel compounds in this field to change the therapeutic paradigm of these young adult patients. CD30 is exquisitely expressed by embryonal carcinoma, and its immunohistochemical expression has been reported to have an independent detrimental prognostic effect. Brentuximab vedotin (BV; SGN-35) is an antibody–drug conjugate consisting of the chimeric antibody SGN-30 (cAC10) chemically conjugated to a synthetic analog (monomethyl auristatin E) of the antitubulin agent dolastatin. Reports of clinical activity in GCTs were based on 3 patients enrolled in a phase II trial of BV in multiple CD30-expressing malignancies. We designed a phase II, single-center trial with BV as salvage therapy for advanced-stage and CD30-expressing GCT (ClinicalTrials.gov identifier, NCT01851200): 24 patients received BV 1.8 mg/kg intravenously every 3 weeks until disease progression or the onset of unacceptable toxicity. The eligibility criteria included the failure of ≥ 2 cisplatin-based regimens, including high-dose chemotherapy (HDCT). The availability of archival tumor specimens from the most recent postchemotherapy surgery or tumor biopsy specimens was required for eligibility (see Supplemental Figure 1 in the online version). Only postchemotherapy tumor specimens of metastatic disease (after any line of treatment) were stained for CD30, and the availability of tissue from orchiectomy only was not allowed. Patient tumor samples were prospectively centralized at the study sponsor's institution and assessed for CD30 expression by immunohistochemistry using a prediluted monoclonal mouse antibody (Dako EnVision). All patients underwent measurement of serum tumor markers (STMs) every 3 weeks and radiologic restaging with computed tomography and fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography every 6 weeks (2 cycles). An optimal Simon 2-stage design was applied. The primary endpoint was the objective response rate (H0, ≤ 5%; H1, ≥ 25%; α and β, 10%) according to the Response Evaluation Criteria In Solid Tumors, version 1.1. The results of the first stage of the trial are reported in the present report.