ABSTRACT
PURPOSE: Monalizumab binds CD94/NKG2A, preventing HLA-E inhibition of tumor lymphocytes. A dose-ranging/cohort expansion trial of monalizumab for recurrent gynecologic malignancies was conducted to determine the recommended phase II dose (RP2D) and to explore clinical activity, pharmacokinetics, pharmacodynamics, safety, and immunogenicity. PATIENTS AND METHODS: Participants (and part 2 expansion cohorts) included (i) platinum-sensitive ovarian, (ii) platinum-resistant ovarian, (iii) squamous cervical (CX), and (iv) epithelial endometrial (END) carcinomas. Part 1 assessed monalizumab at 1, 4, or 10 mg/kg every 2 weeks. In part 2, ≥4 patients/cohort underwent pre- and on-treatment tumor biopsies. Preset criteria determined cohort expansion. RESULTS: A total of 58 participants were evaluable. The RP2D was 10 mg/kg i.v. every 2 weeks. Dose proportionality and 100% NKG2A saturation were observed. Related adverse events were mild: headache, abdominal pain, fatigue, nausea, and vomiting. Grade 3 related adverse events were nausea (1), vomiting (1), dehydration (1), fatigue (2), anorexia (1), dyspnea (1), and proctitis (1). Dose-limiting toxicities were not observed. Hematologic and biochemical changes were mild and not dose related. Best response was SD: part 1, 7 of 18 (39%) [3.4 months (1.4-5.5)], and part 2, 7 of 39 (18%) [1.7 months (CX) to 14.8 months (END)]. Neither a predictive biomarker for SD nor evidence of pharmacodynamic effects was identified. There was a trend to significance between a reduction in lymphocyte HLA-E total score and pharmacodynamics. CONCLUSIONS: Monalizumab 10 mg/kg i.v. every 2 week is well tolerated in patients with pretreated gynecologic cancers. Short-term disease stabilization was observed. Future studies should assess combinations with other agents, including immunotherapeutics.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Agents, Immunological/administration & dosage , Endometrial Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Uterine Cervical Neoplasms/drug therapy , Abdominal Pain/chemically induced , Abdominal Pain/epidemiology , Administration, Intravenous , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Canada/epidemiology , Cohort Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Resistance, Neoplasm , Endometrial Neoplasms/pathology , Fatigue/chemically induced , Fatigue/epidemiology , Female , Humans , Middle Aged , Nausea/chemically induced , Nausea/epidemiology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Ovarian Neoplasms/pathology , Response Evaluation Criteria in Solid Tumors , Uterine Cervical Neoplasms/pathology , Vomiting/chemically induced , Vomiting/epidemiologyABSTRACT
Writing in plain language makes it easier for patients to read, understand, and make informed decisions about sperm banking. Greater attention to the issue and properly designed educational brochures for use by nurses in oncology and reproductive health is of evident importance but of unknown impact. A multidisciplinary clinical team followed an evidence-based, patient-centered approach to develop "plain language" patient education materials about sperm banking for adolescent and young adult (AYA) males with cancer. A patient education booklet was produced and implemented as part of the planned patient education for AYA male oncology patients at McMaster Children's Hospital, Hamilton Health Sciences, in Hamilton, Ontario, Canada. The patient education booklet for use by health professionals as a teaching tool to facilitate discussion with AYA males has been produced with the hope that it will contribute to better informed decision making regarding sperm banking and increased use of this technology for fertility preservation.