Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumab in subjects with microsatellite-stable metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma and other solid tumors.

Background: Pixatimod is a unique activator of the Toll-like Receptor 9 pathway. This phase I trial evaluated safety, efficacy and pharmacodynamics of pixatimod and PD-1 inhibitor nivolumab in immunologically cold cancers.

Methods: 3+3 dose escalation with microsatellite stable metastatic colorectal cancer (MSS mCRC) and metastatic pancreatic ductal adenocarcinoma (mPDAC) expansion cohorts.

Immunomodulatory activities of pixatimod: emerging nonclinical and clinical data, and its potential utility in combination with PD-1 inhibitors.

Background: Pixatimod (PG545) is a novel clinical-stage immunomodulatory agent capable of inhibiting the infiltration of tumor-associated macrophages (TAMs) yet also stimulate dendritic cells (DCs), leading to activation of natural killer (NK) cells. Preclinically, pixatimod inhibits heparanase (HPSE) which may be associated with its inhibitory effect on TAMs whereas its immunostimulatory activity on DCs is through the MyD88-dependent TLR9 pathway. Pixatimod recently completed a Phase Ia monotherapy trial in advanced cancer patients.

A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours.

Background: PG545 (pixatimod) is a novel immunomodulatory agent, which has been demonstrated to stimulate innate immune responses against tumours in preclinical cancer models.

Methods: This Phase I study investigated the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of PG545 monotherapy. Escalating doses of PG545 were administered to patients with advanced solid malignancies as a weekly 1-h intravenous infusion.

PG545 enhances anti-cancer activity of chemotherapy in ovarian models and increases surrogate biomarkers such as VEGF in preclinical and clinical plasma samples.

Background: Despite the utility of antiangiogenic drugs in ovarian cancer, efficacy remains limited due to resistance linked to alternate angiogenic pathways and metastasis. Therefore, we investigated PG545, an anti-angiogenic and anti-metastatic agent which is currently in Phase I clinical trials, using preclinical models of ovarian cancer.

Methods: PG545's anti-cancer activity was investigated in vitro and in vivo as a single agent, and in combination with paclitaxel, cisplatin or carboplatin using various ovarian cancer cell lines and tumour models.

Intentional injury reported by young people in the Federated States of Micronesia, Kingdom of Tonga and Vanuatu.

Background: Intentional injury presents a threat to the physical and psychological well being of young people, especially in developing countries, which carry the greatest part of the global injury burden. While the importance of this problem is recognized, there are limited population data in low and middle income countries that can guide public health action. The present study investigates the prevalence and distribution of intentional injury among young people in three Pacific Island societies, and examines behavioural and psychosocial factors related to risk of intentional injury.

Age-specific interval breast cancers in New South Wales and meta-analysis of studies of women aged 40-49 years.

Objective: To compare interval cancers in the 40-49 year age group with other age groups in New South Wales and with published trials and service studies.

Setting: New South Wales data were derived from the population-based biennial mammography screening program, which achieved state-wide coverage in 1995. Women aged 40-49 years screened during 1995-1998 were included.

Contemporary patterns of Pacific Island mortality.

Background: The Pacific Island countries are at different stages of the demographic and epidemiological transitions. The availability of accurate and current mortality data is of vital importance for priority setting in health. Available mortality data generally underestimate death rates among both children and adults.