A phase I open-label dose-escalation study was conducted to define the safety, tolerability, and pharmacokinetics (PK) of PankoMab-GEX, a glyco-optimised humanised IgG1, with high affinity to a novel tumour-specific glycopeptide epitope of MUC1 (TA-MUC1) with excellent preclinical anti-tumour activity. Seventy-four patients with advanced TA-MUC1-positive carcinomas received PankoMab-GEX intravenously every 3 (Q3W), 2 (Q2W), or 1 (QW) week in doses of 1-2200 mg in a three-plus-three dose-escalation design until disease progression (NCT01222624). No maximum tolerated dose was reached. Adverse events were mainly mild-to-moderate infusion-related reactions (IRRs) by the first infusion in 45% of patients. Only one dose-limiting toxicity, a grade III IRR, was observed. PankoMab-GEX exhibited linear PK over all doses. Mean terminal half-life was 189 ± 66 h (Q3W), without dose dependency. A target trough level ≥50 μg/mL was reached after one infusion with doses ≥1700 mg Q3W in 80% of patients. Clinical benefit in 60 evaluable patients included one complete response in a patient with ovarian cancer treated 483 d and confirmed disease stabilisation in 19 patients lasting a median (range) of 23 (10-109) weeks. All but two of the patients with clinical benefit had received a compounded total dose ≥700 mg over a 3-week period, including 8 of 12 (67%) patients with ovarian cancer. PankoMab-GEX is safe, well tolerated, and showed promising anti-tumour activity in advanced disease. A phase IIb study is ongoing evaluating the efficacy of PankoMab-GEX as a maintenance therapy in advanced ovarian cancer.

Journal of Cancer Metastasis and Treatment is an open access journal, focusing on basic and clinical studies related to cancer cell, cell biology, oncology, radiation therapy and radiology, obstetrics and gynecology, pediatrics, surgery, hematology, neuro-oncology, etc.

Purpose: We assessed the benefit of adjuvant aspirin in patients with resected phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)–mutated colon cancer. Patients and Methods: This was a phase III, prospective, randomized, placebo-controlled, double-blind, multicenter, and multinational trial. Patients with resected colon cancer stage II and III harboring an activating PIK3CA mutation were included. Because of financial constraints, the trial was prematurely closed. Randomization was 2:1 to aspirin 100 mg versus placebo daily for 3 years. The primary endpoint was disease-free survival (DFS). Secondary endpoints included the time to disease recurrence (TTR), overall survival, and adverse events. Results: Overall, 1,040 patients were screened for PIK3CA mutations, with 112 randomized to aspirin (N = 74) and placebo (N = 38). The median age was 66 years, and 42.9% were female. After a median follow-up of 4 years, 19 DFS events occurred, including 10 in the aspirin and nine in the placebo arm. The HR for DFS was 0.57 [90% confidence interval (CI), 0.27–1.22], in favor of aspirin (P = 0.11). DFS rates at 5 years were 86.5% (90% CI, 77.7%–92.0%) in the aspirin and 72.9% (90% CI, 55.7%–84.3%) in the placebo arm. The HR for TTR was 0.49 (90% CI, 0.21–1.19, P = 0.089) in favor of aspirin. No patient experienced aspirin-related serious adverse events. Conclusions: The SAKK 41/13 is the first randomized trial to provide clinical evidence of a protective effect of adjuvant aspirin in patients with resected PIK3CA-mutant colon cancer, with clinically relevant DFS and TTR improvements. Although results were not statistically significant because of premature study closure, adjuvant aspirin warrants individual consideration in patients with resected PIK3CA-mutant colon cancer stage II and III. See related commentary by Drew et al., p. 3107