Background Follitropin delta, a novel recombinant follicle-stimulating hormone (rFSH) preparation derived from a human cell line, has different pharmacokinetic and pharmacodynamic properties compared with existing rFSH preparations expressed by Chinese hamster ovary cells (CHO). Objectives The objective of this study was to assess the pharmacokinetic characteristics, dose proportionality, and safety of follitropin delta in healthy Chinese women. Methods This was a phase I, randomized, open-label study. Twenty-four healthy Chinese women were randomized (1:1:1) to receive a single subcutaneous administration of follitropin delta 12, 18, or 24 μg. The pharmacokinetic parameters (maximum observed serum concentration [C max ], time to reach C max [t max ], area under the serum concentration-time curve from dosing to infinity [AUC ∞ ], and elimination phase half-life [t ½ ]) of follitropin delta were derived using noncompartmental analysis. Results Following a single subcutaneous administration of follitropin delta 12, 18, or 24 μg, mean C max (0.388, 0.677, and 0.825 ng/mL, respectively) and AUC ∞ (41.3, 62.9, and 83.1 h•ng/mL, respectively) increased in a dose-proportional manner. The median t max was 24 h, and the mean t ½ was in the range of 50.5-60.9 h. All treatment-related adverse events were categorized as mild, except for one case of urticaria from the follitropin delta 18-μg dose group which was considered moderate. Only one woman presented with elevation of alanine transaminase and aspartate aminotransferase at the followup visit, which was reported as a treatment-emergent adverse event. There were no injection-site reactions and none of the participants showed any confirmed presence of treatment-induced anti-FSH antibodies. Conclusions The administration of single doses of follitropin delta to healthy Chinese women demonstrated dose-proportional pharmacokinetics over the dose range of 12-24 μg, and these doses were well tolerated. Clinical Trial Registration Clinicaltrials.gov registration no. NCT04150861.

BackgroundThere is no standard treatment for stage III lung cancer due to its low surgical resection rate, and improving PFS and survival of patients with III NSCLC has become an urgent challenge in clinical treatment. For EGFR mutation-positive patients, targeted therapy has the remarkable feature of high efficiency and low toxicity compared with first-line standard chemotherapy, and targeted neoadjuvant therapy needs to be further explored.MethodWe report 3 diagnosed cases of locally advanced unresectable NSCLC with EGFR-sensitive mutations who first received 1–2 cycles of preoperative chemotherapy neoadjuvant therapy and were treated with 110 mg daily of 3rd-generation EGFR-TKI aumolertinib instead because of poor efficacy or safety intolerance.ResultAfter 2 cycles of aumolertinib treatment, all 3 patients achieved symptomatic remission and significant tumor size reduction and achieved downstaging to allow surgical treatment. No additional operative difficulties were added during the surgery. They continued to receive adjuvant therapy with the original dose of aumolertinib after surgical treatment, and no evidence of tumor recurrence was found until the most recent imaging examination. In addition, the course of neoadjuvant and adjuvant therapy was free of serious adverse effects.ConclusionPerioperative treatment of these three cases of locally advanced unresectable NSCLC with EGFR-sensitive mutations with the third-generation EGFR-TKI aumolertinib showed significant efficacy and excellent safety and may be a new option for targeted therapy in the perioperative period.

No abstract