Yuka Kasamatsu

A phase II, open-labeled, single-arm study of dose-dense paclitaxel plus carboplatin in advanced or recurrent uterine endometrial cancer treatment: a KCOG-G1303, DOENCA trial

To determine the safety and efficacy of dose-dense (dd) paclitaxel (PTX) and carboplatin (CBDCA) in treating advanced or recurrent endometrial cancer. Women aged 20-75 years with histologically confirmed endometrial cancer, the International Federation of Gynecology and Obstetrics (FIGO) stage III disease with some residual tumor, FIGO stage IV disease, recurrence after front-line curative treatment, or recurrence after second-line chemotherapy or radiotherapy were enrolled in this study. PTX (80 mg/m²) was administered intravenously (IV) to every participant on days 1, 8, and 15, and CBDCA (area under the curve of 5) was administered IV on day 1 once every 3 weeks until the disease progressed, unacceptable adverse events occurred, or consent was withdrawn. The primary endpoint was the response rate (RR), while the secondary endpoints were progression-free survival, overall survival, and adverse effects. Forty-eight participants were enrolled, and 46 were eligible to receive treatment. The patients' median age was 61 years (range, 43-76 years). Twenty-two participants had experienced recurrence, and the remaining patients had primary advanced endometrial cancer. There were 10 cases of serous carcinoma, 3 cases of endometrioid carcinoma G3, 2 cases of carcinosarcoma, and 2 cases of clear-cell carcinoma according to histology. Twenty-nine participants (63.0%) received ≥6 cycles of chemotherapy. The RR (complete, 13 cases; partial, 20 cases) was 71.3% (95% confidence interval: 59.0%-84.5%). The dd PTX with CBDCA is feasible and available as a treatment option for advanced or recurrent endometrial cancer. UMIN Clinical Trials Registry Identifier: UMIN000017138.

Phase I Trial of First-line Bintrafusp Alfa in Patients with Locally Advanced or Persistent/Recurrent/Metastatic Cervical Cancer

Abstract Purpose: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFβ receptor II (a TGFβ “trap”) fused to a human IgG1 mAb blocking programmed death-ligand 1 (PD-L1), was evaluated as treatment in patients with locally advanced or persistent, recurrent, or metastatic (P/R/M) cervical cancer. Patients and Methods: In this multicenter, open-label, phase Ib trial (NCT04551950), patients with P/R/M cervical cancer received bintrafusp alfa 2,400 mg once every 3 weeks plus cisplatin or carboplatin plus paclitaxel with (Cohort 1A; n = 8) or without (Cohort 1B; n = 9) bevacizumab; patients with locally advanced cervical cancer received bintrafusp alfa 2,400 mg every 3 weeks plus cisplatin plus radiation, followed by bintrafusp alfa monotherapy maintenance (Cohort 2; n = 8). The primary endpoint was safety; secondary endpoints included efficacy (including objective response rate) and pharmacokinetics. Results: At the data cutoff of April 27, 2022, patients in Cohorts 1A, 1B, and 2 had received bintrafusp alfa for a median duration of 37.9, 31.1, and 16.7 weeks, respectively. Two dose-limiting toxicities (grade 4 amylase elevation and grade 3 menorrhagia) unrelated to bintrafusp alfa were observed in Cohort 1B and none in other cohorts. Most treatment-emergent adverse events of special interest were grades 1–2 in severity, most commonly anemia (62.5%–77.8%) and bleeding events (62.5%–77.8%). Objective response rate was 75.0% [95% confidence interval (CI), 34.9–96.8], 44.4% (95% CI, 13.7–78.8), and 62.5% (95% CI, 24.5–91.5) in Cohorts 1A, 1B, and 2, respectively. Conclusions: Bintrafusp alfa had manageable safety and demonstrated clinical activity, further supporting the investigation of TGFβ/PD-L1 inhibition in human papillomavirus–associated cancers, including cervical cancer.