ARTISTRY-7: phase III trial of nemvaleukin alfa plus pembrolizumab vs chemotherapy for platinum-resistant ovarian cancer.

Standard single-agent nonplatinum chemotherapy provides only modest benefit in a small proportion of patients with platinum-resistant/-refractory ovarian cancer, with objective response rates of 6-20% and progression-free survival of ≈3-4 months. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel cytokine designed to capture and expand the therapeutic potential of high-dose interleukin-2 (IL-2) while mitigating its associated toxicity issues. Nemvaleukin preferentially activates cytotoxic CD8+ T cells and natural killer cells with minimal, non-dose-dependent effects on CD4+ regulatory T cells. The global, randomized, open-label, phase III ARTISTRY-7 trial will compare efficacy and safety of nemvaleukin plus pembrolizumab with chemotherapy in patients with platinum-resistant ovarian cancer. The primary end point is investigator-assessed progression-free survival. Clinical Trial Registration: GOG-3063; ENGOT-OV68; NCT05092360 (ClinicalTrials.gov).

In many patients with ovarian cancer who are treated with platinum-based chemotherapy, the tumor comes back after a few months and fails to respond to repeated treatment. This type of disease is called platinum-resistant ovarian cancer (PROC). Researchers are searching for new medicines to help more patients with PROC. One treatment approach that has shown promise in different cancers is called immunotherapy. These medicines work by helping the body's immune system attack cancer cells. One of the immunotherapies being studied is called nemvaleukin. It is designed to trigger specific immune responses that may result in the immune system attacking cancer cells while potentially avoiding other immune responses that can block the attack or cause certain unwanted side effects. Nemvaleukin is being studied in a variety of cancer types. In a worldwide clinical trial called ARTISTRY-7, researchers are investigating how nemvaleukin works in patients with PROC when given with another immunotherapy called pembrolizumab. Patients who participate in this trial will be randomly assigned to one of four treatment groups: the combination of nemvaleukin and pembrolizumab, nemvaleukin by itself, pembrolizumab by itself, or a type of chemotherapy selected by the treating physician. The main purpose of ARTISTRY-7 is to understand whether the combination of nemvaleukin and pembrolizumab helps patients with PROC live longer without their cancer getting worse. At the time of this writing, ARTISTRY-7 is open for new patients to join.

Phase I dose escalation study of dual PI3K/mTOR inhibition by Sapanisertib and Serabelisib in combination with paclitaxel in patients with advanced solid tumors.

BACKGROUND: Phase I trial to determine the safety and efficacy of paclitaxel, sapanisertib, and serabelisib. PATIENTS AND METHODS: Patients with previously treated advanced solid tumors were eligible for this open label, cohort study of sapanisertib (TAK-228) and serabelisib (TAK-117) with weekly paclitaxel. A traditional 3 + 3 dose escalation design with 5 dosing cohorts was used. Patient reported outcomes were also evaluated. RESULTS: 19 heavily pretreated patients were enrolled (10 ovarian, 3 breast, and 6 endometrial cancers). All patients received comprehensive genomic profiling prior to enrollment. RP2D is sapanisertib 3 or 4 mg, serabelisib 200 mg on days 2-4, 9-11, 16-18 and 23-25 with paclitaxel 80 mg/m2 on days 1, 8 and 15 every 28 days. All patients in Cohort 5 required dose reductions and one patient experienced a DLT. The most frequent grade 3 or 4 adverse events were decreased WBCs (20%), nonfebrile neutropenia (12%), anemia (9%), elevated liver enzymes (4%), and hyperglycemia (11%). 3 patients had a CR, 4 had a PR, and 4 patients had SD > six months. ORR was 47% and CBR was 73% in 15 evaluable patients. Including all 19 enrolled patients, the PFS was 11 months and OS is still ongoing at 17 months. CONCLUSIONS: The combination of sapanisertib, serabelisib, and paclitaxel was safe and generally well tolerated. Preliminary efficacy was remarkable in an area of unmet need, especially for patient with PI3K/AKT/mTOR pathway aberrations. Positive effects and sustained clinical benefit were even seen in patients that were refractory to platinum and had failed taxane, everolimus, or temsirolimus. CLINICAL TRIAL NUMBER: ClinicalTrials.gov, NCT03154294.

Single-port risk-reducing salpingo-oophorectomy with and without hysterectomy: surgical outcomes and learning curve analysis.

OBJECTIVE: Based on considerable prospective data, risk-reducing salpingo-oophorectomy (RRSO) is one of the most beneficial interventions available to reduce ovarian/breast cancer risk in BRCA carriers and high-risk women. The purpose of this study was to describe the initial surgical outcomes and learning curve analysis associated with laparoendoscopic single-site (LESS) RRSO with and without hysterectomy. METHODS: A retrospective, multi-institutional analysis of BRCA carriers and women at high risk for breast/ovarian cancer who underwent LESS RRSO with and without hysterectomy in 2009 was performed. Data collected included age, BMI, procedure, operative time, length of hospital stay, postoperative pain scores, and post operative complications. Student t-test, Pearson correlation coefficient, and multivariate linear regression were used for analysis. RESULTS: A total of 58 patients were evaluated; 36 (63%) were BRCA1/2 carriers and 38 (63%) had breast cancer. Patients' mean age and BMI were 46 years and 27 kg/m(2), respectively. Most patients were Caucasian (76%), and at the time of prophylactic surgery, 53% of patients were undergoing active breast cancer treatment. Mean operative time was 38.1 minutes (16-80 minutes). All cases were performed successfully via the LESS approach, and there were no surgical complications. Multivariate linear regression analysis was done, and after controlling for study site, previous abdominal surgery, active cancer treatment, and BMI, operative time was only influence by number of cases performed, p=0.019. CONCLUSIONS: LESS RRSO is feasible and safe with favorable surgical and cosmetic outcomes. In our experience, surgical proficiency is possible after 10-15 cases. The LESS approach may be ideal for BRCA mutation carriers and breast cancer patients because of a short convalescence, permitting minimal interruption in any ongoing cancer treatment and the potential psychological benefits from improved cosmesis and pain control. Prospective studies are needed to assess the relative benefits of LESS compared with more conventional minimally invasive approaches.