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Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class antibody–drug conjugate targeting folate receptor α (FRα), approved by the US Food and Drug Administration for the treatment of platinum-resistant ovarian cancer in the USA. Here, we report patient-reported outcomes for participants treated with MIRV compared with investigator's choice of chemotherapy from the phase 3 MIRASOL trial, which met its primary endpoint of progression-free survival and key secondary endpoints of objective response rate and overall survival. The MIRASOL trial was a confirmatory, phase 3, randomised, controlled, open-label trial, building on the phase 2 SORAYA trial which had previously demonstrated the safety and efficacy of MIRV in platinum-resistant ovarian cancer. Patients 18 years or older with a confirmed platinum-resistant, recurrent high-grade serous epithelial ovarian cancer diagnosis were recruited from 253 sites including hospitals, academic centres, and community centres in 21 countries. Patients must have received one to three previous systemic anticancer therapies, and have high FRα tumour expression (≥75% tumour cells with an immunohistochemistry score of ≥2+ membrane staining using the PS2+ scoring method), one or more lesions with measurable disease, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to MIRV or investigator's choice of chemotherapy, stratified by number of previous therapy lines and the type of investigator's choice of chemotherapy. Therapies were administered in an open-label manner; MIRV was administered intravenously at 6 mg/kg of adjusted ideal bodyweight every 3 weeks. The primary endpoint was progression-free survival. Key secondary endpoints were objective response rate, overall survival, and a 15·0-point or greater improvement at week 8 or 9 in abdominal and gastrointestinal symptoms using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module (EORTC QLQ-OV28) in the intention-to-treat population. The MIRASOL trial was registered at ClinicalTrials.gov (NCT04209855), the Gynecologic Oncology Group (GOG 3045), and the European Network of Gynaecological Oncological Trial Groups (ENGOT-ov55), and is complete. Between Feb 3, 2020, and Aug 3, 2022, 453 patients were enrolled and randomly assigned to treatment (227 to the MIRV group and 226 to the investigator's choice of chemotherapy group). All patients were female; 301 (66%) participants were White, 53 (12%) were Asian, 13 (3%) were Black, and 86 (19%) were of another race or not reported; 27 (6%) were Hispanic or Latino. The median follow-up for the study, determined by the reverse Kaplan–Meier method, was 13·1 months (95% CI 12·1–14). QLQ-OV28 completion rates were 86% (365 of 425) at baseline and 81% (282 of 349) at week 8 or 9. 34 (21·0%; 95% CI 15·0–28·1) of 162 patients treated with MIRV reported improvement in QLQ-OV28 abdominal and gastrointestinal scores, compared with 23 (15·3%; 10·0–22·1) of 150 patients treated with the investigator's choice of chemotherapy. These differences were not statistically significant (odds ratio 1·5 [95% CI 0·8–2·6]; p=0·26). MIRV did not seem to impair or improve patient quality of life compared with investigator's choice of chemotherapy. The similar quality-of-life outcomes in the two treatment groups, combined with the previously reported higher efficacy of MIRV compared with single-agent chemotherapy, support MIRV as new treatment option for FRα-positive platinum-resistant ovarian cancer. AbbVie.

The dose-dense delivery of chemotherapy (greater frequency of drug delivery) was explored in women with advanced ovarian cancer. All patients received carboplatin; half received paclitaxel weekly and half every 3 weeks. There were no between-group differences in progression-free survival. Ovarian cancer, the most lethal gynecologic cancer, is responsible for approximately 14,000 deaths in the United States annually. 1 The incorporation of bevacizumab, a monoclonal antibody against vascular endothelial growth factor, in the treatment regimen prolongs progression-free survival but not overall survival. 2 – 5 A dose-dense regimen of paclitaxel involving greater frequency of drug delivery may enhance its antineoplastic effect by eliciting antiangiogenic and proapoptotic properties. 6 – 9 Weekly paclitaxel therapy prolonged survival among patients with early-stage breast cancer and those with metastatic breast cancer. 10 , 11 In a study involving patients with ovarian cancer, Japanese investigators found that dose-dense weekly paclitaxel prolonged progression-free . . .

Resistance to platinum-based therapy poses a significant clinical challenge for the management of advanced ovarian cancer, a leading cause of cancer mortality among women. Mirvetuximab soravtansine is a novel antibody-drug conjugate that targets folate receptor-α, a validated molecular target for therapeutic intervention in this disease. Here, we examine mirvetuximab soravtansine's mechanism of action and pharmacology, and review its clinical evaluation in ovarian cancer to date. We focus on the favorable tolerability and encouraging signals of efficacy that have emerged, most notably in patients with platinum-resistant disease. Ongoing Phase III monotherapy and Phase Ib/II combination trials evaluating its activity in the setting of platinum resistance are emphasized, which will help define its role in the evolving landscape of ovarian cancer therapy.

This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-γ. Three dose limiting toxicities are reported at the highest dose cohorts. We report only one patient with any immune related adverse event (irAE). No irAEs ≥ grade 3 are observed and no patients require corticosteroids. The maximum tolerated dose of IFN-γ is 75 mcg/m 2 , however based on a composite of safety, clinical, and correlative factors the RP2D is 50 mcg/m 2 . Exploratory analyses of efficacy in the phase I cohorts demonstrate one patient with a complete response, and five have achieved stable disease. Pre-planned correlative assessments of circulating immune cells demonstrate intermediate monocytes with increased PD-L1 expression correlating with IFN-γ dose and treatment duration. Interestingly, post-hoc analysis shows that IFN-γ induction increases circulating chemokines and is associated with an observed paucity of irAEs, warranting further evaluation. ClinicalTrials.gov Trial Registration: NCT02614456. The majority of cancer patients do not respond to single agent immune checkpoint blockade and several combinatorial approaches have now been tested. Here the authors report the results of a phase I dose escalation trial of nivolumab (anti-PD1) in combination with IFN-γ in patients with advanced solid tumors.

Objectives. The benefit of adjuvant chemotherapy in patients with localized uterine leiomyosarcoma (LMS) remains unclear due to a lack of randomized studies and data only from small retrospective series to rely on. We sought to identify factors associated with the administration of chemotherapy and to determine the trends in the usage of adjuvant chemotherapy in patients with nonmetastatic uterine LMS. Methods. Patients diagnosed with nonmetastatic uterine LMS between 2004 and 2014 were identified from the National Cancer Database (NCDB). Multiple regression was used to determine factors with a significant impact on patient receipt of chemotherapy. Kaplan–Meier curves and the Cox model were used to determine the effect of adjuvant chemotherapy on overall survival (OS). Results. 2,732 uterine LMS patients were identified. Patients older than 65 were less likely to receive chemotherapy than their younger counterparts. Patients with stage I or stage II cancer were less likely to receive chemotherapy, whereas individuals with positive regional lymph nodes and those who had received radiation were more likely. In this cohort, adjuvant chemotherapy had no significant impact on OS (HR, 1.04; 95% CI, 0.90–1.22; P=0.5768). However, administration of chemotherapy significantly increased from 2004 to 2014 (P<0.0001). Conclusions. Expected tumor characteristics such as higher stage of tumor were associated with receipt of chemotherapy. Although adjuvant chemotherapy demonstrated no benefit over observation on OS in patients with nonmetastatic LMS, the number of patients being treated with chemotherapy continued to increase from 2004 to 2014.

Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States. We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes. A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%). Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).

Background Most cases of ovarian cancer are epithelial in origin and diagnosed at advanced stage when the cancer is widely disseminated in the peritoneal cavity. The objective of this study was to establish an immunocompetent syngeneic mouse model of disseminated epithelial ovarian cancer (EOC) to facilitate laboratory-based studies of ovarian tumor biology and preclinical therapeutic strategies. Methods Individual lines of Tg MISIIR-TAg transgenic mice were phenotypically characterized and backcrossed to inbred C57BL/6 mice. In addition to a previously described line of EOC-prone mice, two lines (Tg MISIIR-TAg-Low ) were isolated that express the oncogenic transgene, but have little or no susceptibility to tumor development. Independent murine ovarian carcinoma (MOVCAR) cell lines were established from the ascites of tumor-bearing C57BL/6 Tg MISIIR-TAg transgenic mice, characterized and tested for engraftment in the following recipient mice: 1) severe immunocompromised immunodeficient (SCID), 2) wild type C57BL/6, 3) oophorectomized tumor-prone C57BL/6 Tg MISIIR-TAg transgenic and 4) non-tumor prone C57BL/6 Tg MISIIR-TAg-Low transgenic. Lastly, MOVCAR cells transduced with a luciferase reporter were implanted in Tg MISIIR-TAg-Low mice and in vivo tumor growth monitored by non-invasive optical imaging. Results Engraftment of MOVCAR cells by i.p. injection resulted in the development of disseminated peritoneal carcinomatosis in SCID, but not wild type C57BL/6 mice. Oophorectomized tumor-prone Tg MISIIR-TAg mice developed peritoneal carcinomas with high frequency, rendering them unsuitable as allograft recipients. Orthotopic or pseudo-orthotopic implantation of MOVCAR cells in Tg MISIIR-TAg-Low mice resulted in the development of disseminated peritoneal tumors, frequently accompanied by the production of malignant ascites. Tumors arising in the engrafted mice bore histopathological resemblance to human high-grade serous EOC and exhibited a similar pattern of peritoneal disease spread. Conclusions A syngeneic mouse model of human EOC was created by pseudo-orthotopic and orthotopic implantation of MOVCAR cells in a susceptible inbred transgenic host. This immunocompetent syngeneic mouse model presents a flexible system that can be used to study the consequences of altered gene expression (e.g., by ectopic expression or RNA interference strategies) in an established MOVCAR tumor cell line within the ovarian tumor microenvironment and for the development and analysis of preclinical therapeutic agents including EOC vaccines and immunotherapeutic agents.

This open-label, two-arm, phase II clinical trial evaluated the antitumor activity and safety profile of PM00104 (Zalypsis ® ) administered as a 1-h, weekly, intravenous infusion (days 1, 8 and 15; every 4 weeks) at a dose of 2 mg/m 2 to patients with advanced and/or metastatic endometrial (EC) or cervical cancer (CC) after one previous line of systemic chemotherapy. Twelve patients (median age, 61.5 years) with pretreated EC received a median of 2 treatment cycles (range 1–5) and seven patients (median age, 38 years) with pretreated CC received 2 treatment cycles. None achieved objective tumor response. Median progression-free survival (PFS) was 1.8 months, and median overall survival (OS) was 5.5 months in EC (median follow-up = 20.1 months); median PFS was 1.5 months, and median OS was 5.6 months in CC (median follow-up = 17.1 months). The most common toxicities reported were mild to moderate asthenia, nausea, vomiting and diarrhea. Despite PM00104 showing mostly mild, predictable, manageable and reversible toxicity, protocol criteria for further recruitment were not met in EC, a futility analysis was done and recruitment was stopped; a low patient recruitment rate together with no evidence of activity in CC resulted in early study closure.

[...]line options for recurrent or metastatic cervical cancers result in a median PFS of around 2 to 4 months and an objective response rate of 0% to 14%.\" [...]the limited number of patients in the two groups precludes any significant comparison.\" Because all tested tumors were HPV positive, researchers could not compare these data with HPV-negative tumors, Hollebecque added. Data on duration of response in this study are limited. Because the study completed accrual in early 2016, there are a few patients out at 36 weeks on the swimmer plot.