maytansine and Fallopian-Tube-Neoplasms

To evaluate the safety profile and preliminary antitumor activity of mirvetuximab soravtansine when administered in combination with carboplatin to relapsed ovarian cancer patients.. Patients with recurrent, platinum-sensitive epithelial ovarian or fallopian tube cancer were enrolled. Eligibility included a minimum requirement of tumor FRα positivity (≥25% of cells with ≥2+ staining intensity). Patients received escalating doses of mirvetuximab soravtansine and carboplatin on day 1 of a 21-day cycle (once every 3 weeks). Mirvetuximab soravtansine maintenance therapy was permitted, at the investigators discretion, following cessation of carboplatin treatment. Adverse events, tumor response, and progression-free survival (PFS) were determined.. Eighteen patients were enrolled and dosed with combination therapy; thirteen continued with mirvetuximab soravtansine maintenance following carboplatin discontinuation. Mirvetuximab soravtansine dosing was escalated from 5 to 6 mg/kg (adjusted ideal body weight) and carboplatin from AUC4 to AUC5. Adverse events were generally mild (≤ grade 2) with nausea, diarrhea, thrombocytopenia, blurred vision, and fatigue being the most common treatment-emergent toxicities. For all evaluable patients (n = 17), the confirmed objective response rate (ORR) was 71%, including three complete responses and nine partial responses, and the median PFS was 15 months. A median duration of response was not reached.. These data demonstrate that mirvetuximab soravtansine combined with carboplatin is a well-tolerated and highly active regimen in recurrent, platinum-sensitive ovarian cancer. Further evaluation of this combination in a randomized fashion is warranted.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cohort Studies; Diarrhea; Disease-Free Survival; Drug Resistance, Neoplasm; Fallopian Tube Neoplasms; Fatigue; Female; Folate Receptor 1; Humans; Immunoconjugates; Incidence; Maximum Tolerated Dose; Maytansine; Middle Aged; Nausea; Neoplasm Recurrence, Local; Ovarian Neoplasms; Thrombocytopenia; Treatment Outcome

Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined. Results Forty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%) being the most commonly observed treatment-related toxicities. Grade 3 fatigue and hypotension were reported in two patients each (4%). For all evaluable patients, the confirmed objective response rate was 26%, including one complete and 11 partial responses, and the median PFS was 4.8 months. The median duration of response was 19.1 weeks. Notably, in the subset of patients who had received three or fewer prior lines of therapy (n = 23), an objective response rate of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed. Conclusion IMGN853 exhibited a manageable safety profile and was active in platinum-resistant ovarian cancer, with the strongest signals of efficacy observed in less heavily pretreated individuals. On the basis of these findings, the dose, schedule, and target population were identified for a phase III trial of IMGN853 monotherapy in patients with platinum-resistant disease.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Diarrhea; Disease-Free Survival; Drug Resistance, Neoplasm; Fallopian Tube Neoplasms; Fatigue; Female; Folate Receptor 1; Humans; Hypotension; Immunoconjugates; Maytansine; Middle Aged; Nausea; Ovarian Neoplasms; Peritoneal Neoplasms; Platinum Compounds; Response Evaluation Criteria in Solid Tumors; Retreatment; Vision Disorders