Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumors

Summary

Participation Requirements

Description

This Phase 1b, open-label, multicenter (n=3-5), prospective, dose-finding and MTD cohort expansion study, will accrue patients with previously treated solid tumors known with high likelihood of 5T4 antigen expression on tumor cells. Patients in the dose-escalation part will be treated with the combi...

This Phase 1b, open-label, multicenter (n=3-5), prospective, dose-finding and MTD cohort expansion study, will accrue patients with previously treated solid tumors known with high likelihood of 5T4 antigen expression on tumor cells. Patients in the dose-escalation part will be treated with the combination of NAP and durvalumab using a fixed dose of durvalumab and the 3+3 design for NAP dose escalations. The (Maximum Tolerated Dose (MTD) of NAP for the combination treatment will be established based on Dose Limiting Toxicities (DLTs) occurring during the first cycle of the treatment. A second dose escalation part is performed at the second highest safe dose in the dose escalation phase, pre-treated with obinutuzumab (anti-CD20), for elimination of anti-drug antibodies (ADAs) to NAP. In this part, the safety of the NAP-durvalumab combination will be assessed with obinutuzumab given prior to the initiation of that regimen. If safety and successful elimination of ADAs is confirmed, pretreatment with obinutuzumab will be tested further in the MTD expansion cohort. MTD expansion part, in which 10-15 patients will be treated at the confirmed MTD of NAP. This cohort will accrue patients with the same tumor types as in the escalation part, as well as 5T4-positive colorectal cancer (CRC) and gastro-esophageal cancer (GE). Measurable disease, available tumor deposit and repeat biopsy are required. This expansion cohort will help assess the biologic activity of the combination and to gain some preliminary insights on its potential antitumor activity. The following solid tumors known to have > 80% probability of 5T4 expression and thus may be included in both the dose escalation phase and the MTD expansion: breast cancer, epithelial ovarian cancer, cervical and endometrial cancer, pancreatic cancer, renal and urothelial cancer, head and neck, mesothelioma, melanoma, hepatic carcinoma, prostate cancer, and Non-Small Cell Lung Cancer (NSCLC). Prior PD-1 or PD-L1 therapy is acceptable.

Tracking Information