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

Prostate Cancer Clinical Trial

Official title: Phase 1B, Open-Label, Dose Escalation and Cohort Expansions Trial of Naptumomab Estafenatox (NAP, ABR-217620) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced or Metastatic Solid Tumors

Status Active, not recruiting

Clinical Trial Summary

This is a dose escalation, MTD expansion (Phase 1b) and cohort expansions (Phase 2) study to assess the safety and tolerability of a combination of NAP with durvalumab in subjects with selected advanced or metastatic solid tumors.

Clinical Trial Description

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

Patients in the dose-escalation part are 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 are assessed with obinutuzumab given prior to the initiation of that regimen.

MTD expansion part, in which approximately 10-15 patients are treated at the confirmed MTD of NAP. Ten additional patients are enrolled at the previous dose level to assess whether a lower dose may achieves a better risk-benefit balance. This cohort recruits 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 is required. This expansion cohort will help assess the biologic activity of the combination and to gain some preliminary insights on its potential antitumor activity.

Additional group of approximately 10 patients ("Obi (-7)" group) will be enrolled to test an abbreviated regimen of obinutuzumab pre-treatment. A single infusion of 1000 mg obinutuzumab will be administered on day (-7) prior to initiation of Cycle 1 of the combination of NAP and durvalumab. NAP and durvalumab will be given in the same dose and regimen as in this MTD expansion cohort.

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. ;

Related Conditions & MeSH terms

• Bladder Cancer
• Breast Neoplasms
• Carcinoma
• Carcinoma, Squamous Cell
• Cervical Squamous Cell Carcinoma
• Colorectal Cancer Metastatic
• Endometrial Cancer
• Endometrial Neoplasms
• ER+ Breast Cancer
• GastroEsophageal Cancer
• Head and Neck Squamous Cell Carcinoma
• Hepatocellular Carcinoma
• HER2-negative Breast Cancer
• Melanoma
• Mesothelioma
• NSCL2 Gene Mutation
• NSCLC
• Ovarian Cancer
• Pancreatic Adenocarcinoma
• Prostate Cancer
• Renal Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urothelial Cancer

• NCT number: NCT03983954
• Study type: Interventional
• Source: NeoTX Therapeutics Ltd.
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 10, 2019
• Completion date: October 1, 2026