NCT03983954

Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumor, Including a Cohort Expansion in Esophageal Cancer.

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
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: NeoTX Therapeutics Ltd. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed description

This Phase 1b study was originally designed for patients with tumors reported to have a high probability of expressing the 5T4 antigen. An amended protocol extended the eligibility criteria of patients recruited to the maximum tolerated dose (MTD) cohort, to include colorectal cancer (CRC) and GE carcinomas. Following the Dose Escalation part, antibodies binding to NAP have been shown to interfere with drug exposure, which makes it unlikely that patients could effectively receive more than 3 cycles of NAP. Obinutuzumab pretreatment was added to the combination of durvalumab and NAP given at the 2 highest safe dose levels of the combination of durvalumab and NAP in the dose-escalation part of this Phase 1b study (3 patients per dose level), and to the MTD expansion part that included several cohorts. The combination of NAP/durvalumab combination will be further evaluated at the Recommended Phase 2 Dose (RP2D) established in the dose- escalation part, (10 µg/kg/dose), in an expansion cohort of subjects with advanced/metastatic carcinoma of the esophagus.

Conditions

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

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Obinutuzumab, naptumomab estafenatox and durvalumab	Obinutuzumab is given intravenous (I.V.) 1,000 mg concentrate for solution for infusion, as pre-treatment. Dose escalation and MTD Expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses. Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days. Esophageal cohort expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses on cycles 1-6 and one dose per cycle starting cycle 7. Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle during cycles 1-6, and at a dose of 1500 mg delivered once every 28 days starting cycle 7.
COMBINATION_PRODUCT	Naptumomab estafenatox and durvalumab	NAP was given as an intravenous (I.V.) bolus injection at multiple doses. Durvalumab was given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.

Timeline

• Start date: 2019-10-10
• Primary completion: 2027-03-01
• Completion: 2027-03-01
• First posted: 2019-06-12
• Last updated: 2025-11-28

Locations

9 sites across 2 countries: India, Israel

Regulatory

• FDA-regulated drug study