Phase Ib/IIa Trial to Evaluate Oregovomab and Nivolumab in Epithelial Cancer of Ovarian, Tubal or Peritoneal Origin — ORION-01  

Epithelial Ovarian Cancer Clinical Trial

Official title: A Phase Ib/IIa Clinical Trial to Evaluate the Safety and Activity of Oregovomab and Nivolumab as a Combinatorial Immunotherapy Strategy in Patients With Recurrent Epithelial Cancer of Ovarian, Tubal or Peritoneal Origin

Status Terminated

Clinical Trial Summary

The purpose of this study is to characterize the safety and tolerability, identify a recommended dose for expansion (RDE) / recommended phase II dose (RP2D), pharmacodynamics, and antitumor activity of Oregovomab vaccination in combination with Nivolumab as a novel combinatorial immunotherapeutic strategy in in female patients with recurrent epithelial ovarian cancer (EOC) who progressed after two or more prior lines of cytotoxic chemotherapy.

Clinical Trial Description

This study tests the hypothesis that the combination of Oregovomab and Nivolumab will improve intracellular Cancer Antigen (CA) 125 antigen processing and elicit a stronger systemic CA 125-specific T cell response; in a manner that is synergistic, safe, and clinically efficacious in patients with relapsed EOC.

This is an open-label, single-arm, phase Ib/IIa, single-center study with dose finding and dose expansion parts.

In the phase Ib part, clinically recommended doses as monotherapy for Oregovomab (IV 2 mg Q4W, dose level 1) and Nivolumab (IV 240 mg Q2W) will be the starting doses for their combined use.

A modified "3+3" dose finding design will be employed, with 2 lower dosages of Oregovomab (dose level -1 at 1 mg Q4W; level -2 at 0.5 mg Q4W) specified in case of excessive toxicity (defined as ≥ 2 dose limiting toxicities (DLTs) out of first 3 patients, or all 6 patients) encountered at dose level 1. Three patients will be initially enrolled into dose level 1. If 0 or 1 DLT is observed, another 3 patients will be enrolled into the same dose level; otherwise de-escalate and enroll 3 patients at dose level -1. If ≤ 1 DLT is observed among the 6 patients, dose level 1 will be the RDE/RP2D of Oregovomab to be combined with Nivolumab. Likewise, in the event of de-escalation, if 0 or 1 DLT is observed at a lower dose level, a further 3 patients will be enrolled for that level; if ≤ 1 DLT is observed out of the 6 patients, that dose level will be the RDE/RP2D.

A minimum of 6 and a maximum of 18 patients will be enrolled in the dose finding part.

Approximately 14 patients are to enroll in the dose expansion part wherein they will receive Oregovomab at RDE/RP2D, combined with Nivolumab. In total, 20 patients from the dose finding and dose expansion cohorts will be treated at RDE/RP2D, and be included in the phase IIa study population.

Patients will be followed up for survival and post-progression treatment(s) over a duration of up to 36 months from the time of treatment initiation (i.e., Week 0 until up to 36 months). ;

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Epithelial Ovarian Cancer

• NCT number: NCT03100006
• Study type: Interventional
• Source: National Cancer Centre, Singapore
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 22, 2017
• Completion date: April 17, 2020