NCT04503278

A Clinical Study of the Safety and Effectiveness of an Investigational Cell Therapy Given With and Without an Investigational RNA-based Vaccine in Patients With Organ Tumors

Phase I/IIa, First-in-human, Open-label, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of CLDN6 CAR-T With or Without CLDN6 RNA-LPX in Patients With CLDN6-positive Relapsed or Refractory Advanced Solid Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 214 (estimated)
• Sponsor: BioNTech Cell & Gene Therapies GmbH · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase I, FIH, open-label, multi-site, dose escalation trial with expansion cohorts to evaluate safety and preliminary efficacy of claudin 6 (CLDN6) chimeric antigen receptor T cells (CAR-T) with or without CLDN6 ribonucleic acid lipoplexes (RNA-LPX) in patients with CLDN6-positive relapsed or refractory advanced solid tumors.

Detailed description

CLDN6 CAR-T is used as a general term to refer to CLDN6 CAR-T cells from the manual and automated manufacturing processes. The trial consists of two parts. The trial began using a manual CLDN6 CAR-T production process. Part 1 is a CLDN6 CAR-T dose escalation in lymphodepleted patients until the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of CLDN6 CAR-T are defined. Dose escalation with CLDN6 CAR-T cells from the automated manufacturing process follows an accelerated titration design, as opposed to the classical 3+3 trial design used for the dose escalation with CLDN6 CAR-T manufactured with the manual process. In addition, an optional de-escalation dose level may be explored to further evaluate clinical safety and efficacy of CLDN6 CAR-T manufactured with the automated process. Part 2 is a vaccine-modulated dose escalation using a bifurcated design until the MTD and/or RP2D of CLDN6 CAR-T + CLDN6 RNA-LPX are defined. The trial started with a CLDN6 encoding uridine containing RNA formulated in lipoplexes (CLDN6 uRNA-LPX). In order to optimize CAR-T cell persistence in patients, an alternative RNA-LPX, CLDN6 modRNA-LPX, will be tested once the RP2D dose for CLDN6 CAR-T ± CLDN6 RNA-LPX is identified. The planned trial duration per patient in the main trial is 25 months. Patients exposed to genetically engineered therapies may be at risk of delayed adverse events. Therefore, after patients complete or prematurely discontinue participation in the main trial, they will be asked to participate in a long-term follow-up (LTFU) period to assess long-term safety and efficacy for up to 15 years. Patients will be asked to re-consent to participate in this LTFU period.

Conditions

• Solid Tumor

Interventions

Type	Name	Description
BIOLOGICAL	CLDN6 CAR-T	administered as an intravenous (i.v.) infusion.
BIOLOGICAL	CLDN6 uRNA-LPX/CLDN6 modRNA-LPX	administered as an i.v. injection at protocol-specified intervals.

Timeline

• Start date: 2020-09-16
• Primary completion: 2028-08-01
• Completion: 2041-08-01
• First posted: 2020-08-07
• Last updated: 2026-04-17

Locations

12 sites across 4 countries: Australia, Germany, Netherlands, Sweden