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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioNTech Cell & Gene Therapies GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Aug 2020 → ongoing

Decision date (initial)

2024-07-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514962-38-00

EudraCT number

2019-004323-20

ClinicalTrials.gov

NCT04503278

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacodynamic, Safety

To assess the safety and tolerability of claudin 6 (CLDN6) chimeric antigen receptor T cell (CAR-T) ± CLDN6 liposomally-formulated vaccine encoding ribonucleic acid (RNA-LPX) and to assess the comparability of CLDN6 CAR-T from the manual and automated processes, and to identify the maximum tolerated dose (MTD)/(recommended phase 2 dose) RP2D for each IMP (i.e., CLDN6 CAR-T ± CLDN6 RNA-LPX) based on the occurrence of dose-limiting toxicities (DLT) using the following definitions: 1) MTD is defined as the highest tolerated dose of CLDN6 CAR-T ± CLDN6 RNA-LPX where less than 33% of the patients experience a DLT, and 2) RP2D of CLDN6 CAR-T ± CLDN6 RNA-LPX based on integrated evaluation of safety and other data for all dose levels tested.

Secondary objectives 2

1. To describe the profile of soluble immune factors in CLDN6 CAR-T ± CLDN6 RNALPX
2. To evaluate anti-tumor activity of CLDN6 CAR-T ± CLDN6 RNA-LPX according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1)

Conditions and MedDRA coding

Solid Tumors

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

EMA paediatric investigation plan (PIP)

EMEA-003464-PIP01-23, EMEA-003377-PIP01-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Must have a CLDN6-positive tumor regardless of tumor histology defined as ≥50% of tumor cells expressing CLDN6 protein at an intensity of ≥2+ using a semi-quantitative immunohistochemistry (IHC) assay for specific detection of CLDN6 protein expression in formalin-fixed, paraffin-embedded neoplastic tissues.
2. Must have measurable disease per RECIST 1.1 (except for germ cell tumor where patients can be evaluated according to cancer antigen (CA)-125, AFP, or beta human chorionic gonadotropin [βhCG] [as applicable] or ovarian cancer patients where patients can be evaluated according to CA-125. The pre-treatment sample must be at least twice the upper limit of normal [ULN]).
3. Must have a histologically confirmed solid tumor that is metastatic or unresectable and for whom there is no available standard therapy likely to confer clinical benefit, or the patient is not a candidate for such available therapy.

Exclusion criteria 5

1. Has received prior CAR-T therapy, except CLDN6 CAR-T therapy.
2. Has received vaccination with live virus vaccines within 6 weeks prior to the start of lymphodepletion (LD).
3. Receives concurrent systemic (oral or i.v.) steroid therapy > 10 mg prednisolone daily, or its equivalent, for an underlying condition.
4. Current evidence of new or growing brain or spinal metastases during screening.
5. Has a history of another primary cancer within the 2 years prior to enrollment except for the following: non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, prostate cancer with currently undetectable prostate specific antigen, or other non-metastatic carcinoma that has been in complete remission without treatment for more than 2 years.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Occurrence of treatment-emergent adverse events (TEAEs) including ≥ Grade 3, serious, fatal TEAEs by relationship
2. Occurrence of dose reduction and discontinuation of investigational medicinal product (IMP) due to TEAEs
3. Occurrence of dose-limiting toxicity (DLT) during the DLT evaluation period

Secondary endpoints 4

1. Change from baseline in the levels and kinetics of soluble immune factors measured by cytokine multiplex assay
2. Objective response rate (ORR) defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per RECIST 1.1 or defined by tumor marker change from baseline when RECIST evaluation is not feasible) is observed as best overall response
3. Disease control rate (DCR) defined as the proportion of patients in whom a CR or PR or stable disease (SD) per RECIST 1.1 or defined by tumor marker change from baseline when RECIST evaluation is not feasible (SD assessed at least 6 weeks after the first dose) is observed as best overall response
4. Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1 or first response defined by tumor marker change from baseline when RECIST evaluation is not feasible) to first occurrence of objective PD or death from any cause, whichever occurs first

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BioNTech Cell & Gene Therapies GmbH

Sponsor organisation

BioNTech Cell & Gene Therapies GmbH

Address

An Der Goldgrube 12, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

BioNTech Cell & Gene Therapies GmbH

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

BioNTech Cell & Gene Therapies GmbH

Contact name

Clinical Trial Information Desk

Third parties 11

Locations

3 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Unexpected events 2 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications