BNT152+153 for Cancer

No longer recruiting at 7 trial locations

Overseen By BioNTech clinical trial information desk

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BioNTech SE

Must not be taking: Steroids, Immunosuppressants, Antivirals, others

Disqualifiers: Active infection, Autoimmune disease, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and proper dosage of two new treatments, BNT152 (mRNA encoding native IL-7) and BNT153 (mRNA encoding native IL-2), for individuals with advanced solid tumors that cannot be surgically removed or have metastasized. Eligible patients must lack other standard treatments expected to help. The trial consists of two parts: the first tests each treatment individually, and the second tests them together to determine the optimal dose for future studies. Individuals with metastatic solid tumors and no other treatment options might be suitable candidates for the trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these new therapies.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are using certain treatments like investigational drugs, recent chemotherapy, or high-dose steroids. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that BNT152 and BNT153 are still undergoing tests to ensure human safety. BNT152 aims to strengthen the immune system by boosting T cell activity with IL-7, a protein crucial for immune health. BNT153 functions similarly but targets IL-2, another protein that aids T cells in fighting cancer.

In other studies, IL-7 has shown potential to improve immune responses. IL-2 has been used in cancer treatments before, but it can cause side effects at high doses, such as low blood pressure or flu-like symptoms. Monitoring these side effects is crucial as BNT153 undergoes testing.

Since this is an early-stage study, the primary goal is to determine the safe dosage of these treatments. This involves finding a dose that is effective without causing excessive side effects. Participants can feel reassured knowing that safety remains a top priority in these trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BNT152 and BNT153 because they represent a new wave of cancer treatment using mRNA technology. Unlike traditional chemotherapies that target rapidly dividing cells, these treatments are designed to stimulate the body's immune system to recognize and attack cancer cells more effectively. This targeted approach has the potential to reduce side effects and increase treatment precision. Moreover, by combining both BNT152 and BNT153, researchers aim to enhance the immune response, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for solid tumors?

This trial will evaluate BNT152 and BNT153, both as a combination and individually. Studies have shown that BNT152 and BNT153 work together to enhance the immune system's ability to fight cancer. BNT152 uses mRNA to produce a protein called IL-7, which aids certain immune cells in growing and functioning better against tumors. BNT153 uses mRNA to create IL-2, another protein that enhances immune cells' effectiveness in attacking cancer. Early research demonstrated that these proteins improve the immune response in mice with tumors. While these findings are promising, further research is needed to determine their effectiveness in humans with cancer. ^{2 5 6 7 8}

Who Is on the Research Team?

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that can't be surgically removed or have spread, and who've run out of standard treatment options. They must have a certain level of blood clotting ability, organ function, and agree to use effective birth control. Those with brain metastases may qualify if stable and not requiring steroids.

Inclusion Criteria

Your white blood cell count needs to be at least 3 billion cells per liter.

You have enough platelets in your blood, with a count of at least 100 billion per liter.

Able and willing to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions, and other requirements of the trial.

Exclusion Criteria

You are allergic to any part of the treatment being used in the trial.

My brain metastases are stable, and I'm not on acute steroids.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Dose Escalation

Group A: BNT153 monotherapy dose escalation until MTD or MAD is defined. Group B: BNT152 monotherapy dose escalation until MTD or OBD is defined.

Variable, until MTD/MAD/OBD is defined

Part 2: Dose Escalation

Dose escalation of BNT152+153 in patients with advanced solid malignancies until RP2D is defined. Includes Parts 2A, 2B, and 2C.

Variable, until RP2D is defined

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• BNT152
• BNT153

Trial Overview The trial is testing BNT152+153 in patients with various solid tumors. It's an early-phase study to determine safe dosage levels (Part 1) and then find the best dose for future studies (Part 2). Patients will receive either BNT152 or BNT153 alone first, followed by a combination of both.

How Is the Trial Designed?

Group I: Part 2C - BNT152+153 Experimental Treatment 2 Interventions

Escalating dose levels up to RP2D

Group II: Part 2B - BNT152+153 Experimental Treatment 2 Interventions

Escalating dose levels up to RP2D

Group III: Part 2A - BNT152+153 Experimental Treatment 2 Interventions

Escalating dose levels up to RP2D

Group IV: Part 2 - BNT152+153 - biomarker cohort Experimental Treatment 2 Interventions

Group V: Part 1 group B BNT152 Experimental Treatment 1 Intervention

Monotherapy dose escalation.

Group VI: Part 1 group A BNT153 Experimental Treatment 1 Intervention

Monotherapy dose escalation.

Who Is Running the Clinical Trial?

BioNTech SE

Lead Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Published Research Related to This Trial

In a study of 11 small cell lung cancer (SCLC) cell lines, 9 showed detectable IL-15 gene expression, indicating a potential role of this cytokine in SCLC biology.

A novel IL-15 mRNA isoform was identified, which includes an additional sequence that may represent a new alternative exon, suggesting that IL-15 could have unique functions in tumors that differ from its traditional 'IL-2-like' activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a novel interleukin-15 (IL-15) transcript isoform generated by alternative splicing in human small cell lung cancer cell lines. Meazza, R., Verdiani, S., Biassoni, R., et al.[2006]

The chicken interleukin-15 (IL-15) gene was successfully cloned and shown to produce a protein that supports the growth of activated T lymphocytes, indicating its potential role in immune response.

Chicken IL-15 is expressed in various tissues and its expression can be enhanced by T cell activation, suggesting it plays a significant role in T cell development and function in chickens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular and functional characterization of chicken IL-15. Choi, KD., Lillehoj, HS., Song, KD., et al.[2019]

In a mouse colon carcinoma model, the plasmid vector pHi2-spIL15-CMV-tat (L3) effectively overexpressed IL-15, leading to inhibited tumor growth and prolonged survival in tumor-bearing mice.

The study demonstrated that IL-15 can stimulate immune cell proliferation and has potential therapeutic effects, suggesting that gene transfer methods targeting IL-15 should be explored further for treating human cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of colon tumor growth by IL-15 immunogene therapy. He, X., Li, W., Wang, Y., et al.[2013]

The IL-15/IL-15Rα complex (IL-15cx) significantly enhances the expansion and function of CD8+ T cells compared to standard IL-15, showing promise in treating breast cancer in mouse models.

Systemic administration of IL-15cx moderately inhibits breast cancer growth and increases cytotoxic CD8 T cells, while intratumoral gene electrotransfer of IL-15cx leads to long-term survival benefits, indicating its potential as an effective immunotherapy for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-15/IL-15Rα Heterodimeric Complex as Cancer Immunotherapy in Murine Breast Cancer Models. Guo, S., Smeltz, RB., Nanajian, A., et al.[2021]

The study developed an oncolytic adenovirus (Ad-E2F/IL15) that incorporates the IL-15 gene, which enhances its antitumor effects by activating immune cells like natural killer (NK) cells and CD8(+) T cells.

Combining this engineered virus with cytotoxic T lymphocytes (CTL) resulted in a significantly stronger therapeutic effect against tumors compared to using either the virus or CTL alone, suggesting a promising new approach for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined therapy with CTL cells and oncolytic adenovirus expressing IL-15-induced enhanced antitumor activity. Yan, Y., Li, S., Jia, T., et al.[2018]

A new recombinant cell line (BaF3/mb15/RAE-1ε) was successfully created to co-express membrane-bound IL-15 and RAE-1ε, which are crucial for activating and proliferating immune cells like natural killer (NK) cells.

This engineered cell line demonstrated the ability to enhance NK cell proliferation and IFN-γ secretion, indicating its potential for advancing research in immune cell activation and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Construction of a plasmid for co-expression of mouse membrane-bound form of IL-15 and RAE-1ε and its biological activity. Qian, L., Ji, MC., Pan, XY., et al.[2011]

The study developed a novel delivery system (CLPP) for mRNA encoding IL-15, which effectively stimulated immune responses against colorectal cancer cells in vitro and showed promising results in vivo.

In murine models, the CLPP/mIL-15 complex achieved significant tumor inhibition rates of up to 70% in abdominal cavity metastasis, indicating both high efficacy and safety for colorectal cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient Colorectal Cancer Gene Therapy with IL-15 mRNA Nanoformulation. Lei, S., Zhang, X., Men, K., et al.[2021]

Interleukin-15 (IL-15) is a promising immunotherapy candidate that stimulates the immune system by enhancing the proliferation and activity of T cells, B cells, and natural killer (NK) cells, which are crucial for attacking tumors.

IL-15 does not activate immunosuppressive T regulatory cells (Tregs), making it a unique option for boosting immune responses against cancer without promoting immune suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-15 biology and its therapeutic implications in cancer. Steel, JC., Waldmann, TA., Morris, JC.[2021]

The recombinant IL7/IL15 fusion protein (rIL7/IL15) demonstrated greater antitumor activity compared to individual IL7 or IL15 in mouse models of melanoma and colon cancer, suggesting it may be a more effective treatment option.

The enhanced efficacy of rIL7/IL15 is likely due to its longer serum half-life and its ability to increase the infiltration of immune cells like T cells and dendritic cells into tumors, while also reducing regulatory T cells that can suppress immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Antitumor Activity of a Recombinant IL7/IL15 Hybrid Cytokine in Mice. Song, Y., Liu, Y., Hu, R., et al.[2020]

Vaccination using tumor cells that coexpress interleukin-15 (IL-15) and its receptor (IL-15Rα) significantly enhances immune responses against tumors, leading to inhibited tumor growth and improved survival in mice.

The study demonstrated that this vaccine platform not only increased the infiltration of immune cells like CD8(+) T and natural killer (NK) cells into tumors but also provided a survival advantage against unrelated breast cancer cells, suggesting its potential for broader applications in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer. Morris, JC., Ramlogan-Steel, CA., Yu, P., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10111960/

A systematic review of interleukin-2-based ... Phase 1 study of BNT153 + BNT152 (mRNA encoding native IL-7) in cancer patients (EE: 112 patients). ... BNT153 is a liposome-encapsulated messenger RNA (mRNA) ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1525001625002084

Clinical development of therapeutic mRNA applications BioNTech developed BNT152 and BNT153, which encode for long-lasting IL-2 and IL-7. These are currently being tested in a phase 1 clinical trial ...

3. cell.com cell.com/cell-reports/fulltext/S2211-1247(25)01130-1

Targeting an essential viral oncoprotein with an IL-7 ... IL-7-containing mRNA vaccines improved antigen-specific T cell expansion, memory differentiation, and tumor control. We propose that the ...

4. withpower.com withpower.com/trial/phase-1-5-2021-495fa

BNT152+153 for Cancer · Info for Participants This trial is testing two new drugs, BNT152 and BNT153, in patients with advanced solid tumors who have no other treatment options.

5. nature.com nature.com/articles/s41392-024-02002-z

Progress and prospects of mRNA-based drugs in pre- ... Targeted LNPs deliver mRNA encoding IL-15 superagonists to balance efficacy and toxicity in cancer therapy. Preprint at biorxiv https://doi ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10917577/

Harnessing the Power of IL-7 to Boost T Cell Immunity in ... IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell ...

7. investors.biontech.de investors.biontech.de/system/files-encrypted/nasdaq_kms/assets/2022/06/29/7-20-21/29062022%20BioNTech%20Innovation%20Series_vFINAL.pdf

Innovation Series - BioNTech Collaboration with Genentech. mRNA cancer vaccines. • Data from ... mRNA encoding IL-7. • Sensitizes T cells to IL2 & increases CD8+ and ...

8. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00104-4/fulltext

A systematic review of interleukin-2-based ... Phase 1 study of BNT153 + BNT152 (mRNA encoding native IL-7) in cancer patients (EE: 112 patients). Recruiting (first posted 14.01.2021), NA, CT.