BNT152+153 for Cancer

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

86 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two new drugs, BNT152 and BNT153, in patients with advanced solid tumors who have no other treatment options. The goal is to find the safest and most effective dose by adjusting the amount given to patients over time.

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.

What data supports the effectiveness of the BNT152+153 treatment for cancer?

Research on similar treatments shows that using mRNA to deliver cytokines like IL-15 can effectively stimulate the immune system to fight cancer, as seen in studies with colorectal and breast cancer models. This suggests that mRNA-based therapies, like BNT152+153, which encode for immune-stimulating proteins, may have potential in treating cancer by enhancing the body's immune response. ^{1 2 3 4 5}

What makes the BNT152+153 drug unique for cancer treatment?

The BNT152+153 drug is unique because it uses mRNA to encode native IL-7 and IL-2, which are proteins that can boost the immune system's ability to fight cancer. This approach is different from traditional cancer treatments as it directly enhances the body's immune response rather than targeting the cancer cells themselves. ^{6 7 8 9 10}

Research Team

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Eligibility Criteria

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 am HIV positive with a CD4+ count below 350 and have had AIDS-related infections.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficient Colorectal Cancer Gene Therapy with IL-15 mRNA Nanoformulation. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

IL-15/IL-15Rα Heterodimeric Complex as Cancer Immunotherapy in Murine Breast Cancer Models. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Interleukin-15 biology and its therapeutic implications in cancer. [2021]

5. Greece pubmed.ncbi.nlm.nih.gov

Inhibition of colon tumor growth by IL-15 immunogene therapy. [2013]

6. England 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. [2006]

7. United States pubmed.ncbi.nlm.nih.gov

Molecular and functional characterization of chicken IL-15. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

In Vivo Antitumor Activity of a Recombinant IL7/IL15 Hybrid Cytokine in Mice. [2020]

9. United States 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. [2011]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Combined therapy with CTL cells and oncolytic adenovirus expressing IL-15-induced enhanced antitumor activity. [2018]