BNT142 for Solid Tumors

Not currently recruiting at 23 trial locations

Overseen By BioNTech clinical trials patient information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioNTech SE

Must not be taking: Chemotherapy, Immunotherapy, Steroids, others

Disqualifiers: Infection, Brain metastases, Pregnancy, 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 a new treatment, BNT142 (an mRNA-encoded T-cell engager monoclonal antibody), for individuals with advanced tumors that cannot be surgically removed or have metastasized. Researchers aim to determine the safety and behavior of BNT142 in the body, specifically targeting tumors positive for Claudin 6, a protein present in some cancers. Candidates may include those with advanced ovarian, non-squamous lung, endometrial, or testicular cancer who have not responded to standard treatments. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking chemotherapy, molecularly-targeted agents, and immunotherapy at least 3 weeks before starting the study treatment. If you're on steroids, you must not exceed a daily dose equivalent to 10 mg of prednisone.

Is there any evidence suggesting that BNT142 is likely to be safe for humans?

Research has shown that BNT142 is generally safe, with side effects typically mild and not serious. Higher doses have shown promise in treating tumors, particularly ovarian cancer, with some patients experiencing tumor shrinkage and no major side effects.

Early studies on similar drugs, such as BNT142, also report excellent safety, suggesting BNT142 might have similar properties. Overall, current evidence suggests BNT142 is well-tolerated in humans, though further research is needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

BNT142 is unique because it targets specific proteins on cancer cells, which might make it more precise and potentially more effective than traditional chemotherapy that attacks both healthy and cancerous cells. Researchers are excited about this treatment because it employs a novel mechanism of action, possibly leading to fewer side effects and improved outcomes for patients with solid tumors. This innovative approach could represent a significant advancement in cancer treatment, offering new hope for those with tumors that are difficult to treat with existing therapies.

What evidence suggests that BNT142 might be an effective treatment for solid tumors?

Research has shown that BNT142, the investigational treatment for solid tumors with Claudin 6 (CLDN6)-positive markers, has shown promise in early trials. In past studies, BNT142 was generally safe and demonstrated some ability to fight tumors, particularly in CLDN6-positive ovarian cancer, where 7 patients experienced partial responses. This mRNA-based therapy employs a special type of antibody to help the immune system target cancer cells. However, results have varied, with some reports indicating less success in different types of solid tumors. Despite some uncertainty, the early signs of BNT142's potential to aid specific cancer types are encouraging. ^{1 2 6 7 8}

Who Is on the Research Team?

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Are You a Good Fit for This Trial?

This trial is for adults with solid tumors that are CLDN6-positive, metastatic or cannot be surgically removed. They must have tried all standard treatments without success and not received certain therapies within specific time frames before the trial. Pregnant or breastfeeding individuals, those with new brain metastases, or on high-dose steroids are excluded.

Inclusion Criteria

My tumor is CLDN6 positive based on a specific tissue test.

My cancer has spread or cannot be removed by surgery, confirmed by a pathology report.

I have advanced cancer and standard treatments haven't worked or aren't suitable for me.

Exclusion Criteria

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

I am not pregnant, breastfeeding, nor planning to become pregnant soon.

I haven't had cancer treatments like radiotherapy or chemotherapy in the last 3 weeks or more.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

First-in-human, open-label, dose escalation safety and PK study of BNT142 in patients with advanced/metastatic CLDN6-positive solid tumors

Duration not specified

Expansion

Phase IIa proof-of-concept study in expansion cohorts of CLDN6 positive advanced/metastatic ovarian cancer, NSCLC of non-squamous type, and testicular cancer patients

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• BNT142

Trial Overview The clinical trial is testing BNT142 in patients with advanced CLDN6-positive tumors. It's an early-phase study to determine safe dosage levels and initial effectiveness while monitoring how the body processes the drug across multiple centers.

How Is the Trial Designed?

Group I: BNT142 Experimental Treatment 1 Intervention

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 using immunocompetent mouse models, it was found that the density of tumor-associated T cells before treatment is crucial for the effectiveness of bispecific T cell engagers (BiTEs) in targeting 'cold' tumors.

The research identified that CD8+ T cells are key mediators of BiTE activity, while CD4+ T cells may hinder efficacy; combining BiTE therapy with immune checkpoint blockade (ICB) and 4-1BB agonism showed promise in enhancing treatment responses in tumors with low T cell infiltration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy combinations overcome resistance to bispecific T cell engager treatment in T cell-cold solid tumors. Belmontes, B., Sawant, DV., Zhong, W., et al.[2021]

A newly designed bispecific antibody targeting both CD3ε and PD-L1 showed enhanced antitumor immune responses in various tumor models compared to conventional bispecific T-cell engagers (BiTEs).

The mechanism of action involves rejuvenating CD8 T cells through blocking PD-L1 on dendritic cells, leading to more durable and effective T-cell responses, suggesting a promising approach for long-lasting cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rejuvenation of tumour-specific T cells through bispecific antibodies targeting PD-L1 on dendritic cells. Liu, L., Chen, J., Bae, J., et al.[2022]

Immunotherapy is emerging as a leading treatment for cancer, leveraging the body's immune system to combat tumors that have evaded immune detection.

Bispecific antibodies are highlighted for their ability to effectively recruit and activate immune cells against tumors, showing a strong safety profile and potential for use alongside other therapies like checkpoint inhibitors and cellular treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Antibodies to Arm Cytotoxic Lymphocytes in Cancer Immunotherapy. Koch, J., Tesar, M.[2020]

The study developed a novel bispecific antibody called the light T-cell engager (LiTE), which effectively recruits T-cells to target and kill EGFR-expressing cancer cells without causing unwanted T-cell activation or toxicity to non-target cells.

LiTEs were successfully produced in mammalian cells and demonstrated the ability to bind to their target antigens, indicating their potential for safe and effective use in gene-based immunotherapy for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies. Mølgaard, K., Harwood, SL., Compte, M., et al.[2019]

Immune cell engagers, such as the recently approved bispecific antibodies like mosunetuzumab and teclistamab, are showing great promise in treating hematological cancers by being more potent than traditional monoclonal antibodies.

The development of trispecific antibodies could further enhance treatment efficacy by targeting multiple tumor antigens or boosting immune cell functions, potentially transforming the approach to relapsed or refractory hematological malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies. Tapia-Galisteo, A., Álvarez-Vallina, L., Sanz, L.[2023]

TNB-928B is a novel T-cell engager designed to selectively target tumor cells overexpressing folate receptor alpha (FRα), minimizing damage to healthy tissues with low FRα expression, which enhances its safety profile.

In preclinical mouse models of ovarian cancer, TNB-928B demonstrated effective tumor clearance and T-cell activation while inducing minimal cytokine release, suggesting a favorable therapeutic window for treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A T-cell engaging bispecific antibody with a tumor-selective bivalent folate receptor alpha binding arm for the treatment of ovarian cancer. Avanzino, BC., Prabhakar, K., Dalvi, P., et al.[2022]

A new knock-in mouse model (hCD3E-epi) was developed to study the efficacy of human T-cell engagers (TCEs) in fully immunocompetent hosts, overcoming limitations of previous models that used immunodeficient mice.

In this model, TCEs targeting human CD3E demonstrated strong T-cell activation and nearly complete depletion of peripheral B cells for up to 7 days, indicating their potential effectiveness in treating hematological and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Humanization of a strategic CD3 epitope enables evaluation of clinical T-cell engagers in a fully immunocompetent in vivo model. Zorn, JA., Wheeler, ML., Barnes, RM., et al.[2022]

T cell engagers are promising for cancer treatment, but their effectiveness is limited by the challenge of targeting low-density tumor-associated antigens (TAAs) on cancer cells, which can lead to off-target toxicity.

Using the Wilms' tumor 1 (WT1) oncoprotein, the study found that the geometry of T cell engager design significantly affects their ability to form immunological synapses and kill cancer cells, highlighting the importance of optimizing these design parameters for better therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conformation-selective rather than avidity-based binding to tumor associated antigen derived peptide-MHC enables targeting of WT1-pMHC low expressing cancer cells by anti-WT1-pMHC/CD3 T cell engagers. Walseng, E., Wang, B., Yang, C., et al.[2023]

MUC12 is a promising therapeutic target for colorectal tumors due to its differential localization in tumor cells compared to normal cells, with a BiTE molecule showing effective T-cell-redirected lysis of MUC12-expressing cells in vitro.

In a toxicology study on cynomolgus monkeys, the MUC12 BiTE molecule was well-tolerated at lower doses, but higher doses caused gastrointestinal damage, indicating a risk of on-target toxicity that needs to be managed for effective antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Assessment of a MUC12-Targeted BiTE (Bispecific T-cell Engager) Molecule. Pham, E., Friedrich, M., Aeffner, F., et al.[2022]

The newly developed tetraspecific killer engager (TetraKE), named 1615EpCAM133, effectively targets both cancer stem cells and carcinoma cells, promoting enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and NK cell proliferation.

TetraKE demonstrated superior killing activity against cancer cells while maintaining a controlled cytokine response, suggesting it could be a promising therapeutic option for targeting drug-resistant cancer stem cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetraspecific scFv construct provides NK cell mediated ADCC and self-sustaining stimuli via insertion of IL-15 as a cross-linker. Schmohl, JU., Felices, M., Todhunter, D., et al.[2018]

In a study involving mice, the effectiveness of bispecific T cell engagers (BiTE) in targeting tumors is significantly affected by the level of tumor inflammation.

Higher T-cell infiltration into tumors enhances the response to BiTE therapy, suggesting that the immune environment plays a crucial role in the efficacy of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mouse Models Provide Insight into Factors Affecting BiTE Efficacy. [2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2501

First-in-human phase I/II trial evaluating BNT142, a first-in- ... BNT142 demonstrated a manageable safety profile and promising anti-tumor activity at the higher DLs, with 7 RECIST 1.1 PRs in CLDN6+ ovarian cancer.

2. oncologypipeline.com oncologypipeline.com/apexonco/biontech-quietly-drops-claudin6-work

BioNTech quietly drops Claudin6 work | ApexOnco Still, the future of BNT142 hangs in the balance after BioNTech reported disappointing data at ASCO in various Claudin6-positive solid tumours.

3. youtube.com youtube.com/watch?v=b5MV6V4alvs

Phase I/II trial of BNT142, an mRNA encoded bsAb, in ... These results provide first-in-human clinical proof-of-concept for mRNA-based bispecific antibody therapy in solid tumors. This interview ...

4. science.org science.org/doi/10.1126/scitranslmed.adl2720

Preclinical efficacy and pharmacokinetics of an RNA- ... Our study demonstrates that the mRNA-encoded CLDN6-targeting BsAb delivered by BNT142 displays a favorable pharmacokinetic (PK) profile in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11743637/

Effective cancer immunotherapy combining mRNA- ... Effective cancer immunotherapy combining mRNA-encoded bispecific antibodies that induce polyclonal T cell engagement and PD-L1-dependent 4-1BB costimulation.

6. withpower.com withpower.com/trial/phase-2-tumors-solid-2-2022-a8b0f

BNT142 for Solid Tumors · Info for Participants The research mentions that bispecific antibodies, which are similar to BNT142, have an excellent safety profile and are being developed for cancer treatment.

7. clinicaltrials.biontech.com clinicaltrials.biontech.com/trials/BNT142-01

Safety and Preliminary Efficacy Trial of BNT142 in Patients ... This study is an open-label, multicenter, Phase I/IIa, dose escalation, safety, and pharmacokinetics (PK) study of BNT142 followed by expansion cohorts.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05262530

Study Details | NCT05262530 | Safety and Preliminary ... This study is an open-label, multicenter, Phase I/IIa, dose escalation, safety, and pharmacokinetics (PK) study of BNT142 followed by expansion cohorts in ...