BNT142 for Solid Tumors

Recruiting in Palo Alto (17 mi)

+22 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: BioNTech SE

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

Disqualifiers: Infection, Brain metastases, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests BNT142, an experimental drug, on patients with advanced cancers that have a specific protein (CLDN6). The drug aims to help the immune system target and destroy these cancer cells.

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.

What data supports the effectiveness of the treatment BNT142 for solid tumors?

Research on similar treatments, like bispecific T cell engagers (BiTEs), shows they can help the immune system attack cancer cells in solid tumors. Studies suggest that these treatments work better when combined with other therapies that boost immune response, especially in tumors that don't naturally attract many immune cells. ^{1 2 3 4 5}

What safety data exists for BNT142 or similar treatments in humans?

The research mentions that bispecific antibodies, which are similar to BNT142, have an excellent safety profile and are being developed for cancer treatment. However, some bispecific T-cell engagers have shown severe toxicity at therapeutic doses in solid tumors, indicating potential safety concerns. ^{4 5 6 7 8}

What makes the drug BNT142 unique for treating solid tumors?

BNT142 is a novel treatment that uses mRNA technology to encode a T-cell engager, which helps the immune system target and destroy cancer cells more effectively. This approach is different from traditional treatments because it directly recruits T-cells to attack the tumor, potentially offering a more targeted and potent response against solid tumors. ^{1 4 9 10 11}

Research Team

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• BNT142 (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Immunotherapy combinations overcome resistance to bispecific T cell engager treatment in T cell-cold solid tumors. [2021]

2. Switzerland 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. [2023]

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

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

4. United States 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. [2022]

5. England 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Rejuvenation of tumour-specific T cells through bispecific antibodies targeting PD-L1 on dendritic cells. [2022]

7. United States 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. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Recombinant Antibodies to Arm Cytotoxic Lymphocytes in Cancer Immunotherapy. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies. [2019]

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

Preclinical Assessment of a MUC12-Targeted BiTE (Bispecific T-cell Engager) Molecule. [2022]