BNT314 +/- Immune Checkpoint Inhibitor for Cancer

Recruiting at 13 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: Corticosteroids, Immunosuppressants, others

Disqualifiers: Infection, Heart failure, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

360 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug, BNT314, alone and with pembrolizumab, in patients with advanced cancers who lack other treatment options. BNT314 aims to attack cancer cells directly, while pembrolizumab boosts the immune system's ability to fight cancer. Pembrolizumab has been shown to improve recurrence-free survival in various cancers and is approved for multiple indications.

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 have taken certain treatments like anticancer agents or investigational drugs within a specific time frame before starting the trial. It's best to discuss your current medications with the study team to see if they might affect your eligibility.

What data supports the effectiveness of the drug Pembrolizumab in cancer treatment?

Pembrolizumab, a drug that helps the immune system fight cancer, has shown effectiveness in treating advanced melanoma and certain types of lung cancer. It works by blocking a protein that prevents the immune system from attacking cancer cells, and has been approved for use in these conditions. ^{1 2 3 4 5}

What safety information is available for BNT314 and Pembrolizumab (Keytruda)?

Pembrolizumab (Keytruda) has been associated with some side effects, including fatigue, cough, nausea, and more serious immune-related effects like pneumonitis (lung inflammation), colitis (inflammation of the colon), and rare cases of type 1 diabetes. These side effects occur in a small percentage of patients and are generally outweighed by the benefits in treating certain cancers. ^{1 2 3 6 7}

What makes the drug BNT314 with Pembrolizumab unique for cancer treatment?

BNT314 combined with Pembrolizumab is unique because it targets the PD-1/PD-L1 pathway, enhancing the immune system's ability to fight cancer by blocking a mechanism that tumors use to hide from immune cells. Pembrolizumab, a part of this combination, is already known for its effectiveness in treating various cancers by boosting T-cell activity, making this combination potentially more effective in engaging the immune system against cancer. ^{1 2 8 9 10}

Research Team

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Eligibility Criteria

Adults over 18 with advanced solid tumors that have worsened after standard treatment or who can't tolerate such treatments. They must be able to consent, follow study procedures, and have a life expectancy of more than 3 months. Good physical condition (ECOG score of 0 or 1) and proper organ function are required. Women must test negative for pregnancy and agree to contraception; men also need to use contraception.

Inclusion Criteria

Have measurable disease according to RECIST v1.1

Have adequate coagulation function at screening

My blood tests show my bone marrow is working well.

Exclusion Criteria

Prolonged QTc interval at baseline of ≥470 milliseconds using Fridericia's QT correction formula

Known alcohol dependency within 6 months enrollment in this study

Planned enrollment in another study of an IMP, starting after Visit D1 and continuously until the last planned visit in this study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients receive escalating dose levels of BNT314 to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD).

Variable, until MTD/MAD is determined

Safety Run-In (SRI)

BNT314 is combined with pembrolizumab to test safety in a small group of participants.

Variable, until safety is confirmed

Expansion

BNT314 combined with pembrolizumab is administered to a larger group of participants to further assess safety and efficacy.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment.

Up to 3 years after first dose

Treatment Details

Interventions

• BNT314
• Pembrolizumab

Trial Overview The trial is testing BNT314's safety alone and combined with pembrolizumab in cancer patients. It has three parts: dose escalation to find the safest high dose, a safety run-in combining both drugs in a small group, followed by an expansion phase treating up to 199 patients with this combination.

Participant Groups

Group I: BNT314 Monotherapy Experimental Treatment 1 Intervention

Escalating dose levels and backfill cohorts

Group II: BNT314 + pembrolizumab Experimental Treatment 2 Interventions

The BNT314 starting dose for the SRI combination therapy will be one DL lower than the RP2D/MTD/maximum administered dose (MAD) determined from the 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

Genmab

Industry Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

Findings from Research

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

In a study of 59 patients with relapsed/refractory extranodal natural killer/T-cell lymphoma treated with pembrolizumab, the overall response rate was 40.7%, with 28.8% achieving a complete response, indicating its potential efficacy as a salvage therapy.

While pembrolizumab showed modest effectiveness, it was associated with some grade 3 or 4 adverse events in 20.3% of patients, with neutropenia being the most common, suggesting that while it can be beneficial, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. Lee, JY., Kwon, JH., Hur, JY., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]

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

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. [2023]