BNT111 + Cemiplimab for Melanoma

Not currently recruiting at 71 trial locations

Overseen By BioNTech clinical trial information desk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BioNTech SE

Must be taking: Anti-PD-1/PD-L1

Must not be taking: Systemic immunosuppressants, Steroids

Disqualifiers: Pregnancy, Autoimmune disease, Cardiovascular, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, BNT111 and cemiplimab (an immunotherapy drug), for individuals with advanced melanoma unresponsive to previous treatments. The researchers aim to assess the effectiveness and safety of these treatments, both individually and in combination. The trial targets those with unresectable Stage III or IV melanoma who have experienced disease progression despite prior immune therapies. Participants should have melanoma that cannot be surgically removed and has worsened after other treatments. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use systemic immune suppression medications or have had recent cancer treatments like chemotherapy or radiotherapy before starting the trial.

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

Research has shown that BNT111 is generally well-tolerated, with most participants experiencing only mild to moderate flu-like symptoms. No major side effects required stopping the treatment.

Cemiplimab, already approved by the FDA for other uses, is generally considered safe. Some patients experienced immune-related side effects, which were mostly manageable. Serious side effects, such as inflammation of the colon, were rare and led to treatment discontinuation in less than 1% of cases.

When combined, BNT111 and cemiplimab demonstrated a safety profile similar to their individual studies. No major new safety concerns emerged from their combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for melanoma, which often include surgery, radiation, and chemotherapy, the investigational treatments BNT111 and cemiplimab offer a unique approach. BNT111 is designed to trigger the immune system to specifically target melanoma cells by recognizing certain cancer-related antigens, essentially training the body to fight the cancer on its own. Cemiplimab, on the other hand, is a type of immunotherapy called a PD-1 inhibitor, which blocks a pathway that tumors use to hide from the immune system. Researchers are excited about these treatments because they harness the body's natural defenses, potentially offering a more targeted and less invasive option compared to traditional therapies.

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

Research has shown that combining BNT111 and cemiplimab, one of the treatment arms in this trial, may help treat melanoma that hasn't responded to other treatments. Studies found that 18.1% of patients responded positively to this combination, which is encouraging. Another arm in this trial will test BNT111 alone, which has also significantly improved response rates in melanoma patients. Cemiplimab by itself, tested in a separate arm, has a strong record of reducing the risk of melanoma and other skin cancers returning. These results suggest that both treatments, whether used alone or together, could effectively manage advanced melanoma. ^{2 3 4 5 6}

Who Is on the Research Team?

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Are You a Good Fit for This Trial?

Adults with advanced melanoma that has worsened despite anti-PD-1/PD-L1 therapy can join this trial. They must have good liver, kidney, and bone marrow function, no other cancers in the last 2 years, not be pregnant or breastfeeding, and agree to use birth control. Excluded are those with certain severe illnesses or conditions, recent treatments or surgeries incompatible with the trial's requirements.

Inclusion Criteria

Women of childbearing potential must have a negative pregnancy test at the start of the study.

Any initial signs of disease getting worse on a scan need to be confirmed by a specialized group of experts.

My liver is functioning well.

Exclusion Criteria

Presence of a severe concurrent illness or other condition that does not permit adequate follow-up and compliance with the protocol

I do not have any known immune system deficiencies.

You have recently developed or growing cancer in your brain or spine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BNT111 and/or cemiplimab based on randomization. Patients in single agent arms may switch to combination therapy upon disease progression.

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 48 months

What Are the Treatments Tested in This Trial?

Interventions

• BNT111
• Cemiplimab

Trial Overview

The study is testing BNT111 and Cemiplimab together and separately in people whose melanoma hasn't responded to standard treatments. Participants will be randomly assigned to receive both drugs combined or just one of them alone. If a single drug doesn't work, they might get the chance to try adding the other after agreeing again.

How Is the Trial Designed?

Group I: Cemiplimab monotherapy Experimental Treatment 1 Intervention

Group II: BNT111 monotherapy Experimental Treatment 1 Intervention

Group III: BNT111 + cemiplimab Experimental Treatment 2 Interventions

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

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

The FDA approved two groundbreaking drugs for malignant melanoma in 2011, marking a significant advancement in treatment after a 13-year gap, specifically ipilimumab for immune checkpoint modulation and targeted therapies like vemurafenib and dabrafenib for BRAF(V600) mutations.

These new therapies have changed the landscape of melanoma treatment, but they also raise important questions about how to best combine and sequence these agents for patients with BRAF mutant melanoma to enhance efficacy and manage resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab, vemurafenib, dabrafenib, and trametinib: synergistic competitors in the clinical management of BRAF mutant malignant melanoma. Luke, JJ., Hodi, FS.[2021]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Citations

1.

onclive.com

onclive.com/view/phase-2-bnt111-cemiplimab-data-prove-positive-in-pd--l-1-relapsed-refractory-melanoma

Phase 2 BNT111/Cemiplimab Data Prove Positive in PD-(L ...

BNT111 plus cemiplimab achieved an 18.1% ORR in PD-(L)1–refractory melanoma, meeting its primary end point in the phase 2 BNT111-01 trial.

2.

investors.biontech.de

investors.biontech.de/news-releases/news-release-details/biontech-announces-positive-topline-phase-2-results-mrna

Press Release - BioNTech

The trial met its primary efficacy outcome measure, demonstrating a statistically significant improvement in ORR in patients treated with BNT111 ...

3.

fiercebiotech.com

fiercebiotech.com/biotech/biontech-fades-out-further-work-fixvac-vaccine-prospect-advanced-melanoma-setting

BioNTech fades cancer vax in late-stage melanoma setting

In the study, investigators recorded an objective response rate (ORR) of 18.1% for patients who were treated with the BNT111 and Libtayo regimen ...

4.

aimatmelanoma.org

aimatmelanoma.org/update-on-the-state-of-vaccines-for-melanoma/

Update on the State of Vaccines for Melanoma

There was also a trend for improved overall survival to 96.0% versus 90.2% with pembrolizumab alone. A Phase III trial (NCT05933577) is ongoing ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04526899

NCT04526899 | A Study to Investigate the Novel Agent ...

This is an open-label, randomized, multi-site, Phase II, interventional trial designed to evaluate the efficacy, tolerability, and safety of BNT111 + cemiplimab

6.

investors.biontech.de

investors.biontech.de/news-releases/news-release-details/biontech-publishes-data-mrna-based-bnt111-fixvac-melanoma-trial

BioNTech Publishes Data from mRNA-based BNT111 FixVac ...

Overall, BNT111 treatment was well tolerated with no dose limiting toxicity. Most common adverse events were mild to moderate, transient flu- ...