BNT116 + Standard Therapy for Non-Small Cell Lung Cancer

(LuCa-MERIT-1 Trial)

Recruiting at 56 trial locations

Overseen By BioNTech clinical trials patient information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BioNTech SE

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Active NSCLC treatment, 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

Duration: up to 27 months

280 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BNT116 for individuals with non-small cell lung cancer (NSCLC). The researchers aim to determine a safe dose and assess the effectiveness of BNT116 both alone and in combination with other approved cancer drugs. The study is open to those with advanced or metastatic NSCLC and specific conditions related to their cancer stage. Participants must have a diagnosis of NSCLC that is advanced, metastatic, or unresectable (cannot be removed by surgery). As a Phase 1 trial, this research focuses on understanding the treatment's effects 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 does not specify if you must stop taking your current medications, but ongoing active systemic treatment against NSCLC is not allowed. If you are on systemic steroid medication, it must be reduced to a low dose before starting the trial.

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

Research has shown that BNT116, a new cancer treatment, is currently undergoing testing to determine its safety for humans. This trial marks the first time BNT116 is being tested in people, with the primary goal of assessing its safety and identifying the correct dose. As this is early research, detailed safety information is not yet fully available.

BNT116 is being tested both alone and in combination with other treatments such as cemiplimab, docetaxel, and new antibodies. In other early studies, BNT116 combined with cemiplimab demonstrated a manageable safety profile, indicating that while some side effects occurred, they were generally not severe and could be managed. This offers hope for the treatment's safety in humans, though more data is needed for confirmation.

For combinations of BNT116 with other treatments like docetaxel and various antibodies, safety data is still being collected. Researchers are closely monitoring how participants handle these combinations. Since this trial is the first human test of BNT116, potential participants should know that the main aim is to understand any possible risks and how to manage them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BNT116 for non-small cell lung cancer because it targets the cancer cells differently from existing treatments. While standard treatments like chemotherapy and immunotherapy focus broadly on killing or inhibiting cancer cells, BNT116 uses a specific mechanism to enhance the immune system's ability to recognize and attack these cells. Furthermore, BNT116 is being tested in various combinations, including with antibodies and other drugs, to potentially increase its effectiveness against resistant or relapsed cancer. These innovative approaches offer hope for better outcomes and fewer side effects compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that BNT116, a vaccine using mRNA technology, is designed to help the immune system attack non-small cell lung cancer (NSCLC) cells. In this trial, participants may receive BNT116 in different combinations. Early results for BNT116 combined with cemiplimab indicate promising effects against tumors, with manageable side effects and good disease control in patients who did not respond to previous PD-1 treatments. In another arm, BNT116 is combined with docetaxel, and initial findings suggest this combination remains safe to use. Additionally, BNT116 is being tested with other experimental treatments, like anti-B7-H3 and anti-HER3 antibodies, to improve its effectiveness, though specific results for these combinations are still under study. The combination of BNT116 with a bispecific antibody targeting PD-L1 and VEGF-A is also being explored, based on evidence that these antibodies can produce strong responses in similar cancers. ^{1 2 5 6 7}

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 advanced or metastatic non-small cell lung cancer (NSCLC) who have not responded well to certain previous treatments. Specific groups include those with unresectable Stage III or metastatic Stage IV NSCLC, and some patients must have tried a PD-1/PD-L1 inhibitor therapy. Patients should be able to tolerate additional anti-PD-1 therapy and have an acceptable performance status.

Inclusion Criteria

I have NSCLC with PD-L1 expression ≥1% and cannot have chemotherapy as my first treatment.

My lung cancer is at Stage III and cannot be removed by surgery.

I have been treated with both a PD-1/PD-L1 inhibitor and platinum-based chemotherapy.

Exclusion Criteria

You have been on strong medications that weaken your immune system in the last 3 months before the trial.

I am on low-dose steroids or only take them as hormone replacement.

I am currently receiving treatment for non-small cell lung cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Dose confirmation and safety evaluation of BNT116 alone and in combination with other therapies in various cohorts

up to 27 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BNT116
• Cemiplimab
• Docetaxel

Trial Overview The trial tests BNT116 alone and in combination with cemiplimab or docetaxel for safety, tolerability, and preliminary effectiveness. It also explores BNT116 combined with chemotherapy as neo-adjuvant treatment before surgery followed by adjuvant BNT116 + cemiplimab in resectable cases.

How Is the Trial Designed?

Group I: Cohort 9: BNT116 + Anti-HER3 Antibody Conjugated to Topoisomerase I Inhibitor Experimental Treatment 2 Interventions

Dose confirmation for the combination of BNT116 with an anti-HER3 antibody conjugated to a topoisomerase I inhibitor with dose escalation of the anti-HER3 antibody conjugated to a topoisomerase I inhibitor

Group II: Cohort 8: BNT116 + Anti-B7-H3 Antibody Conjugated to Topoisomerase I Inhibitor Experimental Treatment 2 Interventions

Dose finding for the combination of BNT116 with an anti-B7-H3 antibody conjugated to a topoisomerase I inhibitor with dose escalation of the anti-B7-H3 antibody conjugated to a topoisomerase I inhibitor

Group III: Cohort 7 - BNT116 + BNT316 Experimental Treatment 2 Interventions

Dose finding for the combination of BNT116 with BNT316 (CTLA4 antibody) with dose escalation of BNT316

Group IV: Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel Experimental Treatment 4 Interventions

BNT116 + cemiplimab + carboplatin + paclitaxel as neo-adjuvant treatment followed by surgery, thereafter adjuvant treatment with BNT116 + cemiplimab

Group V: Cohort 5 - BNT116 + Cemiplimab (After Concurrent Chemoradiotherapy [CRT]) Experimental Treatment 2 Interventions

Group VI: Cohort 4 - BNT116 + Cemiplimab (Frail Participants) Experimental Treatment 2 Interventions

Group VII: Cohort 3 - BNT116 + Docetaxel Experimental Treatment 2 Interventions

Group VIII: Cohort 2 - BNT116 + Cemiplimab (PD-1/PD-L1 Inhibitor Refractory/Relapsed Participants) Experimental Treatment 2 Interventions

Group IX: Cohort 1B - BNT116 Monotherapy Experimental Treatment 1 Intervention

Group X: Cohort 1A - BNT116 Monotherapy Experimental Treatment 1 Intervention

Group XI: Cohort 11: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (After Concurrent CRT) Experimental Treatment 2 Interventions

Dose confirmation for BNT116 in combination with a bispecific antibody for PD-L1 and VEGF-A will be established in participants after concurrent CRT.

Group XII: Cohort 10: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (Frail Participants) Experimental Treatment 2 Interventions

Dose confirmation for BNT116 in combination with a bispecific antibody for programmed death ligand 1 (PD-L1) and vascular endothelial growth factor A (VEGF-A) will be established.

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

Amivantamab, an EGFR-MET bispecific antibody, shows promise as a standard treatment for EGFR-mutant non-small cell lung cancer, particularly when combined with chemotherapy for patients with exon 20 mutations.

In comparison to the standard treatment osimertinib, amivantamab combined with lazertinib improved progression-free survival, although this benefit came with increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFR-Mutant NSCLC: Spotlight on Amivantamab. [2023]

In a phase II trial involving 30 patients with advanced non-squamous non-small cell lung cancer (NSCLC), the combination of apatinib and docetaxel resulted in a disease control rate of 96.6% and a partial remission rate of 27.6%.

The treatment was found to be tolerable, with most adverse events being mild to moderate (grade 1-2), including hypertension and hand-foot syndrome, indicating that apatinib plus docetaxel is a safe option for patients with wild-type EGFR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of apatinib and docetaxel in treating advanced non-squamous non-small cell lung cancer patients with wild-type EGFR: a multi-center, phase II trial. Song, Y., Miao, L., Wang, Z., et al.[2022]

Switch maintenance therapy with pemetrexed or erlotinib has shown a significant improvement in overall survival for patients with advanced non-small cell lung cancer, while continuation maintenance with cetuximab and bevacizumab lacks demonstrated overall survival benefits and should be considered investigational.

Despite the potential benefits of maintenance therapy, Phase III trials have not shown improvements in quality of life, and a notable percentage of patients in placebo arms did not receive second-line therapy, highlighting the complexity of treatment decisions in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy in advanced non-small cell lung cancer: current status and future implications. Stinchcombe, TE., Socinski, MA.[2010]

EGFR inhibitors significantly improve objective response rates (ORR), disease control rates (DCR), and progression-free survival (PFS) in advanced non-small cell lung cancer patients with EGFR mutations compared to non-targeted chemotherapy, based on a review of 21 studies involving 4,250 patients.

Despite the improved response and control rates with EGFR inhibitors, overall survival (OS) did not show significant differences compared to non-targeted chemotherapy or older EGFR inhibitors, indicating that better short-term outcomes do not necessarily translate to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of EGFR Inhibitors in the Treatment of EGFRPositive NSCLC Patients: A Meta-Analysis. Dang, A., Dang, S., Vallish, BN.[2021]

In a study of 110 patients with advanced non-squamous non-small cell lung cancer, maintenance therapy with pemetrexed and bevacizumab showed a 1-year progression-free survival (PFS) rate of 43.9%, compared to 35.2% for pemetrexed alone, but this difference was not statistically significant (p = 0.433).

While both treatment regimens were feasible, the combination therapy had a higher incidence of mild side effects like nasal hemorrhage, hypertension, and proteinuria, indicating that while it may not offer significant clinical benefits over pemetrexed alone, it does come with additional risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy with pemetrexed and bevacizumab versus pemetrexed monotherapy after induction therapy with carboplatin, pemetrexed, and bevacizumab in patients with advanced non-squamous non small cell lung cancer. Karayama, M., Inui, N., Fujisawa, T., et al.[2022]

Targeted therapies for non-small cell lung cancer (NSCLC) have significantly improved treatment options, but their effectiveness can be compromised by issues like poor patient adherence and adverse events.

The review highlights the need for standardized monitoring protocols for the various toxicities associated with these therapies, which can include skin, gastrointestinal, lung, and heart-related side effects, to ensure better patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. Hines, JB., Bowar, B., Levine, E., et al.[2023]

Maintenance therapy for advanced nonsmall cell lung cancer can improve progression-free survival, with switch maintenance using pemetrexed or erlotinib showing the most clear clinical benefits.

Continuation maintenance with bevacizumab also improves progression-free survival, but the role of cetuximab remains unclear, highlighting the need to consider toxicity, quality of life, and cost in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of maintenance treatments for nonsmall cell lung cancer. Eadens, MJ., Robinson, SI., Price, KA.[2020]

The Checkmate-816 trial showed that combining neoadjuvant immunotherapy with platinum-based chemotherapy is effective for treating resectable non-small cell lung cancer, highlighting a promising approach in cancer therapy.

This trial reinforces the importance of personalized therapy and understanding the biology of lung cancer to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When immunotherapy meets surgery in non-small cell lung cancer. Herbst, RS., Wang, M., Chen, L.[2022]

A recent phase 3 trial demonstrated that adding immunotherapy to neoadjuvant chemotherapy significantly improves event-free survival in patients with non-small-cell lung cancer (NSCLC).

This trial marks the first positive results for phase 3 studies in the neoadjuvant setting for NSCLC, indicating a promising direction for future research on immunotherapy in combination with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant immunotherapy in non-small-cell lung cancer: Times are changing-and fast. Aguado, C., Maestre, UJ., Mielgo-Rubio, X.[2022]

The combination of BRAF and MEK inhibitors, specifically encorafenib and binimetinib, shows high antitumor activity in treating BRAF V600-mutant non-small cell lung cancer, with manageable side effects such as hypertension and mild gastrointestinal issues.

In a case study of a 70-year-old patient, drug-induced colitis was identified after treatment, but the condition resolved after treatment interruption, allowing the patient to resume therapy safely, highlighting the importance of monitoring for gastrointestinal toxicities even though they are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-induced colitis on BRAF and MEK inhibitors for BRAF V600E-mutated non-small cell lung cancer: a case report. Gelsomino, F., Di Federico, A., Tardio, ML., et al.[2022]

Citations

1. clinicaltrials.biontech.com clinicaltrials.biontech.com/trials/BNT116-01

Clinical Trial Evaluating the Safety, Tolerability and ... This first-in-human (FIH) trial for BNT116 aims to establish the safety profile and a safe dose for BNT116 monotherapy as well as for BNT116 in combination ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05142189

Study Details | NCT05142189 | Clinical Trial Evaluating the ... This first-in-human (FIH) trial for BNT116 aims to establish the safety profile and a safe dose for BNT116 monotherapy as well as for BNT116 in combination ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39957693/

Groundbreaking mRNA Lung Cancer Vaccine Trials BNT116 delivers tumor-specific genetic in-structions to the immune system, targeting non-small cell lung cancer (NSCLC), the most prevalent lung cancer subtype.

4. lungcancerstoday.com lungcancerstoday.com/post/data-on-rna-based-cancer-vaccine-plus-cemiplimab-for-nsclc-presented-at-aacr-2025

Data on RNA-Based Cancer Vaccine Plus Cemiplimab for ... Serious TRAEs occurred in 35% of patients, with 15% of those only related to BNT116 and 15% of those only related to cemiplimab, with no fatal ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05557591

NCT05557591 | A Trial to Learn How the Cancer Vaccine ... The study is focused on patients who have advanced non-small cell lung cancer (NSCLC). The aims of this study are to see how safe and tolerable BNT116 is in ...

6. investors.biontech.de investors.biontech.de/system/files-encrypted/nasdaq_kms/assets/2024/09/17/10-19-17/ESMO%202024_BNTX%20vFINAL.pdf

ESMO 2024 - BioNTech Patients with EGFR-mutated Non-Small Cell Lung Cancer (NSCLC). Yi-Long Wu, MD, (Lung Cancer Institute, Guangdong Province People's Hospital ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12346708/

B7-H3 in Cancer Immunotherapy—Prospects and Challenges In addition, in non-small cell lung carcinoma (NSCLC), B7-H3 expression was positively correlated with CD45+ immune cells, with increased expression ...