BNT327 + Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 151 trial locations

Overseen By BioNTech clinical trials patient information

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: BioNTech SE

Must not be taking: Anti-VEGF, PD(L)-1, Corticosteroids

Disqualifiers: Small-cell lung cancer, Uncontrolled hypertension, 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

982 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment, BNT327, combined with chemotherapy for individuals with advanced non-small cell lung cancer (NSCLC). Two treatment types are under evaluation, each paired with different chemotherapy drugs based on the specific NSCLC subtype. Suitable candidates for this trial have advanced-stage NSCLC that cannot be treated with surgery or radiation and have not received specific previous cancer treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to the development of potentially effective therapies.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received certain treatments like anti-VEGF monoclonal antibodies or high-dose corticosteroids shortly before starting the trial.

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

Research has shown that Pumitamig (also known as BNT327) is generally well-tolerated by patients with lung cancer. In a study involving patients with non-small cell lung cancer (NSCLC), Pumitamig combined with chemotherapy demonstrated an acceptable safety profile, meaning most side effects were manageable. Common side effects included tiredness and nausea, typical of cancer treatments. Importantly, no unexpected severe side effects were reported.

Pembrolizumab, another treatment in the study, has already received FDA approval for various cancers. It has a known safety profile, but like any treatment, it can cause side effects such as tiredness, skin rash, and mild to moderate diarrhea. Most patients manage these side effects with their healthcare team's support.

Both treatments have demonstrated promising safety records in studies, making them potential options for those considering joining this clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments involving BNT327 and Pumitamig for non-small cell lung cancer because they offer potential advancements over current therapies. BNT327 is unique because it targets cancer cells more precisely, potentially increasing effectiveness while reducing side effects compared to traditional chemotherapy. Pumitamig, another investigational drug, is being tested in combination with standard chemotherapy agents like carboplatin and pemetrexed or paclitaxel, and it may enhance the overall anti-cancer response. Unlike existing treatments, which primarily focus on broad mechanisms, these new approaches could provide a more targeted attack on cancer cells, offering hope for better outcomes in patients.

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

Research has shown that pumitamig (BNT327), a special type of antibody, holds promise for treating non-small cell lung cancer (NSCLC). In this trial, participants will receive different combinations of treatments. Some will receive pumitamig with chemotherapy agents such as Carboplatin and Pemetrexed or Paclitaxel. Earlier studies found pumitamig effective in shrinking tumors and generally well-tolerated by patients with advanced cancer. Specifically, patients who received this treatment experienced a noticeable decrease in tumor size, suggesting it could improve outcomes for those with NSCLC. Safety data indicates that while side effects are common, they can be managed. Overall, early evidence supports pumitamig as a hopeful option for NSCLC patients. ^{1 4 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 Stage IIIB/IIIC or IV non-small cell lung cancer (NSCLC) without certain genetic mutations. Participants should have at least one measurable lesion, be in good physical condition (ECOG 0-1), and have organs that are functioning well.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I have at least one cancer lesion that can be measured and has not been treated locally.

My organs are working well.

Exclusion Criteria

My lung cancer has been confirmed by lab tests to have a small-cell component.

I haven't taken high doses of steroids in the last 2 weeks.

My blood pressure or diabetes is not well-controlled.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2 Treatment

Participants are randomized to one of two dose levels of BNT327 plus chemotherapy

Up to approximately 2 years

Phase 3 Treatment

Participants receive the selected dose of BNT327 plus chemotherapy

Up to approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

What Are the Treatments Tested in This Trial?

Interventions

• BNT327
• Pembrolizumab

Trial Overview

The study tests BNT327 combined with chemotherapy drugs like Paclitaxel, Pemetrexed, Carboplatin, and Pembrolizumab. It's a Phase 2/3 trial with two parts based on NSCLC subtypes and includes standard treatments plus the new drug.

How Is the Trial Designed?

Group I: Substudy B Phase 3 - Pumitamig + Carboplatin + Paclitaxel Experimental Treatment 3 Interventions

Pumitamig selected dose for Phase 3

Group II: Substudy B Phase 2 - Pumitamig Dose 2 + Carboplatin + Paclitaxel Experimental Treatment 3 Interventions

Group III: Substudy B Phase 2 - Pumitamig Dose 1 + Carboplatin + Paclitaxel Experimental Treatment 3 Interventions

Group IV: Substudy A Phase 3 - Pumitamig + Carboplatin + Pemetrexed Experimental Treatment 3 Interventions

Pumitamig selected dose for Phase 3

Group V: Substudy A Phase 2 - Pumitamig Dose 2 + Carboplatin + Pemetrexed Experimental Treatment 3 Interventions

Group VI: Substudy A Phase 2 - Pumitamig Dose 1 + Carboplatin + Pemetrexed Experimental Treatment 3 Interventions

Group VII: Substudy B Phase 3 - Pembrolizumab + Carboplatin + Paclitaxel Active Control 3 Interventions

Group VIII: Substudy A Phase 3 - Pembrolizumab + Carboplatin + Pemetrexed Active Control 3 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

Biotheus Inc.

Industry Sponsor

Trials

21

Recruited

5,100+

Published Research Related to This Trial

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

Adjuvant platinum-based chemotherapy is the standard treatment for patients with resected non-small-cell lung cancer (NSCLC) stage IB to IIIA, but many still face disease recurrence, highlighting the need for more effective therapies.

The ALCHEMIST trial is investigating the efficacy of pembrolizumab, a PD-1 inhibitor, in combination with chemotherapy to potentially improve outcomes compared to standard chemotherapy alone, with the aim of reducing recurrence rates in NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO). Sands, JM., Mandrekar, SJ., Kozono, D., et al.[2022]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

In a study of 72 treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression, pembrolizumab showed an objective response rate of 45.8%, with even higher rates of 70.0% in patients with pre-existing interstitial lung disease (ILD).

Patients with ILD had similar overall survival rates compared to those without ILD, suggesting that pembrolizumab can be safely administered to NSCLC patients with ILD without compromising their prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. Yamaguchi, O., Kaira, K., Shinomiya, S., et al.[2021]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

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]

In a pooled analysis of 444 patients with PD-L1-negative advanced/metastatic non-small cell lung cancer (NSCLC), pembrolizumab combined with chemotherapy significantly improved overall survival (hazard ratio 0.63) and progression-free survival (hazard ratio 0.68) compared to chemotherapy alone.

Despite high rates of adverse events (99.2% in the pembrolizumab group), the combination therapy was manageable and resulted in an impressive objective response rate of 87.5% and a 3-year overall survival rate of 100% for patients completing 2 years of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer without tumor PD-L1 expression: A pooled analysis of 3 randomized controlled trials. Borghaei, H., Langer, CJ., Paz-Ares, L., et al.[2021]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved quality of life (QOL) compared to chemotherapy, with a notable increase in the global health status score by 6.9 points versus a decrease of 0.9 points for chemotherapy.

Patients treated with pembrolizumab experienced a longer time to deterioration in symptoms like cough and chest pain, with 31% showing deterioration compared to 39% in the chemotherapy group, indicating that pembrolizumab may be a preferable first-line treatment for patients with PD-L1-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Brahmer, JR., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

Citations

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Safety and Preliminary Effectiveness of BNT327, an ...

This is a Phase II, multisite, open-label, single arm study with two parts in participants with advanced/metastatic NSCLC which progressed after a first-line ...

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“Today's data add to the growing body of evidence indicating the potential of pumitamig to improve outcomes across a wide range of solid tumors, ...

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The NSCLC-SAQ is a 7-item patient-reported outcome measure for use in adults to assess symptoms of advanced non-small cell lung cancer. It contains five domains ...

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annalsofoncology.org/article/S0923-7534(24)02831-X/fulltext

1255MO A phase II safety and efficacy study of PM8002 ...

PM8002/BNT327 in combination with chemotherapy showed encouraging antitumor activity and acceptable tolerability profile in EGFR-mutated NSCLC patients that ...

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jto.org

jto.org/article/S1556-0864(25)00524-6/fulltext

Updated phase II efficacy and safety results of BNT327 ...

Treatment-related adverse events (TRAEs) of grade (G) ≥3 occurred in 78.6% of pts, most commonly neutrophil count decreased (64.3%) and low white blood cell ...

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A global phase 2/3, randomized, open-label trial of ...

This global Phase 2/3 trial will further assess safety and efficacy of BNT327 plus chemo (Phase 2) and BNT327 plus chemo versus pembrolizumab plus chemo (Phase ...