BNT327 + Chemotherapy for Small Cell Lung Cancer

Recruiting at 89 trial locations

Overseen By BioNTech clinical trials patient information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BioNTech SE

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

Disqualifiers: Combined histologies, Untreated brain metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 2

621 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, BNT327 (an experimental treatment), combined with chemotherapy to compare its effectiveness and side effects to another treatment, atezolizumab combined with chemotherapy, for individuals with extensive-stage small-cell lung cancer (ES-SCLC) who have not received prior treatment. The goal is to determine if BNT327 is more effective or has different side effects. Suitable candidates for this trial include those with ES-SCLC who have not undergone systemic therapy for this condition and have a measurable tumor. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like systemic corticosteroids above a specific dose and some other therapies must not have been taken recently. It's best to discuss your current medications with the trial team.

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

Research has shown that BNT327 has a manageable safety profile based on earlier studies. Specifically, when combined with paclitaxel, a chemotherapy drug, BNT327 was generally well-tolerated by patients with small cell lung cancer. Some side effects occurred, but they were usually manageable, allowing doctors to address them without serious issues.

In this trial, researchers are comparing BNT327 to atezolizumab. Atezolizumab, already approved for certain types of cancer, has a known safety record. This provides context for what to expect in terms of safety for BNT327, which remains under study.

Overall, the safety data so far suggests that BNT327 could be a promising option, though it may have side effects like any treatment. Clinical trial participants are closely monitored to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BNT327 for small cell lung cancer because it offers a new approach compared to current treatments. Most existing treatments, like chemotherapy with etoposide and carboplatin, work by attacking rapidly dividing cancer cells. However, BNT327 is an innovative treatment that targets specific markers on cancer cells, potentially leading to more precise and effective results. Additionally, BNT327 is being tested in combination with standard chemotherapy, which might enhance its overall effectiveness and offer improved outcomes for patients. This new mechanism and combination strategy are what make BNT327 a promising option in the fight against this aggressive cancer.

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

Research has shown that BNT327, a new treatment, may benefit people with extensive-stage small-cell lung cancer (ES-SCLC). In this trial, participants will receive different treatments: Arm 1 includes Atezolizumab with Etoposide and Carboplatin, while Arms 2 and 3 involve BNT327 at varying doses combined with Etoposide and Carboplatin. Earlier studies revealed that nearly half of the patients receiving BNT327 experienced significant tumor shrinkage. Additionally, 87.7% of patients achieved disease control, meaning their cancer did not worsen. These promising results suggest that BNT327 could improve outcomes for people with this aggressive lung cancer. Early data also indicate a manageable safety profile, potentially causing fewer or less severe side effects. ^{1 2 3 4 6}

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 untreated extensive-stage small-cell lung cancer (ES-SCLC). Participants must have confirmed ES-SCLC, be in good physical condition (ECOG status of 0 or 1), and have proper organ function. They should not have had previous systemic therapy for ES-SCLC, except those treated curatively for limited-stage SCLC who've been treatment-free for at least 6 months.

Inclusion Criteria

My blood counts and organ functions are within normal ranges.

My small cell lung cancer diagnosis is confirmed by lab tests.

I am fully active or have some restrictions but can still care for myself.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Induction

Participants receive BNT327 or Atezolizumab in combination with chemotherapy until disease progression or intolerable toxicity

Up to 2 years

Maintenance

Continuation of treatment with BNT327 or Atezolizumab in combination with chemotherapy until disease progression or intolerable toxicity

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 39 months

2 safety follow-up visits and survival follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• BNT327

Trial Overview The study compares BNT327 combined with chemotherapy drugs etoposide and carboplatin against the known drug Atezolizumab with the same chemo regimen. It's a Phase III trial where participants are randomly assigned to either group in a double-blinded manner, meaning neither they nor the researchers know who receives which treatment.

How Is the Trial Designed?

Group I: Stage 2 Treatment Arm - Pumitamig Dose 3 + Etoposide + Carboplatin Experimental Treatment 3 Interventions

Group II: Stage 1 Treatment Arm 2 - Pumitamig Dose 2 + Etoposide + Carboplatin Experimental Treatment 3 Interventions

Group III: Stage 1 Treatment Arm 1 - Pumitamig Dose 1 + Etoposide + Carboplatin Experimental Treatment 3 Interventions

Group IV: Stage 1 Control Arm - Atezolizumab + Etoposide + Carboplatin Active Control 3 Interventions

Group V: Stage 2 Control Arm - Atezolizumab + Etoposide + Carboplatin 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+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Oblimersen, an antisense oligonucleotide targeting the bcl-2 oncogene, has been safely combined with chemotherapy, showing potential for improving treatment outcomes in small-cell lung cancer.

While some new agents like bortezomib and anti-angiogenic strategies are under evaluation, only thalidomide has shown a survival benefit when added to chemotherapy, although it comes with significant toxicity concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapies for the treatment of small-cell lung cancer: a time for cautious optimism? Board, RE., Thatcher, N., Lorigan, P.[2018]

Combination chemotherapy regimens, such as cisplatin/etoposide and carboplatin/etoposide, have significantly improved response rates and median survival in patients with small cell lung cancer (SCLC), but long-term survival remains a challenge.

New agents like paclitaxel and gemcitabine show promise in preliminary studies for untreated SCLC, and ongoing research is evaluating their effectiveness in combination with established treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New agents in the treatment of small cell lung cancer. Ghaemmaghami, M., Jett, JR.[2022]

Topotecan is currently the only FDA-approved second-line treatment for small-cell lung cancer, which is crucial since most patients relapse after initial therapy despite a high response rate of up to 90%.

While other agents like vinorelbine and irinotecan have shown modest efficacy, recent research has focused on optimizing topotecan dosing and exploring combination therapies, balancing increased activity with the need to manage toxicity and maintain quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line treatment of small-cell lung cancer. MacCallum, C., Gillenwater, HH.[2019]

In a study of 53 patients with advanced lung cancer, brequinar sodium showed limited efficacy, with only one objective response in non-small-cell (NSC) and two in small-cell (SC) cancer patients, suggesting it may not be effective enough for further testing in these groups.

Despite moderate toxicity, with 36% of patients experiencing severe side effects, the observed responses in previously treated SC patients indicate that brequinar could be worth investigating further in chemotherapy-naive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II study of brequinar sodium in patients with advanced lung cancer. Maroun, J., Ruckdeschel, J., Natale, R., et al.[2019]

Small cell lung cancer (SCLC) is highly sensitive to chemotherapy and radiation, with the standard treatment being a combination of platinum and etoposide, which is more effective when combined with thoracic radiotherapy (TRT), increasing survival by about 5%.

Prophylactic cranial radiation can prevent central nervous system recurrence and improve survival, while other novel agents like bevacizumab are showing promise and are under further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small cell lung cancer. Sher, T., Dy, GK., Adjei, AA.[2022]

The combination of belotecan and cisplatin as first-line chemotherapy for extensive disease small cell lung cancer (ED SCLC) demonstrated a high objective response rate of 71.4% among 30 evaluable patients, indicating significant efficacy in treating this aggressive cancer.

The treatment was associated with manageable safety profiles, with the most common severe side effects being hematologic (like neutropenia), while non-hematologic toxicities were minimal, suggesting a favorable balance between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of combined belotecan and cisplatin as first-line chemotherapy in patients with extensive disease of small cell lung cancer. Hong, J., Jung, M., Kim, YJ., et al.[2013]

Lurbinectedin has a manageable safety profile when used at the approved dose of 3.2 mg/m2 every 3 weeks, as shown in a pooled analysis of 554 patients with various advanced solid tumors, including small cell lung cancer and ovarian cancer.

The most common side effects were transient hematological abnormalities, particularly neutropenia (41%) and leukopenia (30%), along with non-hematological issues like fatigue (63%) and nausea (57%), indicating that while side effects are present, they are generally manageable for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. Leary, A., Oaknin, A., Trigo, JM., et al.[2023]

The addition of paclitaxel to cisplatin/etoposide chemotherapy and concurrent thoracic radiotherapy in patients with limited-stage small-cell lung cancer resulted in a high overall response rate of 92%, with 81% achieving complete remission, indicating strong efficacy of this treatment regimen.

While the treatment was effective, it was associated with significant hematologic toxicity, including severe leukopenia in 74% of patients and one treatment-related death, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung cancer. Bremnes, RM., Sundstrøm, S., Vilsvik, J., et al.[2017]

In a study involving 30 chemotherapy-naive patients with extensive-disease small cell lung cancer, the combination of belotecan and cisplatin resulted in a promising response rate of 70%, with a median overall survival of 19.2 months.

While the treatment was associated with some significant adverse events, such as neutropenia and a treatment-related death from pneumonia, most nonhematologic side effects were mild and manageable, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase 2 study of belotecan, a new camptothecin analog, and cisplatin for chemotherapy-naive patients with extensive-disease small cell lung cancer. Lee, DH., Kim, SW., Suh, C., et al.[2013]

Citations

1. investors.biontech.de investors.biontech.de/news-releases/news-release-details/first-disclosure-global-interim-phase-2-data-biontech-and

Press Release - BioNTech “Small cell lung cancer is the most aggressive type of lung cancer with rapid growth, a poor prognosis and 5-year relative survival rate of just ...

2. news.bms.com news.bms.com/news/corporate-financial/2025/First-Disclosure-of-Global-Interim-Phase-2-Data-for-BioNTech-and-Bristol-Myers-Squibb-PD-L1xVEGF-A-Bispecific-Antibody-Pumitamig-BNT327-BMS986545-in-Patients-with-Extensive-Stage-Small-Cell-Lung-Cancer-Shows-Encouraging-Antitumor-Activity/default.aspx

PD-L1xVEGF-A bispecific antibody pumitamig (BNT327/ ... “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, ...

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

Updated phase II efficacy and safety results of BNT327 ... After a median follow up of 17.9 mo (95% CI 15.7, 23.1), confirmed ORR was 41.5% (95% CI 29.4, 54.4), disease control rate 87.7% (95% CI 77.2, 94.5), median ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS8129

A global phase III, double-blind, randomized trial of ... Preliminary results from a Phase II trial showed encouraging efficacy results and a manageable safety profile for BNT327 with paclitaxel as ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06449209

Study Details | NCT06449209 | Safety, Preliminary ... This study will assess the safety, efficacy, and pharmacokinetics (PK) of BNT327. Detailed Description. In Cohort 1 of this study, two dose levels of BNT327 ...

6. investors.biontech.de investors.biontech.de/static-files/5ab86f78-41ac-4c94-85b9-7ec7cbb7a88c

Phase 2 study of the efficacy and safety of BNT327/PM8002 ... Updated phase II efficacy and safety results of BNT327/PM8002 combined with paclitaxel as second-line (2L) therapy in small cell lung cancer (SCLC). Trial ...