BNT327 + Chemotherapy for Small Cell Lung Cancer

Recruiting at 8 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

439 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase III, multisite, randomized, double-blinded study to investigate BNT327 combined with chemotherapy (etoposide/carboplatin) compared to atezolizumab combined with chemotherapy (etoposide/carboplatin) for the treatment of participants with previously untreated extensive-stage small-cell lung cancer (ES-SCLC).

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.

What safety data exists for BNT327 + Chemotherapy for Small Cell Lung Cancer?

There is no specific safety data available for BNT327 in the provided research articles. However, other treatments for small cell lung cancer, like lurbinectedin, have shown an acceptable and manageable safety profile in patients with advanced solid tumors. ^{1 2 3 4 5}

What makes the drug BNT327 unique for treating small cell lung cancer?

The drug BNT327 is unique because it is being tested in combination with chemotherapy specifically for small cell lung cancer, which is a condition with limited long-term treatment success. While other treatments like belotecan and cisplatin are used, BNT327 may offer a novel approach, potentially improving outcomes by targeting the cancer differently. ^{5 6 7 8 9}

Research Team

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Arm 3 - BNT327 Dose 2 + Etoposide + Carboplatin Experimental Treatment 3 Interventions

Group II: Arm 2 - BNT327 Dose 1 + Etoposide + Carboplatin Experimental Treatment 3 Interventions

Group III: Arm 1 - Atezolizumab + Etoposide + Carboplatin Experimental Treatment 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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

Second-line treatment of small-cell lung cancer. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Multicenter phase II study of brequinar sodium in patients with advanced lung cancer. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Small cell lung cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. [2023]

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

Novel therapies for the treatment of small-cell lung cancer: a time for cautious optimism? [2018]

6. Germany 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. [2013]

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

Multicenter phase II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung cancer. [2017]

8. United States 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. [2013]

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

New agents in the treatment of small cell lung cancer. [2022]