BNT411 + Chemotherapy for Small Cell Lung Cancer

Recruiting at 13 trial locations

Overseen By BioNTech clinical trial information desk

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioNTech SE

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called BNT411, which helps the immune system fight cancer. It is being tested on patients with advanced cancers, including a specific type of lung cancer. BNT411 works by boosting the immune system's ability to attack cancer cells, especially when combined with other treatments.

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, you cannot have received certain treatments like radiotherapy, chemotherapy, or immunotherapy within a specific time before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination BNT411 + Chemotherapy for Small Cell Lung Cancer?

Research shows that adding atezolizumab to chemotherapy with carboplatin and etoposide significantly improves survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone, making it a valuable treatment option. ^{1 2 3 4 5}

Is the combination of BNT411, atezolizumab, carboplatin, and etoposide safe for humans?

The combination of atezolizumab (Tecentriq), carboplatin, and etoposide has been generally well tolerated in clinical trials for small cell lung cancer, with no new safety concerns beyond those known for the individual drugs. Common side effects included blood-related issues, skin rash, and low thyroid function, but it did not negatively affect patients' quality of life. ^{1 3 6 7 8}

What makes the drug BNT411 + Chemotherapy unique for small cell lung cancer?

The drug BNT411 + Chemotherapy is unique because it includes atezolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, combined with traditional chemotherapy drugs carboplatin and etoposide. This combination has been shown to improve survival rates in patients with extensive-stage small cell lung cancer compared to chemotherapy alone. ^{1 3 9 10 11}

Research Team

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Eligibility Criteria

This trial is for adults with ES-SCLC who haven't had chemo for it yet, or those with solid tumors without standard treatment options. Participants must be over 18, have a certain level of physical fitness (ECOG 0-1), and not have specific health issues like interstitial lung disease. They should also agree to use birth control if necessary and provide tissue samples.

Inclusion Criteria

I am 18 years old or older.

I am 18 years old or older.

I can provide a sample of my tumor preserved in paraffin.

Exclusion Criteria

I have a history of seizures, stroke, fluid drainage needs, eye issues, recent fever, or autoimmune diseases.

I have not had major surgery in the last 4 weeks.

My side effects from previous treatments are mild.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation - Monotherapy

First-in-human, open-label, dose-escalation trial studying BNT411 monotherapy in patients with solid tumors to determine the safety profile

21 days per cycle

Multiple visits per cycle

Dose Escalation - Combination Therapy

BNT411 in combination with atezolizumab, carboplatin, and etoposide in patients with chemotherapy-naïve ES-SCLC to determine safety profile

21 days per cycle

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years and 11 months

Treatment Details

Interventions

• Atezolizumab
• BNT411
• Carboplatin
• Etoposide

Trial Overview The trial tests BNT411 alone and combined with Atezolizumab, Carboplatin, and Etoposide in cancer patients. It's the first time this drug—a TLR7 agonist expected to boost immune responses—is being used in humans to find a safe dosage.

Participant Groups

Group I: Part 2 - expansion cohorts Experimental Treatment 4 Interventions

BNT411 either as monotherapy or in combination with atezolizumab, carboplatin, and etoposide. Please note that the sponsor decided not to continue with this part of this trial.

Group II: Part 1B - combination dose escalation Experimental Treatment 4 Interventions

BNT411 in combination with atezolizumab, carboplatin, and etoposide.

Group III: Part 1A - monotherapy dose escalation Experimental Treatment 1 Intervention

BNT411 monotherapy

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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

Findings from Research

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

In a study of 65 patients with extensive-disease small-cell lung cancer, the combination of atezolizumab, carboplatin, and etoposide showed a high response rate of 73.8%, with 80.5% in elderly patients (median age 74 years).

Despite some significant hematological toxicities, such as decreased neutrophil counts in 61.1% of elderly patients, the treatment demonstrated acceptable safety and efficacy, suggesting it could be a preferred standard treatment for elderly patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. Shiono, A., Imai, H., Wasamoto, S., et al.[2023]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

A phase I trial presented in 2015 indicates that rovalpituzumab tesirine, an experimental antibody-drug conjugate, shows potential effectiveness against recurrent small cell lung cancer, a type of cancer with limited treatment options.

This trial highlights the promise of rovalpituzumab tesirine as a new therapeutic approach for patients suffering from this challenging form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADC Shows Effectiveness in SCLC. [2015]

In a study of 124 patients with treatment-naïve, metastatic nonsquamous PD-L1-positive non-small cell lung cancer, the combination of atezolizumab with carboplatin and nab-paclitaxel showed significantly improved overall survival (19.9 months) and progression-free survival (8.5 months) compared to carboplatin and nab-paclitaxel alone (14.8 months and 5.1 months, respectively).

While the combination therapy had a higher incidence of manageable adverse events like neutropenia and anemia, it still demonstrated a tolerable safety profile, suggesting it could be an effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study. Xu, B., Cheng, H., Li, K., et al.[2023]

The FDA approved atezolizumab, a PD-L1 inhibitor, in combination with carboplatin and etoposide as a first-line treatment for small cell lung cancer, highlighting its role in enhancing therapy options.

This approval was supported by the phase III IMpower133 trial, which demonstrated that the addition of atezolizumab significantly improved both overall survival and progression-free survival in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Atezolizumab OK'd for SCLC. [2020]

In the IMpower133 study involving 394 patients with extensive-stage small-cell lung cancer, the addition of atezolizumab to carboplatin and etoposide significantly improved progression-free and overall survival without increasing the overall safety risks compared to the placebo.

While immune-related adverse events were more common in the atezolizumab group, the overall safety profile was comparable to the placebo, and patient-reported quality of life improved more significantly in the atezolizumab group, supporting its use as a new standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Mansfield, AS., Każarnowicz, A., Karaseva, N., et al.[2022]

Combination chemotherapy, particularly cisplatin plus etoposide, is the most effective first-line treatment for small cell lung cancer (SCLC), which accounts for 20% to 25% of lung cancer cases.

Concurrent thoracic radiotherapy during early chemotherapy significantly improves survival in limited-stage SCLC, and prophylactic cranial irradiation helps reduce brain recurrences with minimal long-term side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of small cell cancer of the lung. Adjei, AA.[2019]

In a study involving 403 patients with extensive-stage small-cell lung cancer, adding atezolizumab to carboplatin and etoposide significantly improved overall survival (OS) from 10.3 months to 12.3 months compared to placebo, indicating its efficacy as a first-line treatment.

The addition of atezolizumab showed a tolerable safety profile and provided benefits regardless of patients' PD-L1 or blood-based tumor mutational burden status, suggesting it can be effective across different patient biomarker profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). Liu, SV., Reck, M., Mansfield, AS., et al.[2022]

References

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

Atezolizumab: A Review in Extensive-Stage SCLC. [2021]

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

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

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

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. [2023]

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

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

ADC Shows Effectiveness in SCLC. [2015]

6. Germany pubmed.ncbi.nlm.nih.gov

Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study. [2023]

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

First-Line Atezolizumab OK'd for SCLC. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. [2022]

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

Management of small cell cancer of the lung. [2019]

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

Combination chemotherapy with carboplatin, etoposide, and vincristine as first-line treatment in small-cell lung cancer. [2017]

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

Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). [2022]