BNT411 + Chemotherapy for Small Cell Lung Cancer

No longer recruiting at 14 trial locations

Overseen By BioNTech clinical trial information desk

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioNTech SE

Must not be taking: Steroids, Cytochrome P450 drugs

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find a safe dose of a new treatment, BNT411, for small cell lung cancer. BNT411 is designed to enhance the immune system's response, particularly when combined with other cancer-fighting drugs like atezolizumab (Tecentriq), carboplatin, and etoposide. Patients with extensive-stage small cell lung cancer who have not yet received chemotherapy may be suitable candidates. The trial examines how BNT411 works both alone and in combination with these treatments. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this 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, 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.

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

Research has shown that BNT411, when used alone, is generally safe at all tested doses, with manageable and non-severe side effects. The treatment has also demonstrated potential in engaging the immune system, which is promising for cancer treatment.

Researchers are studying BNT411 in combination with other drugs like atezolizumab, carboplatin, and etoposide to assess its safety and effectiveness. Atezolizumab, already used in cancer treatment, has a well-established safety record from previous studies. The goal is to determine if BNT411 can enhance the effects of these existing treatments.

Overall, the trials aim to identify a safe dose for BNT411, both alone and in combination with these other drugs. For those considering joining a trial, it is reassuring that research so far suggests the side effects are manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BNT411 for small cell lung cancer because it offers a new approach by using a Toll-like receptor 7 (TLR7) agonist mechanism, which is designed to activate the immune system against cancer cells more effectively. Unlike the standard treatments like carboplatin and etoposide, which primarily aim to kill cancer cells directly, BNT411 aims to boost the body's immune response to target and destroy the cancer cells. Additionally, when combined with atezolizumab, an immune checkpoint inhibitor, BNT411 has the potential to enhance and prolong the immune system's ability to fight cancer, offering a promising new avenue for treatment.

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

Studies have shown that combining atezolizumab with carboplatin and etoposide can significantly improve outcomes for patients with small cell lung cancer. Atezolizumab, when added to these drugs, has helped patients live longer without cancer progression. This trial examines BNT411 both as a monotherapy and in combination with atezolizumab, carboplatin, and etoposide. Research indicates that BNT411, which activates the immune system, may enhance the effects of chemotherapy and immune therapies like atezolizumab. In early trials, one lung cancer patient experienced stable disease for five months with BNT411 alone. These findings suggest that BNT411 could be effective, particularly when combined with other treatments. ^{1 3 6 7 8}

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 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

This applies to both Part 1A and Part 1B of the study.

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

Your disease can be measured using a specific method called RECIST 1.1.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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]

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]

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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04101357

Study Details | NCT04101357 | Safety, Pharmacokinetics, ... This first-in-human (FIH) trial aimed to establish a safe dose of BNT411 as a monotherapy and in combination with atezolizumab, carboplatin and etoposide.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38377176/

Atezolizumab Plus Carboplatin and Etoposide in Patients ... Conclusions: Interim results provide further evidences about safety and efficacy profile of atezolizumab + carboplatin/etoposide treatment in a ...

3. jitc.bmj.com jitc.bmj.com/content/jitc/9/Suppl_2/A555.full.pdf

525 Preliminary safety, PK/PD and efficacy results from a ... Updated data will be presented, including combination treatment in the first-line setting of ES-. SCLC. Acknowledgements BNT411-01 is funded by BioNTech SE. The ...

4. withpower.com withpower.com/trial/phase-2-small-cell-lung-carcinoma-5-2020-c1e45

BNT411 + Chemotherapy for Small Cell Lung Cancer The combination of atezolizumab (Tecentriq), carboplatin, and etoposide has been generally well tolerated in clinical trials for small cell lung cancer, with no ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36800677/

Real-world evaluation of atezolizumab and etoposide ... The addition of atezolizumab to platinum-etoposide resulted in favorable outcomes in this real-world study.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38995324/

A DPC Database Study on the Safety of Atezolizumab ... This study provides evidence regarding the safety of ACE combination therapy in Japanese clinical practice using the DPC database.

7. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2019-003593-17/GB

Clinical Trials Register A study to investigate the safety and efficacy of BNT411 in cancer patients with solid tumor types. The study will also assess the safety and ...

8. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/first-in-human-bnt411-01-dose-escalation-with-expansion-cohorts/

First-in-human BNT411-01 dose-escalation with expansion ... BNT411-01 is an open-label, multicentre, dose-escalation, safety, pharmacokinetic (PK) and pharmacodynamics (PD) trial of BNT411 with expansion cohorts.