BNT324 + BNT327 for Lung Cancer

Recruiting at 20 trial locations

Overseen By BioNTech clinical trials patient information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioNTech SE

Must not be taking: B7-H3 therapy, Topoisomerase inhibitors

Disqualifiers: Hematologic toxicity, Locoregional treatment, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 87 months

594 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for individuals with advanced or progressive lung cancer, specifically small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). It examines how two drugs, BNT324 and BNT327, work together to combat cancer by targeting specific proteins that promote tumor growth. The study includes various groups to assess the treatment's effectiveness in different types of lung cancer, including cases unresponsive to other treatments or those that have relapsed. Ideal participants have advanced lung cancer that cannot be surgically removed and have not succeeded with other therapies. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that BNT327 is a promising treatment for lung cancer. In one study, patients experienced side effects similar to those from chemotherapy and immune therapy, indicating these side effects are somewhat expected and manageable.

Evidence suggests that BNT327 has been effective in lung cancer patients, even those who have undergone previous treatments. The combination of BNT324 and BNT327 is still under study for safety, but earlier findings provide insight into potential side effects.

Overall, while side effects are present, they are typical for treatments of this nature. The safety of the combination remains under investigation, but initial findings offer some reassurance about its potential tolerability. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BNT324 and BNT327 for lung cancer because they may offer new ways to tackle the disease. Unlike standard treatments such as chemotherapy and targeted therapies, which primarily focus on killing rapidly dividing cells or targeting specific genetic mutations, BNT324 and BNT327 have unique mechanisms. These treatments are designed to enhance the body's immune response to cancer cells, potentially leading to more effective and durable results. Additionally, their ability to target both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) subpopulations, particularly those without actionable genetic alterations, sets them apart from existing therapies. This innovative approach could provide new hope for patients who have limited treatment options.

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

Research suggests that BNT324 and BNT327 could be promising treatments for lung cancer. BNT324 targets a protein called B7-H3, which helps cancer cells hide, and delivers a drug to kill them. BNT327 blocks two substances, PD-L1 and VEGF, that help tumors grow and evade the immune system. Studies have shown that BNT327 alone was effective in treating small cell lung cancer when other treatments failed. In this trial, participants will receive a combination of BNT324 and BNT327, which might enhance their ability to fight advanced lung cancer. Early results indicate they work well together, making this combination worth further exploration. ^{1 2 3 5 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 advanced or relapsed lung cancer, both small cell (SCLC) and non-small cell types (NSCLC). It includes those who haven't had treatment before (1L) and those who have tried at least one other therapy (2L+). NSCLC participants can join regardless of PD-L1 expression levels. Those with AGA-positive NSCLC must have had targeted therapy prior.

Inclusion Criteria

I have NSCLC, am AGA negative, and need second-line treatment or beyond.

I have NSCLC, am AGA negative, and need second-line treatment or beyond.

I have small cell lung cancer and am in the first line of treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BNT324 in combination with BNT327 using a dose escalation design in Part 1 and at RP2D or RP2D-1 in Part 2

Up to 87 months

Safety Follow-up

Participants are monitored for safety after treatment

4-8 weeks

Long-term Survival Follow-up

Participants are monitored for overall survival and other long-term outcomes

Up to 87 months

What Are the Treatments Tested in This Trial?

Interventions

• BNT324
• BNT327

Trial Overview The study tests a new combination therapy using BNT324, an antibody-drug conjugate targeting B7-H3, alongside BNT327, which targets both PD-L1 and VEGF. The goal is to see how effective and safe this combo is for patients with different subtypes of advanced lung cancer.

How Is the Trial Designed?

Group I: Part 2 - Cohort 7: RP2D of BNT324 + BNT327 Experimental Treatment 2 Interventions

In SCLC, 1L

Group II: Part 2 - Cohort 6: RP2D of BNT324 + BNT327 Experimental Treatment 2 Interventions

In NSCLC AGA positive

Group III: Part 2 - Cohort 5: RP2D of BNT324 + BNT327 Experimental Treatment 2 Interventions

In subpopulation 2 of NSCLC AGA negative, 2L+

Group IV: Part 2 - Cohort 4: RP2D of BNT324 + BNT327 Experimental Treatment 2 Interventions

In subpopulation 2 of NSCLC AGA negative, 1L

Group V: Part 2 - Cohort 3: RP2D of BNT324 + BNT327 Experimental Treatment 2 Interventions

In subpopulation 1 of NSCLC AGA negative, 2L+

Group VI: Part 2 - Cohort 2: RP2D of BNT324 + BNT327 and RP2D-1 of BNT324 + BNT327 Experimental Treatment 2 Interventions

In SCLC, second-line plus (2L+)

Group VII: Part 2 - Cohort 1: RP2D of BNT324 + BNT327 and RP2D-1 of BNT324 + BNT327 Experimental Treatment 2 Interventions

In subpopulation 1 of NSCLC actionable oncogenic alteration (AGA) negative, first-line (1L)

Group VIII: Part 1 - BNT324 + BNT327 combination therapy Experimental Treatment 2 Interventions

Escalating combination dose levels of BNT324 and BNT327 to define RP2D and RP2D-1 for NSCLC and SCLC.

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+

DualityBio Inc.

Industry Sponsor

Trials

12

Recruited

5,800+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06892548

NCT06892548 | A Clinical Study to Investigate the Efficacy ... A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer.

2. clinicaltrials.biontech.com clinicaltrials.biontech.com/trials/BNT324-01?

A Clinical Study to Investigate the Efficacy and Safety of ... This study aims to investigate the combination of BNT324, a B7-H3 antibody-drug conjugate (ADC) with BNT327, a programmed death-ligand 1 (PD-L1) and vascular ...

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

Updated phase II efficacy and safety results of BNT327 ... BNT327 shows clinical activity as 2L treatment in SCLC, with adverse events consistent with chemo and IO treatment. Further evaluation in 2L SCLC is ongoing in ...

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/585976

A Clinical Study to Investigate the Efficacy and Safety of ... This study aims to investigate the combination of BNT324, a B7-H3 antibody-drug conjugate (ADC) with BNT327, a programmed death-ligand 1 ...

5. clinicaltrials.gov clinicaltrials.gov/show/NCT06892548

NCT06892548 | A Clinical Study to Investigate the Efficacy ... A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer.

6. 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/ ... At the August 7, 2025 data cut-off, among 38 efficacy-evaluable patients, the confirmed overall response rate was 76.3% (85.0% at 20 mg/kg [dose ...