BNT326 + BNT327 for Lung Cancer

Recruiting at 1 trial location

Overseen By BioNTech clinical trials patient information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioNTech SE

Must be taking: EGFR TKI

Must not be taking: HER3 agents

Disqualifiers: Active infection, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 24 months

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of combining two experimental treatments, BNT326 and BNT327, for patients with advanced or metastatic non-small cell lung cancer (NSCLC). It tests various treatment combinations and compares them to existing therapies like pembrolizumab (a type of immunotherapy) and chemotherapy. Patients diagnosed with advanced NSCLC, whether newly diagnosed or previously treated, may qualify if they haven't responded to or cannot receive standard treatments. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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

If you are taking an EGFR TKI (a type of targeted cancer therapy), you can continue it until 5 days before starting the trial treatment. For other medications, the trial protocol does not specify, so it's best to discuss with the trial team.

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

Previous studies have shown that patients generally tolerate the combination of BNT326 and BNT327 well. Researchers have found that the side effects of this combination resemble those typically seen with chemotherapy and immune therapy. Common side effects may include tiredness, nausea, or loss of appetite, but these are expected.

For BNT327 alone, studies indicate it is safe to use with chemotherapy, with most side effects being manageable and not severe. Early research suggests that BNT326 alone is safe for patients with cancers that have returned or grown despite treatment.

Since these treatments are still in the early testing stages, monitoring for any unexpected side effects is important. However, the results so far are promising in terms of safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BNT326 and BNT327 for lung cancer because these treatments offer a novel approach compared to current options like pembrolizumab and chemotherapy. Unlike standard treatments that often focus on generic mechanisms, BNT326 and BNT327 are designed as a combination therapy specifically targeting unique pathways in non-small cell lung cancer (NSCLC). This could potentially lead to more personalized and effective treatment outcomes, especially for patients with specific genetic markers like high PD-L1 expression or actionable mutations. Additionally, the ability to use these treatments in various patient profiles, including those with different stages and genetic backgrounds of NSCLC, sets them apart from the more one-size-fits-all standard therapies.

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

Research has shown that the combination of BNT326 and BNT327, which participants in this trial may receive, could help treat non-small cell lung cancer (NSCLC). Early results suggest that this combination can shrink or control tumors. Studies also indicate that the side effects are manageable and considered acceptable. In this trial, some participants will receive BNT327 monotherapy, while others will receive BNT326 monotherapy. Additionally, BNT327, when combined with treatments like chemotherapy, has shown positive results in other types of lung cancer. These early findings offer hope that BNT326 and BNT327 could be effective for individuals with advanced or hard-to-treat NSCLC. ^{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?

Adults with advanced non-small cell lung cancer (NSCLC), either metastatic or recurrent, who have relapsed after standard treatment or couldn't tolerate it. They must be at least 18 years old, able to provide a tumor tissue sample, and have an acceptable level of health apart from their cancer.

Inclusion Criteria

I meet the specific requirements for my study group.

I am 18 years old or older.

My cancer can be measured by standard health scans.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy of BNT326 and BNT327, with dose escalation and expansion to evaluate safety, efficacy, and pharmacokinetics

up to 24 months

Safety Follow-up

Participants are monitored for safety after treatment completion

approximately 90 days post last IMP dose

Efficacy Follow-up

Participants are monitored for efficacy outcomes such as objective response rate and progression-free survival

up to 36 months

Long-term Survival Follow-up

Participants are monitored for overall survival and long-term outcomes

up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• BNT326
• BNT327

Trial Overview The trial is testing a new combination therapy using BNT326 and BNT327 in people with NSCLC. It's an open-label study that will determine the safety and potential benefits of these drugs compared to the current standard of care (SoC) including Pembrolizumab.

How Is the Trial Designed?

Group I: Part 2b (Cohort D2, Arm 1) - BNT326 (DL2) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%.

Group II: Part 2b (Cohort D1, Arm 3) - BNT327 monotherapy Experimental Treatment 1 Intervention

BNT327 monotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%.

Group III: Part 2b (Cohort D1, Arm 1) - BNT326 (DL2) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%.

Group IV: Part 2b (Cohort C, Arm 3) - BNT326 monotherapy Experimental Treatment 1 Intervention

BNT326 monotherapy (DL2). In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1.

Group V: Part 2b (Cohort C, Arm 2) - BNT326 (DL2) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1.

Group VI: Part 2b (Cohort C, Arm 1) - BNT326 (DL1) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or epithelial growth factor receptor (EGFR) activating mutation, any PD-L1.

Group VII: Part 2a (Cohort B, Arm 2) - BNT326 (DL2) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with 1L squamous or non-squamous NSCLC, AGA-negative, any PD-L1.

Group VIII: Part 2a (Cohort B, Arm 1) - BNT326 (DL1) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with first-line (1L) squamous or non-squamous NSCLC, AGA-negative, any PD-L1.

Group IX: Part 2a (Cohort A, Arm 2) - BNT326 (DL2) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1.

Group X: Part 2a (Cohort A, Arm 1) - BNT326 (DL1) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1.

Group XI: Part 1 - BNT326 (DL3, optional) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1.

Group XII: Part 1 - BNT326 (DL2) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1.

Group XIII: Part 1 - BNT326 (DL1, starting dose) + BNT327 Experimental Treatment 2 Interventions

Combination therapy of BNT326 and BNT327. In participants with second-line (or higher) 2L(+), squamous or non-squamous NSCLC, actionable genomic alterations (AGA)-negative/positive, any PD-L1.

Group XIV: Part 2b (Cohort D1, Arm 2) - Pembrolizumab Active Control 1 Intervention

Pembrolizumab monotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%.

Group XV: Part 2b (Cohort D2, Arm 2) - SoC - Pembrolizumab + chemotherapy Active Control 2 Interventions

Combination therapy of pembrolizumab and chemotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%.

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+

MediLink Therapeutics (Suzhou) Co., Ltd.

Industry Sponsor

Trials

12

Recruited

3,400+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3034

YL202/BNT326, a HER3-targeted ADC, in patients with ... We report preliminary safety and efficacy results from a phase I trial of YL202/BNT326. ... NSCLC: Efficacy and safety data from a phase 2 study.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07111520

Study Details | NCT07111520 | A Clinical Trial to Test if an ... This is a multi-site, open-label, dose-finding study, consisting of Parts 1, 2a, and 2b to investigate the combination of BNT326 with BNT327 in participants ...

3. clinicaltrials.biontech.com clinicaltrials.biontech.com/trials/BNT326-01

BNT326-01 This study will evaluate the safety, efficacy, optimal dose, and pharmacokinetics (PK) of BNT326 as monotherapy (Part 1) and as combination treatment with ...

4. withpower.com withpower.com/trial/phase-2-carcinoma-non-small-cell-lung-8-2025-26146

BNT326 + BNT327 for Lung Cancer Efficacy Follow-up. Participants are monitored for efficacy outcomes such as objective response rate and progression-free survival. up to 36 ...

5. mskcc.org mskcc.org/cancer-care/clinical-trials/25-247

A Phase 1-2 Study of BNT326 Alone or With BNT327 in ... The people in this study have cancers that have come back or keep growing after treatment, including: Melanoma of the skin. Non-small cell lung cancer. Bile ...

6. trial.medpath.com trial.medpath.com/clinical-trial/a5d7d9487c2e34c5/nct07111520-bnt326-bnt327-nsclc-trial

A Clinical Trial to Test if an Investigational Combination ... A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With ...