Home › Trials › NCT06892548

Investigating a new combination therapy for advanced lung cancer

A Phase Ib/II, Multi-site, Open-label, Two-part Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Recommended Combination Dose of BNT324 With BNT327 in Participants With Advanced Lung Cancer

Phase1; Phase2 Interventional BioNTech SE · NCT06892548

This study is testing a new combination treatment for advanced lung cancer to see if it’s safe and effective for patients.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment594 (estimated)
Ages18 Years and up
SexAll
SponsorBioNTech SE Industry-sponsored
Drugs / interventionsdatopotamab, trastuzumab, chemotherapy
Locations58 sites (Phoenix, Arizona and 57 other locations)
Trial IDNCT06892548 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the efficacy and safety of a combination therapy using BNT324, a B7-H3 antibody-drug conjugate, and BNT327, a bispecific antibody targeting PD-L1 and VEGF, in patients with advanced lung cancer. The study is divided into two parts: the first part focuses on establishing safe dosage levels through a dose escalation design, while the second part aims to confirm the clinical efficacy of the optimal dose in specific lung cancer cohorts. Participants will undergo a screening period, treatment, safety follow-up, and long-term survival follow-up.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically or cytologically confirmed advanced or metastatic lung cancer, specifically those with relapsed or progressive small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC).

Not a fit: Patients with early-stage lung cancer or those who have not received prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced lung cancer, potentially improving survival rates.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in lung cancer, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Aged ≥18 years at the time of giving informed consent.
* Histological or cytological confirmed unresectable advanced/metastatic lung cancer. Histological classification may be based on tumor samples prior to metastatic disease. Participants with mixed histology must be classified based on the main component. Participants with NSCLC are eligible with any or no PD-L1 expression. Participants with AGA-positive disease must have received targeted therapy prior to enrollment in this study.

  * Part 1: Participants with NSCLC and SCLC
  * Part 2 Cohort 1: Participants with NSCLC (subpopulation 1) AGA negative, 1L
  * Part 2 Cohort 2: Participants with SCLC, 2L+
  * Part 2 Cohort 3: Participants with NSCLC (subpopulation 1) AGA negative, 2L+
  * Part 2 Cohort 4: Participants with NSCLC (subpopulation 2) AGA negative, 1L
  * Part 2 Cohort 5: Participants with NSCLC (subpopulation 2) AGA negative, 2L+
  * Part 2 Cohort 6: Participants with NSCLC AGA positive
  * Part 2 Cohort 7: Participants with SCLC, 1L
* Have measurable disease defined by RECIST version 1.1.
* Have an Eastern Cooperative Oncology Group performance status of 0 or 1.
* Have a life expectancy of ≥12 weeks.

Exclusion Criteria:

* Prior treatment with B7-H3 targeted therapy.
* Prior treatment with ADC with topoisomerase inhibitor (e.g., datopotamab deruxtecan, trastuzumab deruxtecan). Note: This exclusion applies to participants in the first-line/treatment-naïve cohorts in the advanced/metastatic setting. Prior treatment with ADC with topoisomerase inhibitor payload is only allowed for participants in the second-line plus cohorts in the advanced/metastatic setting.
* Is a candidate to locoregional treatment (including surgical resection, stereotactic radiotherapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as "radical" intent), per investigator's assessment.
* Has a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator, e.g., Grade 4 febrile neutropenia or recurrent/persistent Grade 3 to 4 neutropenia.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply to all or some participants depending on the cohort.

Where this trial is running

Phoenix, Arizona and 57 other locations

+8 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Lung CancerSmall cell lung cancerNon-small cell lung cancerProgrammed death-ligand 1Vascular endothelial growth factorBispecific antibodyBNT324BNT327
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.