← Back to searchRecruitingRecruiting
A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer
NCT06892548 · BioNTech SE
In plain English
Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.
Official title
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
About this study
This is a two-part study designed to evaluate and establish two safe combination dose levels (recommended Phase 2 dose \[RP2D\] and a lower/another combination dose level \[RP2D-1\]) of BNT324 with BNT327 (Part 1), to determine the optimal combination dose (dose optimization \[DO\]) in NSCLC and SCLC lead indication cohorts at the RP2D and RP2D-1, to evaluate the preliminary efficacy in selected lung cancer cohorts at the highest combination dose level (in a signal seeking Part 2), and to confirm the clinical efficacy of BNT324 in combination with BNT327 at the optimal dose level in participants with advanced lung cancer in expansion cohorts (proof-of-concept \[POC\] cohorts).
The study consists of a screening period, a treatment period, a safety follow-up period, and a long-term survival follow-up period.
In Part 1 participants with histologically or cytologically confirmed relapsed or progressive lung cancer (both SCLC and NSCLC are eligible) will receive BNT324 in combination with BNT327 using a dose escalation design.
In Part 2 of the study, BNT324 will be studied in combination with BNT327 at the RP2D compared to RP2D-1 in participants with advanced metastatic treatment-naïve NSCLC (DO Cohort 1) and relapsed/progressive SCLC after failure of cytotoxic chemotherapy with or without immuno-oncology (IO) (DO Cohort 2). The totality of the available data (e.g., safety, efficacy, pharmacokinetics etc.) will be reviewed to select the optimal dose. After the optimal dose is selected, additional participants in each cohort may be enrolled in the selected optimal dose.
In the signal seeking cohorts (Cohort 3-7), participants will receive BNT324 in combination with BNT327 at the RP2D from Part 1.
A predefined number of participants in Part 2 Cohort 1 and Cohort 2 will be randomized to one of the two dose levels (RP2D and RP2D-1) selected from Part 1 in a 1:1 ratio. Additional participants in Part 2 Cohort 1 and Cohort 2 may be enrolled in the selected optimal dose to further assess the efficacy and safety profile.
No randomization is planned for any other cohort in Part 2 or Part 1.
Eligibility 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.
Study design
Enrollment target: 594 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-05-02
Estimated completion: 2031-06
Last updated: 2026-04-15
Interventions
Biological: BNT324Biological: BNT327
Primary outcomes
- • Part 1 - Occurrence of dose limiting toxicities (DLTs) by dose level (During the DLT evaluation period, i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days])
- • Part 1 - Occurrence of Treatment-emergent adverse events (TEAEs), serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs by dose level (From the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first)
- • Part 1 - Occurrence of dose interruption, reduction, and treatment discontinuations due to TEAEs by dose level (From the time of the first dose of IMP to 90 days after the last dose of IMP or until new anticancer therapy is started, whichever occurs first)
Sponsor
BioNTech SE · industry
With: DualityBio Inc., Biotheus Inc.
Contacts & investigators
ContactBioNTech clinical trials patient information · contact · patients@biontech.de · +49 6131 9084
InvestigatorBioNTech Responsible Person · study_director, BioNTech SE
All locations (58)
Mayo Clinic ArizonaRecruiting
Phoenix, Arizona, United States
Precision NextGen Oncology and Research CenterRecruiting
Beverly Hills, California, United States
Cedars Sinai Medical CenterRecruiting
Los Angeles, California, United States
UCLA - David Geffen School of MedicineRecruiting
Santa Monica, California, United States
Mayo Clinic in FloridaRecruiting
Jacksonville, Florida, United States
University of Iowa Hospitals & Clinics PARENTRecruiting
Iowa City, Iowa, United States
Mayo Clinic-RochesterRecruiting
Rochester, Minnesota, United States
John Theurer Cancer Center at Hackensack UMCRecruiting
Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center (MSKCC)Recruiting
New York, New York, United States
Icahn School of Medicine at Mount Sinai PRIMERecruiting
New York, New York, United States
Cleveland Clinic Taussig Cancer Institute Case Comprehensive Cancer CenterRecruiting
Cleveland, Ohio, United States
Texas Oncology - DFWRecruiting
Dallas, Texas, United States
MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
Texas Oncology - NortheastRecruiting
Tyler, Texas, United States
Virginia Cancer SpecialistsRecruiting
Fairfax, Virginia, United States
Chris O'Brien LifehouseRecruiting
Camperdown, New South Wales, Australia
Bendigo HospitalRecruiting
Bendigo, Victoria, Australia
Barwon HealthRecruiting
Geelong, Victoria, Australia
Sunshine HospitalRecruiting
Saint Albans, Victoria, Australia
St John of God Subiaco HospitalRecruiting
Subiaco, Western Australia, Australia
Beijing Cancer HospitalRecruiting
Beijing, Beijing Municipality, China
Beijing GoBroad HospitalRecruiting
Beijing, Beijing Municipality, China
Fujian Medical University Union HospitalRecruiting
Fuzhou, Fujian, China
Guangxi Medical University Cancer HospitalRecruiting
Nanning, Guangxi Zhuang, China
The First Affiliated Hospital of Xinxiang Medical UniversityRecruiting
Weihui, Henan, China
Henan Provincial Cancer HospitalRecruiting
Zhengzhou, Henan, China
Jingzhou First People's HospitalRecruiting
Jingzhou, Hubei, China
Xiangyang Central HospitalRecruiting
Xiangyang, Hubei, China
Yichang Central People's HospitalRecruiting
Yichang, Hubei, China
Nanjing Chest HospitalRecruiting
Nanjing, Jiangsu, China
The Second Affiliated Hospital of Nanchang UniversityRecruiting
Nanchang, Jiangxi, China
The First Affiliated Hospital of Nanchang UniversityRecruiting
Nanchang, Jiangxi, China
Jilin Cancer HospitalRecruiting
Changchun, Jilin, China
Linyi Cancer HospitalRecruiting
Shandong, Linyi, China
The First Affiliated Hospital of Xian Jiaotong UniversityRecruiting
Xi'an, Shaanxi, China
Jinan Central HospitalRecruiting
Jinan, Shandong, China
Shandong Cancer HospitalRecruiting
Jinan, Shandong, China
Shanghai GoBroad Cancer HospitalRecruiting
Shanghai, Shanghai Municipality, China
West China Hospital, Sichuan UniversityRecruiting
Chengdu, Sichuan, China
First Affiliated Hospital, Zhejiang University School of MedicineRecruiting
Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital, Zhejiang University, School of MedicineRecruiting
Hangzhou, Zhejiang, China
Zhejiang Cancer HospitalRecruiting
Hangzhou, Zhejiang, China
Kaohsiung Medical University Chung-Ho Memorial HospitalRecruiting
Kaohsiung City, Taiwan
Taichung Veterans General HospitalRecruiting
Taichung, Taiwan
National Cheng Kung University HospitalRecruiting
Tainan, Taiwan
Taipei Veterans General HospitalRecruiting
Taipei, Taiwan
Adana City HospitalRecruiting
Adana, Turkey (Türkiye)
Hacettepe University Medical FacultyRecruiting
Ankara, Turkey (Türkiye)
Dr. Abdurrahman Yurtaslan Oncology Teaching and Research HospitalRecruiting
Ankara, Turkey (Türkiye)
Ankara City HospitalRecruiting
Ankara, Turkey (Türkiye)
Yeditepe University Medical School HospitalRecruiting
Istanbul, Turkey (Türkiye)
Koc University HospitalRecruiting
Istanbul, Turkey (Türkiye)
Sakarya Training and Research HospitalRecruiting
Sakarya, Turkey (Türkiye)
Bristol Haematology and Oncology CentreRecruiting
Bristol, United Kingdom
St. James's University HospitalRecruiting
Leeds, United Kingdom
St George's Hospitals NHS Foundation TrustRecruiting
London, United Kingdom
University College London HospitalRecruiting
London, United Kingdom
The Christie NHS Foundation TrustRecruiting
Manchester, United Kingdom