Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as YL202, anti-HER3 antibody conjugated to topoisomerase I inhibitor
BNT326 · 3 trials · 4 indications
During the DLT evaluation period by dose level
Defined as the percentage of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response.
By cohort and by dose in (Part 1), and by cohort and combination treatment regimen (in Part 2).
By cohort and by dose in (Part 1), and by cohort and combination treatment regimen (in Part 2)
Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) based on the investigator's assessment (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) is observed as best overall response. By cohort and by dose in (Part 1), and by cohort and combination treatment regimen (in Part 2).
During the DLT observation period.
Evaluation of Cmax without and in combination with the CYP inhibitors (± itraconazole or ± paroxetine). Treatment comparison using geometric mean ratio of Cycle 3 as compared with Cycle 2 as a reference.
Evaluation of AUC over the last 17-day dosing interval without and in combination with the CYP inhibitors (± itraconazole or ± paroxetine). Treatment comparison using geometric mean ratio of Cycle 3 as compared with Cycle 2 as a reference.
| Arm | Type | Description |
|---|---|---|
| Part 1 - BNT326 (DL1) + pumitamig (DL1) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig, starting dose. In participants with second-line (or higher) 2L(+), squamous or non-squamous NSCLC, actionable genomic alterations (AGA)-negative/positive, any programmed death-ligand 1 (PD-L1). |
| Part 1 - BNT326 (DL2) + pumitamig (DL1) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 1 - BNT326 (DL3) + pumitamig (DL1) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 1 - BNT326 (DL1) + pumitamig (DL2) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 1 - BNT326 (DL2) + pumitamig (DL2) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 1 - BNT326 (DL3) + pumitamig (DL2) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 2a (Cohort A, Arm 1) - BNT326 (DL1) + pumitamig (DL1) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 2a (Cohort A, Arm 2) - BNT326 (DL2) + pumitamig (DL1) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 2a (Cohort A, Arm 3) - BNT326 (DL3) + pumitamig (DL1) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 2a (Cohort A, Arm 4) - BNT326 (DL1) + pumitamig (DL2) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 2a (Cohort A, Arm 5) - BNT326 (DL2) + pumitamig (DL2) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 2a (Cohort A, Arm 6) - BNT326 (DL3) + pumitamig (DL2) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. |
| Part 2a (Cohort B, Arm 1) - BNT326 (DL1) + pumitamig (DL1) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with first-line (1L) squamous or non-squamous NSCLC, AGA-negative, any PD-L1. |
| Part 2a (Cohort B, Arm 2) - BNT326 (DL2) + pumitamig (DL1) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 1L squamous or non-squamous NSCLC, AGA-negative, any PD-L1. |
| Part 2a (Cohort B, Arm 3) - BNT326 (DL3) + pumitamig (DL1) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 1L squamous or non-squamous NSCLC, AGA-negative, any PD-L1. |
| Part 2a (Cohort B, Arm 4) - BNT326 (DL1) + pumitamig (DL2) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 1L squamous or non-squamous NSCLC, AGA-negative, any PD-L1. |
| Part 2a (Cohort B, Arm 5) - BNT326 (DL2) + pumitamig (DL2) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 1L squamous or non-squamous NSCLC, AGA-negative, any PD-L1. |
| Part 2a (Cohort B, Arm 6) - BNT326 (DL3) + pumitamig (DL2) | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 1L squamous or non-squamous NSCLC, AGA-negative, any PD-L1. |
| Part 2b (Cohort C, Arm 1) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or epithelial growth factor receptor (EGFR) activating mutation, any PD-L1. DLs used will be determined by the IRC based on data generated from Part 1 and Part 2a. |
| Part 2b (Cohort C, Arm 2) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1. DLs used will be determined by the IRC based on data generated from Part 1 and Part 2a. |
| Part 2b (Cohort D1, Arm 1) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%. DLs used will be determined by the IRC based on data generated from Part 1 and Part 2a. |
| Part 2b (Cohort D1, Arm 2) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%. DLs used will be determined by the IRC based on data generated from Part 1 and Part 2a. |
| Part 2b (Cohort D1, Arm 3) - Pumitamig monotherapy | EXPERIMENTAL | Pumitamig monotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%. DL used will be determined by the IRC based on data generated from Part 1 and Part 2a. |
| Part 2b (Cohort D2, Arm 1) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%. DLs used will be determined by the IRC based on data generated from Part 1 and Part 2a. |
| Part 2b (Cohort D2, Arm 2) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 and pumitamig. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%. DLs used will be determined by the IRC based on data generated from Part 1 and Part 2a. |
| Part 1 (Cohort 1A) - BNT326 monotherapy | EXPERIMENTAL | BNT326 (DL1 or DL2 or DL3) in participants with cutaneous melanoma 2L+ |
| Part 1 (Cohort 1B) - BNT326 monotherapy | EXPERIMENTAL | BNT326 (DL1 or DL2) in participants with NSCLC 2L+ AGA-negative |
| Part 1 (Cohort 1C) - BNT326 monotherapy | EXPERIMENTAL | BNT326 (DL1 or DL2) in participants with NSCLC 2L+ EGFRm |
| Part 1 (Cohort 1D) - BNT326 monotherapy | EXPERIMENTAL | BNT326 (DL2 or DL3) in participants with rare melanoma 2L+ |
| Part 1 (Cohort 1E) - BNT326 monotherapy | EXPERIMENTAL | BNT326 (DL2) in participants with advanced solid tumors 2L+ |
| Part 1 (Cohort 1F, DDI) - BNT326 + itraconazole | EXPERIMENTAL | BNT326 (DL1 or DL2 or DL3) + itraconazole in participants with advanced solid tumors |
| Part 1 (Cohort 1F, DDI) - BNT326 + paroxetine | EXPERIMENTAL | BNT326 (DL1 or DL2 or DL3) + paroxetine in participants with advanced solid tumors |
| Part 1 (Cohort 1G) - BNT326 monotherapy | EXPERIMENTAL | BNT326 (DL2 or DL3) in participants with cervical cancer 2L+ |
| Part 2 (Cohort 2A dose escalation) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 (DL1 or DL2 or DL3) + pumitamig (DL1 or DL2) in participants with cutaneous melanoma 2L+. Optionally, combinations with lower doses of BNT326 and/or pumitamig may be explored. |
| Part 2 (Cohort 2A dose randomization/expansion) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 (DL1 or DL2 or DL3) + pumitamig (DL3 or DL4 or DL 5) in participants with cutaneous melanoma 2L+. Optionally, combinations with lower doses of BNT326 and/or pumitamig may be explored. |
| Part 2 (Cohort 2B dose escalation) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 (DL1 or DL2 or DL3) + pumitamig (DL1 or DL2) in participants with HER2-negative breast cancer (triple-negative breast cancer and hormone receptor-positive /HER2-negative breast cancer) 2L+/1L |
| Part 2 (Cohort 2B dose randomization/expansion) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 (DL1 or DL2 or DL3) + pumitamig (DL3 or DL4 or DL 5) in participants with HER2-negative breast cancer (triple-negative breast cancer and hormone receptor-positive /HER2-negative breast cancer) 2L+/1L |
| Part 2 (Cohort 2C) - Optional - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 + pumitamig in participants with cutaneous melanoma 1L+ |
| Part 2 (Cohort 2D1) - BNT326 monotherapy | EXPERIMENTAL | BNT326 (DL2) in participants with GC/GEJC 2L+ |
| Part 2 (Cohort 2D2) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 (DL2 or DL3) + pumitamig (DL1 or DL2) in participants with GC/GEJC 2L+ |
| Part 2 (Cohort 2E1) - BNT326 monotherapy | EXPERIMENTAL | BNT326 (DL2) in participants with colorectal cancer 2L+ |
| Part 2 (Cohort 2E2) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 (DL2 or DL3) + pumitamig (DL1 or DL2) in participants with colorectal cancer 2L+ |
| Part 2 (Cohort 2F) - BNT326 + pumitamig | EXPERIMENTAL | Combination therapy of BNT326 with pumitamig in participants with cervical cancer 2L+ (BNT326 DL2 with pumitamig DL1 or DL2 or BNT326 DL3 with pumitamig DL1 or DL2) |
| YL202 Dose escalation | EXPERIMENTAL | YL202 will be administrated intravenously (IV) per dose level in which the patients are assigned. |
| Name | Type | Description |
|---|---|---|
| BNT326 | DRUG | intravenous (IV) infusion |
| Pumitamig | DRUG | IV infusion |
| Itraconazole | DRUG | Oral administration |
| Paroxetine | DRUG | Oral administration |
| YL202 | DRUG | YL202 is provided as the lyophilized powder, 200 mg/vial. YL202 will be given intravenously once every 3 weeks (Q3W) as a cycle. The initial dose of YL202 will be infused IV into each patient for 90 ±10 minutes. If there is no infusion-related reaction after the initial dose, the second and subsequent doses of YL202 will be infused IV into each patient for 60 ±10 minutes. |
Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified): * Aged ≥18 years at the time of giving informed consent. Local laws will be followed if the age of consent is older. * Have measurable disease defined by RECIST v1.1. * Have Eastern Cooperative Oncolog...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 3 | PHASE2 | Pembrolizumab, Gardasil 9 |
| Incyte Corporation | INCY | 1 | PHASE2 | Retifanlimab |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115 |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | Aldesleukin |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
BNT326 is an investigational antibody-drug conjugate being developed by BioNTech SE for advanced solid tumors, including non-small cell lung cancer. It is designed to deliver a topoisomerase I inhibitor payload to tumor cells. BNT326 is currently in Phase 1 clinical development and is not approved for any indication.
BNT326 targets HER3, a protein expressed on certain tumor cells. The antibody portion binds HER3 and delivers a topoisomerase I inhibitor payload into the cell. This targeted approach aims to concentrate the cytotoxic agent in HER3-expressing tumors while limiting exposure to normal tissues.
BNT326 is being studied for the treatment of advanced solid tumors, including non-small cell lung cancer. It is an investigational therapy and has not been approved for any use. Clinical trials are evaluating BNT326 both as a single agent and in combination with other investigational treatments such as BNT327.
BNT326 is being developed by BioNTech SE, a biotechnology company traded on the Nasdaq under the ticker BNTX. BioNTech is the sponsor of the ongoing Phase 1 clinical trials evaluating BNT326 in advanced solid tumors and non-small cell lung cancer.
BNT326 is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA or any regulatory agency. The Phase 1 program includes trials in advanced solid tumors and non-small cell lung cancer, with enrollment ongoing.
BNT326 is being evaluated in three Phase 1 trials. NCT07111520 is testing BNT326 plus BNT327 in advanced non-small cell lung cancer. NCT07070232 is studying BNT326 alone or with BNT327 in advanced malignant tumors. NCT05653752, also known as the YL202 study, is active but not recruiting in lung and breast cancer.
Yes, BNT326 is also known as YL202. It is an anti-HER3 antibody conjugated to a topoisomerase I inhibitor. The alternative name YL202 appears in the NCT05653752 trial title, which evaluates the drug in locally advanced or metastatic non-small cell lung cancer and breast cancer.