Trial results for a Phase 1/2 study (NCT04101357) investigating BNT411 as monotherapy and in combination with atezolizumab, carboplatin, and etoposide for solid tumors were posted on ClinicalTrials.gov on 2025-03-18. The trial was terminated and reported dose-limiting toxicities (DLTs) in 2 participants at the 7.2 mcg/kg BNT411 monotherapy dose and 2 participants at the 9.6 mcg/kg dose.
Background
The trial, titled "Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411," aimed to establish a safe dose of BNT411. BNT411 is described as a toll-like receptor 7 (TLR7) agonist, expected to induce broad innate and adaptive immune reactions, especially when combined with cytotoxic therapies and immune checkpoint inhibitors like atezolizumab. The study focused on participants with solid tumor and extensive-stage small cell lung cancer.
Trial design
The study (NCT04101357) was a Phase 1/2, first-in-human trial with an enrollment of 54 participants. It investigated BNT411 as a monotherapy and in combination with atezolizumab, carboplatin, and etoposide. The conditions studied were solid tumor and extensive-stage small cell lung cancer. The trial's overall status was TERMINATED.
Key results
The trial reported the number of participants with dose-limiting toxicities (DLTs) across various dose levels for BNT411 monotherapy and combination therapy.
- For BNT411 monotherapy, 0 participants experienced DLTs at doses ranging from 0.05 mcg/kg up to 6.0 mcg/kg.
- However, 2 participants experienced DLTs at the 7.2 mcg/kg monotherapy dose.
- Additionally, 2 participants experienced DLTs at the 9.6 mcg/kg monotherapy dose.
- In the combination therapy arms, 0 participants experienced DLTs at BNT411 doses of 1.2 mcg/kg and 2.4 mcg/kg when combined with atezolizumab, carboplatin, and etoposide.
The trial also reported on treatment-emergent adverse events (TEAEs). For the lowest monotherapy dose (0.05 mcg/kg), 2 participants experienced TEAEs, serious TEAEs, or Grade >=3 TEAEs.
What this means
The results indicate that higher monotherapy doses of BNT411 (7.2 mcg/kg and 9.6 mcg/kg) were associated with dose-limiting toxicities in this Phase 1/2 study. Lower monotherapy doses and the combination regimens with atezolizumab, carboplatin, and etoposide did not show DLTs within the tested ranges. The termination of the trial suggests that further development of BNT411, particularly at higher monotherapy doses, may have faced safety challenges, or other factors led to its discontinuation.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04101357, titled "Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411," were posted on 2025-03-18 on clinicaltrials.gov.