Dr Jänne on BL-B01D1 in NSCLC and Other Solid Tumors

Pasi A. Jänne, MD, PhD, director, Lowe Center for Thoracic Oncology, director, Belfer Center for Applied Cancer Science, director, Chen-Huang Center for EGFR Mutant Lung Cancers, senior physician, Dana-Farber Cancer Institute; professor, medicine, Harvard Medical School, discusses findings from a first-in-human phase 1 trial (NCT05194982) investigating the EGFRxHER3 bispecific antibody-drug conjugate (ADC) BL-B01D1 in patients with advanced non–small cell lung cancer (NSCLC) and other advanced solid tumors.

This trial included dose-escalation and dose-expansion parts that investigated the agent at several dose levels and treatment schedules, and enrolled patients with locally advanced or metastatic NSCLC, nasopharyngeal carcinoma, head and neck squamous cell carcinoma (HNSCC), small cell lung cancer (SCLC), and other solid tumors, Jänne says.

At a median follow-up of 4.1 months, in the total study population, the overall response rate (ORR) was 45.3%. In the patients with EGFR-mutant NSCLC, the ORR was 63.2% vs 44.9% in those with EGFR wild-type disease. All patients with EGFR-mutant NSCLC had received a prior EGFR TKI, and all patients with EGFR wild-type disease had received prior platinum-based chemotherapy, with medians of 3 and 2 prior lines of therapy in the EGFR-mutant and EGFR wild-type arms, respectively. These are high response rates in patients who have progressed on standard-of-care therapies, and demonstrate promising clinical activity with BL-B01D1, Jänne emphasizes. In patients with nasopharyngeal carcinoma, HNSCC, and SCLC, the ORRs were 53.6%, 6.7%, and 14.3%, respectively.

Additionally, this trial showed that BL-B01D1 had activity in patients with EGFR-mutant NSCLC regardless of their tumors’ EGFR inhibitor resistance mechanisms, which confirms previous findings with monoclonal HER3-directed ADCs, Jänne notes. Since most EGFR-mutant cancers have both HER3 and EGFR expression, the bispecific antibody portion of this ADC targets the expression of both proteins and is effective because HER3 is not a resistance mechanism to EGFR kinase inhibitors such as osimertinib (Tagrisso), Jänne explains. This phase 1 trial delivers a proof of concept that BL-B01D1 is effective in NSCLC tumors with resistance mechanisms to prior EGFR kinase inhibitors, Jänne concludes.