Boehringer Ingelheim has shared data on its DLL3xCD3 T-cell engager, providing pointers to the prospects of a would-be rival to Amgen’s Imdelltra that entered phase 3 this year.
Germany’s Boehringer arrived at the European Society for Medical Oncology Congress in Madrid with updated data from DAREON-9. The phase 1b small cell lung cancer trial is testing the tolerability of Boehringer’s bispecific, obrixtamig, in combination with the chemotherapy drug topotecan. An earlier cut of the data showed that 84% of patients had grade 3 or worse adverse events related to topotecan.
At ESMO, Boehringer allayed concerns that patients unable to receive a full dose of topotecan will have significantly worse outcomes. The company split the cohort of 60 second-line SCLC patients based on whether they received a relative dose intensity (RDI) of above or below 80%. RDI is the percentage of the planned chemotherapy dose that a patient actually received.
The confirmed overall response rate (ORR) was 72% in the RDI-low subpopulation, compared to 61% in RDI-high patients. Median progression-free survival (PFS) was the same—5.6 months—in both groups. Only the median duration of response favored the RDI-high group, with its 7.3 months numerically beating the 5.6 months of the RDI-low subgroup.
Amgen tested its DLL3xCD3 T-cell engager, Imdelltra, as a monotherapy in second-line and later SCLC. In its phase 2 DeLLphi-301 trial. The biotech linked Imdelltra to a 40% ORR and a median PFS of 4.9 months. Amgen’s phase 3 trial, DeLLphi-304, included a chemotherapy control arm that achieved a median PFS of 3.2 months.
Boehringer is targeting a different patient population in its phase 3 program. In April, investigators began enrolling first-line SCLC patients to receive obrixtamig in combination with a standard-of-care cocktail featuring Roche’s Tecentriq.
The study is one of two phase 3 obrixtamig trials that Boehringer has started this year. The other phase 3 trial, which began in July, is enrolling adults with advanced extrapulmonary neuroendocrine cancer (NEC). Participants are receiving obrixtamig in combination with a standard chemotherapy doublet.
Boehringer shared data on obrixtamig in DLL3-expressing NECs at ESMO. The drugmaker generated the data in the phase 1b DAREON-7 study. Boehringer reported a median PFS of 7.7 months in NEC patients who received obrixtamig plus standard-of-care platinum-based chemotherapy as a first-line treatment.
Median PFS was 9.5 months in a subgroup of patients with high DLL3 expression. The DLL3-low cohort had a median PFS of 7.6 months. The ORR in the DLL3-high and -low subgroups was 87.5% and 65.0%, respectively.
Amgen ran a phase 1 trial in neuroendocrine prostate cancer from 2021 to 2024. However, the biotech’s slate of active Imdelltra clinical trials focuses on SCLC. Ongoing clinical development in NECs is limited to investigator-initiated trials.