obrixtamig (BI 764532) / Boehringer Ingelheim, Oxford BioTherap - LARVOL DELTA

Obrixtamig (BI 764532) in patients (pts) with relapsed/refractory delta-like ligand 3 (DLL3)-high expressing extrapulmonary neuroendocrine carcinoma (epNEC): Dose expansion part of the phase II DAREON-5 trial. (ASCO-GI 2026) - P2 | "Funded by Boehringer Ingelheim Clinical Trial Registration Number: NCT05882058 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • P2 data • Gastrointestinal Cancer • Oncology • Solid Tumor • DLL3

DareonTM: DAREON™-5: A Study to Test Whether Different Doses of BI 764532 Help People With Small Cell Lung Cancer or Other Neuroendocrine Cancers (clinicaltrials.gov) - P2 | N=174 | Recruiting | Sponsor: Boehringer Ingelheim | Trial primary completion date: Oct 2026 ➔ Jan 2027

Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Oncology • Small Cell Lung Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma

DAREON™-7: A Study to Test How Well Different Doses of BI 764532 in Addition to Chemotherapy Are Tolerated by People With Advanced Neuroendocrine Cancers (clinicaltrials.gov) - P1 | N=55 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Aug 2026 ➔ Apr 2027 | Trial primary completion date: Jul 2026 ➔ Feb 2027

Trial completion date • Trial primary completion date • Endocrine Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor

A Study to Test How Well Different Doses of BI 764532 Are Tolerated by People With a Tumour in the Brain That is Positive for DLL3 (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Brain Cancer • Glioma • Oncology • Solid Tumor • DLL3

DAREON®-8: A phase I trial of first-line obrixtamig plus chemotherapy and atezolizumab in extensive-stage small cell lung carcinoma (ES-SCLC) (ESMO 2025) - P1 | "We report the first safety and efficacy data for the dose escalation part of the Phase I DAREON®-8 (NCT06077500) trial investigating obrixtamig + first-line (1L) SoC (carboplatin + etoposide + atezolizumab) in patients (pts) with ES-SCLC. The frequency and severity of AEs reported for the combination were consistent with the expected safety findings of the individual treatments. The combinability of obrixtamig with chemotherapy and an anti-PDL1 antibody observed in this trial warrant further development of this combination in 1L ES-SCLC."

Clinical • P1 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

A Study to Test How Well Different Doses of Obrixtamig (BI 764532) in Combination With Ezabenlimab Are Tolerated by People With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3 (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Phase classification: P1/2 ➔ P1 | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2025

Phase classification • Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

DAREON®-7: Phase I open-label dose-escalation/-expansion study of first-line obrixtamig (BI 764532) plus chemotherapy in patients with DLL3-positive neuroendocrine carcinomas (NANETS 2025) - P1 | "We report initial safety and efficacy data from the dose escalation part of the Phase I DAREON®-7 (NCT06132113) trial assessing obrixtamig plus simultaneous chemotherapy (carboplatin plus etoposide) in patients with DLL3-positive NECs. The reported frequency/ severity of AEs was consistent with the expected safety profile of the individual treatments, with no additional toxicities. Preliminary efficacy results were encouraging, warranting further development of the combination in this setting."

Clinical • P1 data • Endocrine Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor • DLL3

DAREON®-9: A phase Ib open-label dose escalation and dose confirmation study of obrixtamig (BI 764532) plus topotecan in patients (pts) with advanced small-cell lung cancer (SCLC): Updated results (ESMO 2025) - P1 | "Conclusions Obrixtamig + topotecan was tolerable with no indicators of overlapping toxicity. Preliminary efficacy data for the combination show encouraging short- and long-term efficacy in 2L+ SCLC, warranting further investigation of the combination treatment."

Clinical • Metastases • P1 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

DAREON-9, a phase Ib study of obrixtamig plus topotecan in patients (pts) with advanced small-cell lung cancer (SCLC): Interim analysis results (JADPRO 2025) - P, P1 | "In the 13 patients with $ge 2$ post-baseline tumor assessments (follow-up $ge 13$ weeks), the confirmed ORR was 69% (95% CI: 39–91). Median DOR was not reached."

Clinical • Metastases • P1 data • Lung Cancer • Mood Disorders • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

Obrixtamig (BI 764532) in patients (pts) with relapsed/refractory delta-like ligand 3 (DLL3)-high expressing extrapulmonary neuroendocrine carcinoma (epNEC): Trial in progress of the dose expansion part of the phase II DAREON®-5 trial (ESMO 2025) - P1, P2 | "Secondary endpoints include duration of objective response, PFS, disease control, overall survival, treatment-emergent AEs, and patient-reported outcomes. The planned enrollment for the expansion cohort is ∼50 pts recruited from the following countries: Belgium, China, Germany, Japan, Portugal, South Korea, Spain, UK and USA."

Clinical • P2 data • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor • DLL3

A Study to Test How BI 764532 is Taken up by Tumours in People With Small-cell Lung Cancer or Neuroendocrine Cancer (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Jul 2026 ➔ Nov 2026 | Trial primary completion date: Jan 2026 ➔ May 2026

Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Efficacy and safety of the DLL3/CD3 T-cell engager obrixtamig in patients with extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression: results from an ongoing phase I trial (JADPRO 2025) - P1 | "Dose 82n treated with Regimens B2 and B3 are reported here Dose 82.3 Dose 83.7 Dose B2.2 Dose B3 Dose 82.1 Key inclusion criteria Acvenced ЭСС, ерМЕС, epNEC Positive Patients with epNEC Patient screening and disposition by DLL3 status • All patients were required to have DLL3-positive tumors (>0% of TC with moderate-to-strong staining with an investigational antibody for DLL3 [SP347; Roche Diagnostics]} .DLL3 testing was performed at the Roche CDX CAP/CLIA Laboratory (Tucson) ⚫Tumors were categorized as either DLL3 (250% TC) or DLL3 (0% TO 0% TO' 260% TC' <60% TC* and dri 'OLLS-vedere as % Twining DL W. Bayi Logisto Regression Nose; D.LS, de a heigard 5 DLTS, dose limiting to cites appulmonary neuroend MTD, very to Crie in Goid Tumor mar 1.1 LONEC QOW werk RECIST v1.1 Response SOU, amellal lung cancer cel "TC gode ale and songs OLLS cela eigand SpYCC, expuray receiver TC ul. Patients Patient baseline characteristics and treatment exposure •..."

Clinical • P1 data • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor • DLL3

Obrixtamig (BI 764532) in relapsed/refractory delta-like ligand 3 (DLL3)-high extrapulmonary neuroendocrine carcinoma: Phase II DAREON®-5 dose-expansion trial in progress (NANETS 2025) - P1, P2 | "The planned enrollment for the expansion cohort is ~50 patients recruited from the following countries: Belgium, China, Germany, Japan, South Korea, Spain, UK, and USA. RESULTS N/A CONCLUSIONS N/A"

P2 data • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

An ongoing Phase 1 Trial of Obrixtamig in patients with Extrapulmonary Neuroendocrine Carcinomas with high or low DLL3 Expression (NANETS 2025) - P1 | "The safety profile was manageable and comparable across both groups. The ORR of 40.0% and median DoR of 7.9 months in heavily pretreated epNEC tumors with high DLL3 expression are encouraging and support further development of obrixtamig for this subgroup."

Clinical • P1 data • Endocrine Cancer • Neuroendocrine Carcinoma • Oncology • Solid Tumor • DLL3 • RB1

A Study to Test Different Doses of BI 764532 in Patients With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3 (clinicaltrials.gov) - P1 | N=300 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Dec 2025 ➔ Feb 2027 | Trial primary completion date: Sep 2025 ➔ Aug 2026

First-in-human • Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

DAREON-8: DAREONᵀᴹ-8: A Study to Test How Well Different Doses of BI 764532 in Addition to Standard of Care Are Tolerated by People With Advanced Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=46 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Study to Test How Well Different Doses of Obrixtamig (BI 764532) in Combination With Ezabenlimab Are Tolerated by People With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3 (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Sep 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

Phase I Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-Like T-Cell Engager Obrixtamig (BI 764532) in Patients With Delta-Like Ligand 3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas. (PubMed, J Clin Oncol) - "The demonstrated tolerability and efficacy of obrixtamig regimens, administered as step-up followed by target doses of 90-1,080 μg/kg (once weekly or once every 3 weeks), in patients with heavily pretreated DLL3-positive tumors support further exploration in SCLC, epNEC, and LCNEC-L."

Journal • P1 data • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

DAREON-8: DAREONᵀᴹ-8: A Study to Test How Well Different Doses of BI 764532 in Addition to Standard of Care Are Tolerated by People With Advanced Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=47 | Recruiting | Sponsor: Boehringer Ingelheim | Trial primary completion date: Aug 2025 ➔ Dec 2025

Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Five Under 5: Top Oncology Videos for the Week of 6/15 (OncLive) - "Jason S. Starr, DO...discusses the potential of delta-like ligand 3 as a therapeutic target in extrapulmonary neuroendocrine carcinomas (epNECs). DLL3, known for its high expression in small cell lung cancer, is similarly overexpressed in approximately 80% of epNEC cases, prompting evaluation of DLL3-directed therapies in this setting. During the 2025 ASCO Annual Meeting, Starr presented phase 1 NCT04429087) data showing that the DLL3/CD3 bispecific T-cell engager obrixtamig (BI 764532) yielded an ORR of 40% with a disease control rate (DCR) of 67% in DLL3-high epNECs, compared with an ORR of 3% and DCR of 27% in DLL3-low tumors. Starr noted that these findings, along with the agent's FDA fast track designation in October 2023, support ongoing investigation in the phase 2 DAREON-5 trial (NCT05882058)."

Audio

Dr Wermke on the Efficacy and Safety of Obrixtamig With Topotecan in Advanced SCLC (OncLive) - P1 | N=90 | DAREON-9 (NCT05990738) | Sponsor: Boehringer Ingelheim | "Martin Wermke...highlighted the clinical potential of obrixtamig, a DLL3/CD3-directed bispecific T-cell engager, in combination with topotecan for the treatment of patients with advanced small cell lung cancer (SCLC), based on early-phase data from the ongoing phase 1 DAREON-9 trial (NCT05990738)....Interim results showed an encouraging overall response rate (ORR) of 70% (95% CI, 47%-87%), with responses maintained at 69% (95% CI, 39%-91%) among the 13 patients who underwent confirmatory imaging....Topotecan-associated cytopenias were reported, including neutropenia (68%) and thrombocytopenia (92%), though no associated infectious or bleeding complications occurred. Obrixtamig-related cytokine release syndrome (CRS) occurred in 48% of patients; these were mostly grade 1 effects (44%), with a few grade 2 cases (4%). No grade 3 or higher CRS was observed."

P1 data • Small Cell Lung Cancer

Efficacy and safety of the DLL3/CD3 T-cell engager obrixtamig in patients with extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression: Results from an ongoing phase I trial. (ASCO 2025) - P1 | "Analyses from this ongoing Ph I study show greater obrixtamig efficacy in patients with epNEC with high DLL3 expression compared with low DLL3 expression, with a manageable safety profile that is comparable across both groups. The ORR of 40.0% and median DoR of 7.9 months in heavily pretreated epNEC tumors with DLL3 high expression are encouraging, and support further development of obrixtamig for this subgroup. *Evaluated with a customised MedDRA query."

Clinical • P1 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • DLL3 • RB1

DAREONTM-9, a phase Ib study of obrixtamig plus topotecan in patients (pts) with advanced small cell lung cancer (SCLC): Interim analysis results. (ASCO 2025) - P1 | "The obrixtamig plus topotecan combination was tolerable with no unexpected toxicities. AE frequency and severity reported for the combination were consistent with the expected safety findings for obrixtamig and topotecan as monotherapy. Preliminary efficacy data for the combination are encouraging and indicate an improvement on top of topotecan monotherapy."

Clinical • Metastases • P1 data • Anemia • Fatigue • Febrile Neutropenia • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • DLL3

Exploring precision medicine through DLL3 targeted therapy, obrixtamig (PRNewswire) - P1 | N=282 | NCT04429087 | Sponsor: Boehringer Ingelheim | "New data will be presented from the ongoing, Phase I dose escalation study (NCT04429087) evaluating T-cell engager, obrixtamig, in previously treated patients with extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression (N=60)....The objective response rate was 40% (95% CI: 24.6-57.7) in patients with high DLL3 expression compared to 3.3% (95% CI: 0.6-16.7) in patients with low DLL3 expression. The median duration of response was 7.9 months (95% CI: 6.2-not calculable [NC]) in patients with high DLL3 expression compared to 2.8 months (95% CI: NC-NC) in patients with low DLL3 expression. The disease control rate was 66.7% (95% CI: 48.8-80.8) in patients with high DLL3 expression compared to 26.7% (95% CI: 14.2-44.4) in patients with low DLL3 expression."

P1 data • Neuroendocrine Tumor

A Study to Test How Well Different Doses of BI 764532 Are Tolerated by People With a Tumour in the Brain That is Positive for DLL3 (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Sep 2025 ➔ Mar 2026

Monotherapy • Trial completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • DLL3