A Phase I, Non-randomized, Open-label, Multi-center Dose Escalation Trial of Obrixtamig (BI 764532) Combined With Ezabenlimab in Patients With Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3
Overview
- Phase
- Phase 1
- Intervention
- Obrixtamig
- Conditions
- Small Cell Lung Carcinoma (SCLC)
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 45
- Locations
- 12
- Primary Endpoint
- Occurrence of Dose Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) evaluation period
- Status
- Active, not recruiting
- Last Updated
- 4 days ago
Overview
Brief Summary
This study is open to adults with small cell lung cancer and other neuroendocrine tumours that are positive for the tumour marker Delta-like 3 (DLL3). The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists.
The purpose of this study is to find out the highest dose of obrixtamig that people can tolerate when taken together with another medicine called ezabenlimab. Obrixtamig and ezabenlimab may help the immune system fight cancer. Participants get obrixtamig and ezabenlimab as infusions into a vein.
If there is benefit for the participants and if they can tolerate it, the treatment is given for a maximum of 3 years. During this time, participants visit the study site about every week. The visits also depend on the response to the treatment. At the study visits, the doctors check the health of the participants, take necessary laboratory tests, and note any health problems that could have been caused by the study treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years
- •Signed and dated, written informed consent form (main ICF) in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
- •Diagnosed with locally advanced, metastatic or relapsed cancer not amenable to curative treatment of the following histologies:
- •Small cell lung carcinoma (SCLC)
- •Large cells neuroendocrine lung carcinoma(LCNEC)
- •Neuroendocrine carcinoma (NEC) or small cell carcinoma of any other origin
- •Tumours must be positive for Delta-like 3 (DLL3) expression (on archived tissue) according to central pathology review in order to start obrixtamig.
- •Patients with tumors with mixed histologies for any above type are eligible only if neuroendocrine carcinoma/small tumor cells component is predominant and represent at least 50% of the overall tumor tissue.
- •Patient who failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Patient must have exhausted available treatment options known to prolong survival for their disease. Previous therapies should include at least one line of platinum-based chemotherapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
Exclusion Criteria
- •Previous treatment with T-cell-engager (TcE) or cell therapies targeting DLL
- •Other DLL3 targeting agents (like RovaT) are allowed only if DLL3 positivity is documented after completion of treatment with DLL3 targeting agent in post-treatment biopsy.
- •Previous or concomitant malignancies other than the one treated in this trial within the last 2 years except:
- •effectively treated non-melanoma skin cancers
- •effectively treated carcinoma in situ of the cervix
- •effectively treated ductal carcinoma in situ
- •other effectively treated malignancy that is considered cured by local treatment
- •Major injuries and/or surgery or bone fracture within 28 days of first dose obrixtamig, or planned surgical procedures
- •Known leptomeningeal disease or spinal cord compression due to metastatic disease
- •Anticoagulant treatment that cannot be safely interrupted based on opinion of the investigator if medically needed
Arms & Interventions
obrixtamig + ezabenlimab treatment group
Successive cohorts of patients will receive increasing doses of obrixtamig in combination with ezabenlimab until the maximum tolerated dose (MTD) is reached, or upon decision of Dose Escalation Committee (DEC).
Intervention: Obrixtamig
obrixtamig + ezabenlimab treatment group
Successive cohorts of patients will receive increasing doses of obrixtamig in combination with ezabenlimab until the maximum tolerated dose (MTD) is reached, or upon decision of Dose Escalation Committee (DEC).
Intervention: Ezabenlimab
Outcomes
Primary Outcomes
Occurrence of Dose Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) evaluation period
Time Frame: up to 19 months
Secondary Outcomes
- Occurrence of DLTs during the on-treatment period(up to 19 months)
- Objective response, defined as best overall response of complete response (CR) or partial response (PR)(up to 19 months)
- Cmax (maximum measured concentration of obrixtamig)(up to 19 months)
- Cmax (maximum measured concentration of ezabenlimab)(up to 19 months)
- AUCτ (area under the concentration-time curve of obrixtamig over a uniform dosing interval τ)(up to 19 months)
- AUCτ (area under the concentration-time curve of ezabenlimab) over a uniform dosing interval τ)(up to 19 months)