Testing a new treatment for small cell lung cancer and neuroendocrine tumors

A First-In-human Phase I, Non-randomized, Open-label, Multi-center Dose Escalation Trial of Obrixtamig (BI 764532) Administered by Parenteral Route in Patients With Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3

This study is testing a new treatment called BI 764532 for adults with advanced small cell lung cancer and neuroendocrine tumors to see how well it works and how often it should be given.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Boehringer Ingelheim (industry)
• Drugs / interventions: Rovalpituzumab, chemotherapy
• Locations: 12 sites (Atlanta, Georgia and 11 other locations)
• Trial ID: NCT04429087 on ClinicalTrials.gov

What this trial studies

This study is designed for adults with advanced small cell lung cancer and other neuroendocrine tumors that express the DLL3 marker. It aims to determine the highest tolerable dose and optimal treatment schedule of BI 764532, a bispecific antibody that may enhance the immune response against cancer. Participants will receive the treatment either weekly or every three weeks for up to three years, with regular monitoring for side effects and treatment response. This is the first time BI 764532 is being administered to patients, making it a novel approach in this setting.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced small cell lung carcinoma or other neuroendocrine tumors that are DLL3 positive.

Not a fit: Patients with tumors that do not express DLL3 or those with curable cancer are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with limited treatment alternatives.

How similar studies have performed: While this specific approach is novel, similar immunotherapy strategies have shown promise in treating other cancers.

Eligibility criteria

Inclusion Criteria:

* Signed and dated, written informed consent form (ICF2, ICF3 or ICF4) in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) - Good Clinical Practice (GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses.
* Locally advanced or metastatic cancer not amenable to curative treatment; of 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 DLL3 expression (on archived tissue or instudy fresh biopsy) according to central pathology review in order to start obrixtamig
  * Patients with tumours 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 tumour tissue.
* For back-fill cohorts only: patient has agreed to and signed an IC to provide mandatory pre-treatment and on-treatment fresh tumor biopsy.
* Patient has failed or is not eligible for available standard therapies according to local guidelines. Standard therapies should include at least one line of chemotherapy that should include platinum for patients with small cells carcinoma tumors histologies.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* At least one evaluable lesion outside of CNS as defined per modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
* Subjects with brain metastases are eligible provided they meet the following criteria:

  * Radiotherapy or surgery for brain metastases was completed at least 2 weeks prior to the first administration of obrixtamig
  * Patient is off steroids for at least 7 days (physiologic doses of steroids are permitted), and the patient is off anti-epileptic drugs for at least 7 days or on stable doses of anti-epileptic drugs for malignant Central Nervous System (CNS) disease.
* Adequate liver, bone marrow and renal organ function. Further inclusion criteria apply.

Exclusion Criteria:

* Previous treatment with T cell Engager (TcE) or cell therapies targeting DLL3. Other DLL3 targeting agents (like Rovalpituzumab tesirine (RovaT)) are allowed only if DLL3 positivity is documented after completion of treatment with DLL3 targeting agent in post-treatment biopsy.
* Anticoagulant treatment that cannot be safely interrupted based on opinion of the investigator if medically needed (e.g. biopsy).
* Persistent toxicity from previous treatments that has not resolved to = Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (except for alopecia, CTCAE Grade 2 neuropathy, asthenia/fatigue or grade 2 endocrinopathies controlled by replacement therapy).
* Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of obrixtamig. Physiological replacement of steroids is allowed.
* Prior anti-cancer therapy:

  * Patients who have been treated with any other anti-cancer drug within 3 weeks or within 5 half-life periods (whichever is shorter) prior to first administration of obrixtamig.
  * Patients who have been treated with extensive field radiotherapy including whole brain irradiation within 2 weeks prior to first administration of obrixtamig.
* Other active malignancy that could interfere with the prognosis and treatment of the disease of the study.
* Major surgery within 28 days of first dose obrixtamig.
* Women who are pregnant (including those who are considered to be possibly pregnant based on the investigator's clinical judgement), nursing/breast feeding or who plan to become pregnant or nurse while in the trial or within 60 days after the last dose of study treatment.
* Presence of any infection requiring systemic antimicrobial treatment within 7 days prior to first dose of trial medication. Patients who have any clinical signs of infection within 48 h prior to first dose of trial medication are not eligible.

Further exclusion criteria apply.

Where this trial is running

Atlanta, Georgia and 11 other locations

• Winship Cancer Institute — Atlanta, Georgia, United States (RECRUITING)
• University of Maryland School of Medicine — Baltimore, Maryland, United States (RECRUITING)
• Washington University School of Medicine — St Louis, Missouri, United States (RECRUITING)
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States (COMPLETED)
• Universitätsklinikum Köln (AöR) — Cologne, Germany (COMPLETED)
• Technische Universität Dresden — Dresden, Germany (RECRUITING)
• Universitätsklinikum Würzburg AÖR — Würzburg, Germany (RECRUITING)
• National Cancer Center Hospital East — Chiba, Kashiwa, Japan (RECRUITING)
• Hospital del Mar — Barcelona, Spain (RECRUITING)
• Hospital Universitari Vall d'Hebron — Barcelona, Spain (RECRUITING)
• Clínica Universidad de Navarra — Pamplona, Spain (RECRUITING)
• Hospital Clinico Universitario de Valencia — Valencia, Spain (RECRUITING)

Study contacts

• Study coordinator: Boehringer Ingelheim

Conditions: Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3