A Study to Test Different Doses of Obrixtamig in Patients With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3

Official title

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

Overview

This study is open to adults with small cell lung cancer and other neuroendocrine cancers 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 and the best treatment schedule that people can tolerate. Obrixtamig is an antibody-like molecule (DLL3/CD3 bispecific) that may help the immune system fight cancer. In this study, obrixtamig is given to people for the first time. Interim clinical data are available for obrixtamig. Participants get obrixtamig either weekly or once every 3 weeks. 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 20 times depending on the response to the treatment. Doctors record any unwanted effects and regularly check the general health of the participants.

Interventions

• Drug Obrixtamig - parenteral 1
  Obrixtamig - parenteral 1
• Drug Obrixtamig - parenteral 2
  Obrixtamig - parenteral 2

Primary outcome measures

• Arm 1 and Arm 2: Maximum tolerated dose (MTD) [Time frame: up to 36 months]
• Arm 1 and Arm 2: Number of patients with DLTs in the MTD evaluation period [Time frame: up to 36 months]

Secondary outcome measures (3)

• Arm 1 and Arm 2: Maximum measured concentration (Cmax) of obrixtamig [Time frame: up to 36 months]
• Arm 1 and Arm 2: Area under the concentration-time curve (AUCτ) of the analyte over a uniform dosing interval τ [Time frame: up to 36 months]
• Arm 1 and Arm 2: Objective response based on RECIST 1.1 criteria in patients with measurable disease [Time frame: up to 36 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• Winship Cancer Institute — Atlanta
• University of Maryland School of Medicine — Baltimore
• Washington University School of Medicine — St Louis
• University of Pittsburgh Medical Center — Pittsburgh

Spain · 4 centers

• Hospital del Mar — Barcelona
• Hospital Universitari Vall d'Hebron — Barcelona
• Clínica Universidad de Navarra — Pamplona
• Hospital Clinico Universitario de Valencia — Valencia

Germany · 3 centers

• Universitätsklinikum Köln (AöR) — Cologne
• Technische Universität Dresden — Dresden
• Universitätsklinikum Würzburg AÖR — Würzburg

Japan · 1 center

• National Cancer Center Hospital East — Chiba, Kashiwa

Publications

• Wermke M, Felip E, Gambardella V, Kuboki Y, Morgensztern D, Hamed ZO, Liu M, Studeny M, Owonikoko TK. Phase I trial of the DLL3/CD3 bispecific T-cell engager BI 764532 in DLL3-positive small-cell lung cancer and neuroendocrine carcinomas. Future Oncol. 2022 Aug;18(24):2639-2649. doi: 10.2217/fon-2022-0196. Epub 2022 Jul 11. PMID 35815644

Identifiers

NCT: NCT04429087 · 1438-0001 · 2019-000729-31 · 2024-513100-34-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗