Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3Phase 1NCT04429087
A Study to Test Different Doses of Obrixtamig in Patients With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3
A Phase 1 study testing Obrixtamig - parenteral 1 and Obrixtamig - parenteral 2 in people with Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3, run by Boehringer Ingelheim at 12 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3
- What is being tested?
- Obrixtamig - parenteral 1 and Obrixtamig - parenteral 2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 306 participants
- Where
- 12 sitesin 4 countries
- Study dates
- 29 Jul 2020to 1 Oct 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
12 sites in 4 countries.
12 sites in 4 countries
United States4 sites
Winship Cancer Institute
Atlanta, Georgia, 30322
University of Maryland School of Medicine
Baltimore, Maryland, 21201
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
Washington University School of Medicine
St Louis, Missouri, 63108
Spain4 sites
Hospital del Mar
Barcelona, 08003
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Clínica Universidad de Navarra
Pamplona, 31008
Hospital Clinico Universitario de Valencia
Valencia, 46010
Germany3 sites
Universitätsklinikum Köln (AöR)
Cologne, 50937
Technische Universität Dresden
Dresden, 01307
Universitätsklinikum Würzburg AÖR
Würzburg, 97078
About this study
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
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.
- Being tested
- Obrixtamig - parenteral 1, Obrixtamig - parenteral 2
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Obrixtamig - parenteral 1Drug
Also called BI 764532
Obrixtamig - parenteral 1
Obrixtamig - parenteral 2Drug
Also called BI 764532
Obrixtamig - parenteral 2
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Obrixtamig | Experimental | Not described Receives: Drug: Obrixtamig - parenteral 1 |
| Arm 2: Obrixtamig | Experimental | Not described Receives: Drug: Obrixtamig - parenteral 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arm 1 and Arm 2: Maximum tolerated dose (MTD)
Maximum tolerated dose (MTD) in any studied regimen defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal or above 33% during the MTD evaluation period. Separate MTDs will be determined for each Regimen.
Measured: up to 36 months
Arm 1 and Arm 2: Number of patients with DLTs in the MTD evaluation period
Measured: up to 36 months
Secondary outcomes (3)
Arm 1 and Arm 2: Maximum measured concentration (Cmax) of obrixtamig
Measured: 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
Measured: up to 36 months
Arm 1 and Arm 2: Objective response based on RECIST 1.1 criteria in patients with measurable disease
Objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients with measurable disease
Measured: up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2020
- Study start29 Jul 2020
- Primary completion31 Aug 2026
- Study completion1 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3Studies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 306 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04429087
- Sponsor's protocol ID
- 1438-0001
- Other IDs
- 2019-000729-31, 2024-513100-34-00, 2019
- Status last verified
- Sep 2026
- First submitted
- 10 Jun 2020
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Once the criteria in section 'time frame' are fulfilled, researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
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.
PubMed 35815644
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04429087
- Acronym / sponsor ID
- 1438-0001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 306 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 29 Jul 2020 (actual)
- Primary completion
- 31 Aug 2026 (actual)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 12 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Obrixtamig | Experimental | Drug: Obrixtamig - parenteral 1 |
| Arm 2: Obrixtamig | Experimental | Drug: Obrixtamig - parenteral 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
- 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.
Key exclusion criteria (12 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Obrixtamig - parenteral 1Also: BI 764532Obrixtamig - parenteral 1 | Drug | Arm 1: Obrixtamig |
| Obrixtamig - parenteral 2Also: BI 764532Obrixtamig - parenteral 2 | Drug | Arm 2: Obrixtamig |
Primary outcome
Arm 1 and Arm 2: Maximum tolerated dose (MTD)
Time frame: up to 36 months
Maximum tolerated dose (MTD) in any studied regimen defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal or above 33% during the MTD evaluation period. Separate MTDs will be determined for each Regimen.
Arm 1 and Arm 2: Number of patients with DLTs in the MTD evaluation period
Time frame: up to 36 months
3 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Derived from this study: PubMed 35815644Wermke 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Once the criteria in section 'time frame' are fulfilled, researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Obrixtamig - parenteral 1 and Obrixtamig - parenteral 2 in people with Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3, run by Boehringer Ingelheim at 12 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Spain, Germany, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arm 1 and Arm 2: Maximum tolerated dose (MTD) (time frame: up to 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04429087, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.