A study to test whether different doses of BI 764532 help people with small cell lung cancer or other neuroendocrine cancers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Oct 2023 → ongoing

Decision date (initial)

2023-09-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-504247-13-00

WHO UTN

U1111-1292-4406

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

This trial will have three parts: a dose selection part (Part 1), an epNEC expansion cohorts (Parts 2) and an epNEC expansion cohort with reduced monitoring (Part 3).
Part 1, Dose selection part objectives
The primary objective of the dose selection part (Part 1) is to evaluate safety and efficacy of two dose levels of BI 764532 monotherapy in patients with SCLC who have had progression or recurrence following after at least two prior lines of therapy, including at least one platinum-based regimen, and in patients with histologically or cytologically confirmed advanced or metastatic epNEC (excluding MCC, MTC and NEPC) or LCNEC of the lung as defined by the 2022 WHO classification of Neuroendocrine Neoplasms who have had progression or recurrence following at least one platinum-based regimen.
Part 2, epNEC Expansion cohort objectives
The epNEC expansion cohort will assess the efficacy and safety of BI 764532 monotherapy in patients with histologically or cytologically confirmed advanced or metastatic epNEC, and DLL3 high expression who have progression or recurrence following at least one platinum-based regimen.
The primary objective is to assess the anti-tumour activity of BI 764532 at the selected dose in DLL3 high expression epNEC patients where the primary measure of interest is the proportion of patients with objective response according to RECIST v 1.1 as assessed by blinded independent central review. Intercurrent event handling for the primary analysis of OR will be using a combined while-on-treatment and treatment policy strategy.
Part 3, epNEC Expansion cohort, reduced monitoring, objectives
The epNEC expansion cohort in Part 3 will assess the safety and efficacy of BI 764532 monotherapy at the selected dose with outpatient monitoring setting in patients with histologically or cytologically confirmed advanced or metastatic epNEC, and DLL3 high expression who have progression or recurrence following at least one platinum-based regimen.
The primary objective of Part 3 is to evaluate the safety (by incidence of treatment-emergent adverse events) and the efficacy (by proportion of patients with objective response (OR) by blinded independent central review) of BI 764532 at the selected dose with outpatient monitoring setting in DLL3 high expressing tumours.

Secondary objectives 1

1. Part 1, Dose selection part objectives The secondary objective is to further evaluate the efficacy of BI 764532 monotherapy by assessing duration of objective response (DOR), disease control (DC), progression-free survival (PFS) by investigator assessment, and overall survival (OS); explore the effect of BI 764532 on core patient-reported outcomes (PROs); further assess the safety and tolerability of BI 764532 monotherapy. Part 2, epNEC Expansion cohort objectives The secondary objectives are to estimate median duration of response by blinded independent central review, proportion of patients with disease control by blinded independent central review, median progression-free survival (PFS) by blinded independent central review and median overall survival (OS). Additional secondary objectives are to evaluate tolerability and safety (by incidence of treatment-emergent adverse events) and the assessment of patient-reported outcomes. Part 3, epNEC Expansion cohort, reduced monitoring, objectives The secondary objective of Part 3 is to estimate median duration of response (DoR) by blinded independent central review, proportion of patients with disease control by blinded independent central review, median progression-free survival (PFS) by blinded independent central review and median overall survival (OS), and to assess patient-reported outcomes. Additional secondary objectives are to evaluate tolerability and safety of BI 764532 (by occurrence of treatment-emergent adverse events (TEAEs) leading to study drug discontinuation during the on-treatment period).

Conditions and MedDRA coding

Large cell neuroendocrine carcinoma

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Researchers can request access to the documents regarding this study using the link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing, 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 on the website. Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program. Access Criteria: For study documents – upon signing of a ‚Document Sharing Agreement‘. For study data – 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male or female participants ≥18 years old and at least at the legal age of consent in countries where it is greater than 18 years at the time of signature of the informed consent form (ICF).
2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
3. Part 1: Histologically or cytologically confirmed, cancer of the following histologies: a. SCLC b. epNEC (except MCC, MTC and NEPC) c. LCNEC of the lung Patients with tumours with mixed histologies for any above type are eligible only if the neuroendocrine carcinoma/small tumour cells component is predominant and represents at least 50% of the overall tumour tissue. Patients must have progressed or recurred after standard of care therapy a. SCLC: after at least two prior lines of therapy, including at least one platinum-based regimen b. Therapy includes PD-L1 inhibitor treatment; patients should have received the combination of platinum-based regimen plus PD-L1 inhibitor unless they have been unable to receive checkpoint inhibitor treatment. c. epNEC/LCNEC: after at least one platinum-based regimen. Part 2 and part 3: Histologically or cytologically confirmed epNEC (except MCC, MTC and NEPC) with centrally assessed DLL3 high expression status. Patients must have progressed or recurred after at least one platinum-based regimen.
4. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
5. Measurable lesions as defined per RECIST v 1.1 within 21 days prior to the first dose of BI 764532.
6. Part 1: Availability of archival tumour tissue sample Part 2 and part 3: Availability of archival formalin-fixed paraffin-embedded (FFPE) tumour tissue sample. Following specimens are not allowed: Fine Needle Aspiration (FNA), Cytology samples, decalcified bone samples.
7. Adequate organ function as defined in the protocol.
8. All toxicities related to previous anti-cancer therapies have resolved ≤ CTCAE Grade 1 prior to trial treatment administration (except for alopecia, peripheral neuropathy , fatigue and endocrinopathies controlled by replacement therapy which must be ≤ CTCAE Grade 2 and amenorrhea/menstrual disorders which can be any grade).
9. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria and instructions on the duration of their use is provided in the participant information and in the protocol.
10. Only for Part 3, at the timepoint of Screening 02: - For Cycle 1, patients should be willing to stay within 1 hour driving distance for 48 hours after IMP administration and confirm availability of a caregiver for the same timeframe. - Patients should be considered suitable by the investigator to follow instructions applicable to the reduced monitoring cohort, such as taking their temperature and administration of oral medication at home if needed.

Exclusion criteria 9

1. 1. Untreated or symptomatic brain metastases (Part 2 and part 3: identified during the mandatory assessment by brain MRI within 21 days before first trial drug administration.) Participants with treated, stable 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 BI 764532. - 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 CNS disease
2. 7. Diagnosis of immunodeficiency or systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of BI 764532. Physiological replacement of steroids is allowed.
3. 8. Unresolved toxicity from prior anti-tumour therapy, defined in the inclusion criteria.
4. 9. Further exclusion criteria apply.
5. 2. Presence of leptomeningeal disease or, part 2 and part 3: epidural disease including spinal cord compression.
6. 3. Part 1: Active/previous history of interstitial lung disease or non-infectious pneumonitis (any grade). Part 2: Active/previous history of interstitial lung disease, pulmonary fibrosis, organizing pneumonia or non-infectious pneumonitis (any grade). Patients with a history of therapy-related pneumonitis that is considered clinically resolved are eligible.
7. 4. Participants who experienced severe, life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents.
8. 5. Prior anti-cancer therapy: • Patients who have been treated with any other anti-cancer drug within 4 weeks or within 5 half-life periods (whichever is shorter) prior to first administration of BI 764532. • Patients who have been treated with extensive field radiotherapy including whole brain irradiation within 2 weeks prior to first administration of BI 764532.
9. 6. Previous treatment with DLL3-targeting T cell engagers or cell therapies.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Part 1: Objective response (OR), defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v 1.1 by investigator assessment from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent.
2. Part 1: Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period.
3. Part 2: Objective response (OR), defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v 1.1 by blinded independent central review from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent.
4. Part 3: Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period.
5. Objective response (OR) by blinded independent central review.

Secondary endpoints 10

1. Part 1: Duration of objective response (DOR) based on investigator assessment. DOR is defined as the time from first documented confirmed OR until the earliest date of disease progression or death among patients with confirmed OR.
2. Part 1: Progression-free survival (PFS) based on investigator assessment. PFS is defined as the time from treatment start until the earliest date of tumour progression according RECIST v 1.1 or death from any cause, whichever occurs first.
3. Part 1: Disease control (DC), defined as best overall response of CR or PR or stable disease (SD) based on investigator assessment, where best overall response is defined according to RECIST v 1.1, from first treatment administration until the earliest of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent.
4. Part 1, 2, and 3: Overall survival (OS), defined as the time from treatment start until death from any cause.
5. Part 1, 2 y 3: The following endpoints reflecting patient-reported outcomes (PRO) will be assessed with the following PRO measures: - Change from baseline in EORTC QLQ-C30 physical functioning domain score - Change from baseline in EORTC QLQ-C30 role functioning domain score
6. Part 1, 2, and 3: Occurrence of treatment-emergent AEs leading to study drug discontinuation during the on-treatment period.
7. Part 2 and 3: Duration of objective response (DOR) based on blinded independent central review.
8. Part 2 and 3: Progression-free survival (PFS) based on blinded independent central review.
9. Part 2 and 3: Disease control (DC) based on blinded independent central review.
10. Part 2: Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Locations

8 EU/EEA countries · 34 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 139 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications