A study to test whether BI 907828 helps people with cancer in the biliary tract, pancreas, lung, or bladder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH, Boehringer Ingelheim Espana S.A., Boehringer Ingelheim RCV GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Nov 2022 → 25 Sep 2025

Decision date (initial)

2023-11-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-506369-79-00

EudraCT number

2022-001500-18

WHO UTN

U1111-1292-3392

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

To assess the efficacy, safety, and tolerability of BI 907828 monotherapy in the following cohorts of patients:
Cohort 1: Biliary tract adenocarcinoma (cholangiocarcinoma, gallbladder cancer, and ampullary cancer)
Cohort 2: Pancreatic ductal adenocarcinoma
Cohort 3: Lung adenocarcinoma
Cohort 4: Urothelial bladder cancer

Conditions and MedDRA coding

Pancreatic ductal adenocarcinoma

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003260-PIP02-23

Plan to share IPD

Yes

IPD plan description

Researchers can use the following link https://www.mystudywindow.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 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 11

1. Diagnosis of a solid tumour which meets the criteria for an open trial cohort: o Cohort 1 (biliary tract adenocarcinoma): Locally advanced or metastatic biliary tract adenocarcinoma (intra- and extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary cancer). Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards; or (in the opinion of the investigator) patients are unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy. o Cohort 2 (pancreatic ductal adenocarcinoma): Locally advanced or metastatic pancreatic ductal adenocarcinoma. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards. o Cohort 3 (lung adenocarcinoma): Locally advanced or metastatic lung adenocarcinoma. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards. o Cohort 4 (urothelial bladder cancer): Locally advanced or metastatic urothelial bladder cancer. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
2. Written pathology report / molecular profiling report indicating MDM2 amplification or a copy number ≥8, and TP53 wild-type status. This must have been confirmed with a tissue-based test. A test with liquid biopsy is not accepted.
3. Archival tissue (formalin fixed paraffin embedded [FFPE] tumour blocks or slides) must be provided for retrospective confirmation of MDM2 amplification and TP53 status.
4. Presence of at least 1 measurable target lesion according to RECIST version 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
6. Patient must be willing to donate mandatory blood samples for the pharmacokinetics, pharmacodynamics, and biomarker analyses.
7. Adequate organ function, as specified in the protocol.
8. All toxicities related to previous anti-cancer therapies have resolved to ≤CTCAE Grade 1 prior to trial treatment administration (except for alopecia and amenorrhea / menstrual disorders which can be of any grade and peripheral neuropathy which must be ≤CTCAE Grade 2).
9. Life expectancy ≥3 months at the start of treatment in the opinion of the investigator.
10. Provision of signed and dated, written informed consent form (ICF) in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
11. Male or female patients ≥18 years old at the time of signature of the ICF. Women of childbearing potential and men able to father a child must be ready and able to use 2 medically 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 beginning at screening, during trial participation, and until 6 months and 12 days after last dose for women and 102 days after last dose for men. A list of contraception methods meeting these criteria is provided in the patient information.

Exclusion criteria 13

1. Previous administration of BI 907828 or any other MDM2-p53 or MDMX (MDM4)-p53 antagonist.
2. Active bleeding, significant risk of haemorrhage (e.g. previous severe gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current bleeding disorder (e.g. haemophilia, von Willebrand disease).
3. Major surgery (major according to the investigator’s assessment) performed within 4 weeks prior to start of trial treatment or planned within 6 months after screening (e.g. hip replacement).
4. Clinically significant previous or concomitant malignancies in the opinion of the investigator affecting the efficacy and/or outcome of the trial.
5. Patients who must or intend to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
6. Currently enrolled in another investigational device or drug trial.
7. Any history of, or concomitant condition that, in the opinion of the investigator, would compromise the patient’s ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the trial drug.
8. Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator’s opinion, makes the patient an unreliable trial participant).
9. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Female patients who do not agree to the interruption of breastfeeding from the start of trial treatment until 6 months and 12 days after last dose of trial treatment.
10. Patients with known history of human immunodeficiency virus (HIV) infection who meet 1 or more of the following criteria: o CD4+ count <350 cells/μL o Viral load >400 copies/mL (local laboratory assessment) o Not receiving antiretroviral therapy o Receiving established antiretroviral therapy for <4 weeks prior to the start of trial treatment o History of AIDS-defining opportunistic infections within 12 months prior to start of trial treatment Patients with a history of HIV who do not meet any of the criteria above are eligible to participate but the patient must be under the care of a HIV/Infectious Diseases specialist or a HIV/Infectious Diseases specialist must be consulted prior to inclusion.
11. Patients with a history of HCV infection who meet 1 or more of the following criteria: o Currently receiving curative antiviral treatment o Not yet achieved sustained viral response (SVR) o HCV viral load is above the limit of quantification (HCV RNA positive)
12. Patients with chronic HBV infection with active disease who meet the criteria for anti- HBV therapy (according to local / institutional standard) and who have not been treated with suppressive antiviral therapy prior to initiation of trial treatment.
13. Further exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response (OR) based on central independent review

Secondary endpoints 10

1. Duration of objective response (DOR) based on central independent review
2. Progression-free survival (PFS) based on central independent review
3. Overall survival (OS)
4. Disease control (DC) based on central independent review
5. Occurrence of treatment-emergent adverse events (AEs) during the on-treatment period.
6. Occurrence of treatment-emergent AEs leading to trial drug discontinuation during the on-treatment period.
7. Change from baseline in EORTC QLQ-C30 physical functioning domain score
8. Change from baseline in EORTC QLQ-C30 fatigue domain score
9. Change from baseline in EORTC QLQ-C30 role functioning domain score
10. Change from baseline in EORTC QLQ-BIL21 tiredness domain score

Investigational products

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

Test 3

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

Boehringer Ingelheim Espana S.A.

Sponsor organisation

Boehringer Ingelheim Espana S.A.

Address

Carrer Prat De La Riba 50, Sant Cugat Del Valles Sant Cugat Del Valles

City

Barcelona

Postcode

08174

Country

Spain

Boehringer Ingelheim RCV GmbH & Co. KG

Sponsor organisation

Boehringer Ingelheim RCV GmbH & Co. KG

Address

Dr.-Boehringer-Gasse 5-11, Meidling Meidling

City

Vienna

Postcode

1121

Country

Austria

Sponsor responsibilities

Article 77 compliance

Boehringer Ingelheim International GmbH

Contact point sponsor

Boehringer Ingelheim International GmbH

Article 77 implementation

Boehringer Ingelheim International GmbH

Locations

5 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 5 · Art. 38 CTR

Results and documents

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

Documents 122 files

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

Application history

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