Clinical trial NCT06528093: A Study to Find a Suitable Dose of BI 765883 and to Test Whether it Helps People With Advanced Pancreatic Cancer When Taken Alone or Together With Chemotherapy
Official title: A First-in-human Open Label Phase Ia/Ib, Multicenter/Multiregional, Dose Escalation Study of BI 765883 Administered Intravenously as Monotherapy and in Combination With Gemcitabine and Nab-paclitaxel in Unselected Patients With Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) or Patients With PDAC Who Have Relapsed After Post-surgery Adjuvant Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Pancreatic Ductal Adenocarcinoma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2024-07-30
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is open to adults with advanced pancreatic cancer for whom previous treatment was not successful or no treatment exists.

The purpose of this study is to find the highest dose of BI 765883 that people with advanced pancreatic cancer can tolerate when taken alone or together with chemotherapy. Another purpose is to check whether BI 765883 helps people with advanced pancreatic cancer. In this study, BI 765883 is given to humans for the first time.

Participants receive either BI 765883 alone or BI 765883 in combination with chemotherapy. Participants can stay in the study as long as they benefit from treatment and can tolerate it. At study visits, doctors collect information on any health problems of the participants and check the severity of participants' cancer.


Eligibility criteria: Inclusion Criteria:

1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
2. Of legal adult age (according to local legislation) at screening
3. Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be willing and able to use highly effective 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.
4. Histologically or cytologically confirmed Pancreatic ductal adenocarcinoma (PDAC)
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
6. Life expectancy ≥3 months in the opinion of the investigator
7. Archived tumor tissue from a tissue core biopsy (e.g. paraffin-embedded formalin-fixed tissue blocks), OR fresh tumor tissue available for retrospective biomarker analysis; in both cases, a minimum of at least two core needle biopsies (18 gauge or greater) is required. Only non-significant risk procedures per the investigator's judgment will be used to obtain any biopsies specified in this study in cases where a fresh tumor biopsy is required.
8. Patients with at least 1 target lesion that can be accurately measured per RECIST version 1.1 Further inclusion criteria apply.

Exclusion Criteria:

1. Previous exposure to trial drug (BI 765883)
2. Any prior gemcitabine and/or paclitaxel therapy (for combination therapy cohorts)
3. Known hypersensitivity to the study medications or their excipients (including gemcitabine and nab-paclitaxel)
4. Any contraindications to gemcitabine or nab-paclitaxel according to the current approved local labels (combination therapy)
5. Currently enrolled in another investigational device or drug trial, or less than 28 days since ending another investigational device or drug trial(s) or receiving other investigational treatment(s)
6. Any serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as neurologic, psychiatric, infectious disease, active ulcers (gastrointestinal tract, skin), inflammatory bowel disease or bowel infection, or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the Investigator, would make the patient inappropriate for entry into the trial.
7. Prior radiotherapy or systemic therapy within 14 days prior to treatment start
8. History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of ≥III or IV, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the Investigator Further exclusion criteria apply.

Primary outcomes:
measure: Occurrence of dose limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period
timeFrame: Up to 28 days (2 treatment cycles)
measure: Confirmed objective response (OR)
timeFrame: Up to 350 days (25 treatment cycles)
Secondary outcomes:
measure: Objective response (OR)
timeFrame: Up to 350 days (25 treatment cycles)
measure: Recommended dose for expansion (RDE) for BI 765883 in combination with gemcitabine and nab-paclitaxel
timeFrame: Up to 28 days (2 treatment cycles)
measure: Frequency and severity of AEs according to the Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Up to 350 days (25 treatment cycles)
measure: Maximum measured concentration of the analyte in serum (Cmax)
timeFrame: Up to 350 days (25 treatment cycles)
measure: Area under the serum concentration time curve of the analyte (AUC0-t)
timeFrame: Up to 350 days (25 treatment cycles)
measure: Progression-free survival (PFS)
timeFrame: Up to 350 days (25 treatment cycles)
measure: Duration of response (DOR)
timeFrame: Up to 350 days (25 treatment cycles)
Other outcomes:
Locations:
city: Denver
country: United States
facility: HealthONE
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Sarasota
country: United States
facility: Florida Cancer Specialists-Sarasota-61670
state: Florida
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Bruxelles
country: Belgium
facility: Brussels - UNIV Saint-Luc
city: Leuven
country: Belgium
facility: UZ Leuven
city: Lyon
country: France
facility: CTR Leon Berard
city: Rennes
country: France
facility: CTR Eugène Marquis
city: Villejuif
country: France
facility: INS Gustave Roussy
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg, Eppendorf
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: München
country: Germany
facility: Klinikum der Universität München AÖR
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Tokyo, Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
Study officials:
References: