Pancreatic Ductal Adenocarcinoma
Conditions
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.
Interventions
DRUGBI 765883
Participants received BI 765883 at doses of 0.4 mg/kg or 1.3 mg/kg, administered intravenously.
DRUGGemcitabine
Participants received gemcitabine at a dose of 1000 mg/m², administered intravenously
DRUGNab-paclitaxel
Participants received Nab-paclitaxel at a dose of 125 mg/m², administered intravenously
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Dose-Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period for the Determination of the Maximum Tolerated Dose (MTD) | The MTD evaluation period corresponds to the first two treatment cycles (28 days), with extension up to 35 days in cases of early discontinuation, based on the residual effect period. | All Dose-Limiting Toxicities (DLTs) were agreed upon by the Dose-Escalation Committee (DEC) after review of the data from each cohort. Only Dose-Limiting Toxicities (DLTs) occurring in the first 2 cycles were considered necessary for dose-escalation decisions made by the Dose-Escalation Committee (DEC). Dose-Limiting Toxicities (DLTs) observed during the Maximum Tolerated Dose (MTD) evaluation period were considered for Maximum Tolerated Dose (MTD) determination. The MTD evaluation period was defined as the first two treatment cycles; i.e. from Cycle 1 Day 1 (C1D1) up to and including the day before C3D1, or to the end of the REP in case of discontinuation before the start of C3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response as Defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | From the first trial drug administration until 35 days (the Residual Effect Period) after the last trial drug administration, covering a total duration of up to 134 days. | Objective Response is defined as the best overall response of complete response (CR) or partial response (PR), recorded from the start of the study treatment until the earliest of disease progression, death, or last evaluable tumor assessment, and before start of subsequent anti-cancer therapy. |
| Disease Control as Defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | From the first trial drug administration until 35 days (the Residual Effect Period) after the last trial drug administration, covering a total duration of up to 134 days. | Disease control (DC) was defined as complete response (CR), partial response (PR), or stable disease (SD) according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) from the start of treatment until the earliest of progressive disease (PD), death, or the last evaluable tumor assessment and before the start of subsequent anti-cancer therapy. |
| Objective Response (OR) as Assessed by the Investigator Defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | From the first trial drug administration until 35 days (the Residual Effect Period) after the last trial drug administration, covering a total duration of up to 134 days. | Objective response (OR) is defined as the best overall response of complete response (CR) or partial response (PR), recorded from the start of the study treatment until the earliest of progressive disease (PD), death, or the last evaluable tumor assessment, and before the start of subsequent anti-cancer therapy. |
| Maximum Measured Concentration of BI 765883 in Serum (Cmax) | Pharmacokinetic samples were collected predose (336 hrs after infusion start, prior to the next dose), at the start of infusion (0 hrs), after the end of infusion (0.5 hrs), and at 5, 24, 48, and 168 hrs after infusion start in Cycle 1 and Cycle 4. | The maximum measured concentration of the BI 765883 in serum is reported. |
| Area Under the Concentration-Time Curve of BI 765883 From Time 0 to 336 Hours (AUC₀-336) | Pharmacokinetic samples were collected predose (336 hrs after infusion start, prior to the next dose), at the start of infusion (0 hrs), after the end of infusion (0.5 hrs), and at 5, 24, 48, and 168 hrs after infusion start in Cycle 1 and Cycle 4. | The area under the serum concentration time curve of BI 765883 from time 0 to 336 hours is reported. |
Countries
Belgium, France, Germany, Japan, Spain, United States
Participant flow
Recruitment details
This open-label, non-randomized, first-in-human Phase Ia/Ib study evaluated BI 765883 as monotherapy and in combination with gemcitabine and nab-paclitaxel in patients with metastatic or relapsed pancreatic ductal adenocarcinoma. The study included dose escalation and planned expansion phases.
Pre-assignment details
The study was discontinued after safety concerns were observed at Dose Level 1 (DL1) in the combination cohort (BI 765883 0.4 mg/kg plus chemotherapy). A maximum tolerated dose (MTD) and a recommended dose for expansion (RDE) were not identified, and the planned Phase Ib expansion phase was not completed.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.6 Years STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 2 | 2 / 3 | 1 / 3 |
| other Total, other adverse events | 2 / 2 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 1 / 2 | 2 / 3 | 0 / 3 |
Outcome results
None listed