Clinical trial NCT05087992: A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers
Official title: A Phase Ia/Ib, Open Label, Multicentre, Dose Escalation Study of BI 905711 in Combination With Chemotherapy Followed by Expansion Cohorts in Patients With Advanced Gastrointestinal Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastrointestinal Cancer, Metastatic
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-10-21
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1a non randomized, Phase 1b randomized.
Primary purpose: TREATMENT

Brief summary: This study is open to adults with advanced colorectal cancer or with advanced pancreatic cancer. The study has 2 parts. In the first part, participants with colorectal cancer get a medicine called BI 905711 combined with chemotherapy and bevacizumab. The purpose of the first part is to find the highest BI 905711 dose participants can tolerate. In the second part, participants with colorectal cancer or pancreatic cancer get BI 905711 combined with chemotherapy. Some participants also get bevacizumab. The second part tests whether BI 905711 makes tumours shrink. Participants get BI 905711, chemotherapy and bevacizumab about every 2 weeks as an infusion into a vein. Participants can stay in the study as long as they benefit from treatment and can tolerate it. The doctors regularly check the health of the participants and note any health problems that could have been caused by the study treatment. The doctors also monitor the size of the tumour.


Eligibility criteria: Inclusion Criteria:

* Signed and dated written informed consent in accordance with International Council of Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
* Of legal adult age (according to local legislation) at screening.
* Histologically or cytologically confirmed, advanced unresectable or metastatic colorectal adenocarcinoma.
* Colorectal adenocarcinoma (CRC): Patients who have Progressive disease (PD) after prior oxaliplatin-based first line therapy or within 6 months after the end of oxaliplatin-based adjuvant therapy.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
* Life expectancy ≥ 3 months in the opinion of the investigator.
* Availability and willingness to provide tumor tissue (fresh biopsy or archival) for biomarker analysis. Only non-significant risk procedures per the investigator's judgment will be used to obtain any biopsies specified in this study. In case a fresh tumor biopsy cannot be obtained, the recruitment of the patient may proceed on a case-by-case basis after agreement between the investigator and BI. In such a case, an archived tumor tissue specimen must be submitted.
* Adequate hepatic, pancreatic, renal and bone marrow functions as defined by all of the below:

  * Total bilirubin ≤ 1.5 x institutional upper level of normal (ULN).
  * Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤2.5 x institutional ULN or ≤5 x institutional ULN for patients with known liver metastases.
  * Serum creatinine ≤1.5x institutional ULN. If creatinine is \> 1.5 x ULN, patient is eligible if concurrent creatinine clearance ≥ 50 ml/min (≥ 0.05L/min) (measured or calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula or Japanese version of CKD-EPI formula for Japanese patients).
  * Absolute neutrophil count (ANC) ≥ 1.5 x 1\^9/L, ≥ 1.5 x 10\^3/μL, or ≥ 1500/mm\^3
  * Platelets ≥ 100 x 10\^9/L, ≥ 100 x 10\^3/μL, or ≥ 100 x 10\^3/mm\^3
  * Hemoglobin (Hb) ≥ 8.5 g/dl, ≥ 85 g/L, or ≥ 5.3 mmol/L (without transfusion within previous week) Serum lipase ≤ 1.5 institutional ULN (Only for CRC cohort); \>1.5 - 2.0 x ULN or asymptomatic \>2.0 - 5.0 x ULN if related to Pancreatic Ductal Adenocarcinoma (PDAC) (Only for PDAC cohort) Further inclusion criteria apply.

Exclusion criteria:

* Any prior irinotecan-based therapy in the metastatic setting.
* Previous systemic anti-cancer therapy within the specified timeframe from the last dose intake to the first dose of trial treatment as follows:

  * Any non-investigational drug, including anti-angiogenic agents (bevacizumab or ramucirumab or aflibercept) and anti-EGFR antibodies (cetuximab or panitumumab), within 14 days.
  * Any investigational drug or other antibodies including immune checkpoint inhibitors, within 28 days.
* Currently enrolled in another investigational device or drug trial. Patients who are in follow-up/observation for another clinical trial are eligible.
* Radiation therapy within 4 weeks prior to start of treatment. However, palliative radiotherapy for symptomatic metastasis is allowed if completed within 2 weeks prior to start of treatment.
* 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 or active ulcers (gastro-intestinal (GI) tract, skin) 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.
* Known pathological condition of GI tract, liver and pancreas, excluding the disease under study, that may interfere with assessment of drug safety or may increase the risk of toxicity:

  * inflammatory bowel disease
  * chronic pancreatitis
  * other serious GI pathological conditions by judgment of the investigator e.g. autoimmune disease with GI involvement, unexplained active diarrhea CTCAE v5.0 grade ≥ 2.
* Known history of human immunodeficiency virus (HIV) infection.
* Any of the following laboratory evidence of hepatitis virus infection. Test results obtained in routine diagnostics are acceptable if done within 14 days before the informed consent date:

  * Positive results of hepatitis B surface (HBs) antigen
  * Presence of HBc antibody together with hepatitis B virus deoxyribonucleic acid (HBV-DNA)
  * Presence of hepatitis C ribonucleic acid (RNA) Further exclusion criteria.

Primary outcomes:
measure: Determination of the Maximum Tolerated Dose (MTD) of BI 905711
timeFrame: From cycle 1 Day 1 until the day before cycle 3 Day 1 (2 14-day treatment cycles), or end of the residual effect period (REP) (30 days + 5 days) in case of discontinuation before start of cycle 3, up to 35 days.
measure: Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation
timeFrame: From cycle 1 Day 1 until the day before cycle 3 Day 1 (2 14-day treatment cycles), or end of the REP (30 days + 5 days) in case of discontinuation before start of cycle 3, up to 35 days.
measure: Confirmed Objective Response (OR)
timeFrame: From the first administration of trial medication until the earliest of progressive disease (PD), death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, up to 54 weeks.
measure: Number of PDAC Patients With DLTs During the MTD Evaluation Period Assessed in the First 6 Patients
timeFrame: From cycle 1 Day 1 until the day before cycle 3 Day 1 (2 14-day treatment cycles), or end of the REP (30 days + 5 days) in case of discontinuation before start of cycle 3, up to 35 days.
Secondary outcomes:
measure: Maximum Measured Plasma Concentration of BI 905711 During the First Cycle (Cmax)
timeFrame: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
measure: Maximum Measured Plasma Concentration of BI 905711 After Multiple Cycles (Cmax)
timeFrame: Cycle 3: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
measure: Area Under the Concentration-time Curve in Plasma of BI 905711 During the First Cycle (AUC0-336)
timeFrame: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
measure: Area Under the Concentration Time-curve in Plasma of BI 905711 After Multiple Cycles (AUC0-336)
timeFrame: Cycle 3: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
measure: Progression Free Survival (PFS)
timeFrame: From date of start of treatment to the date of disease progression or death, whichever is earlier as assessed by the investigator according to RECIST 1.1., up to 54 weeks.
measure: Maximum Percentage Change From Baseline in the Sum of Longest Target Lesion Diameters
timeFrame: At baseline and every 8 weeks (± 7 days) until progression or start of further treatment for disease, up to 54 weeks.
measure: Duration of Objective Response (OR)
timeFrame: From the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or PD is objectively documented, up to 54 weeks.
measure: Disease Control
timeFrame: From the start of treatment until the earliest of PD, death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy, up to 54 weeks.
measure: Maximum Measured Plasma Concentration of BI 905711 During the First Cycle (Cmax) in Phase Ib
timeFrame: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
measure: Maximum Measured Plasma Concentration of BI 905711 After Multiple Cycles (Cmax) in Phase Ib
timeFrame: Cycle 3: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
measure: Area Under the Concentration-time Curve of BI 9057 During the First Treatment Cycle (AUC0-t2) in Phase Ib
timeFrame: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
measure: Area Under the Concentration-time Curve of BI 9057 After Multiple Cycles (AUC0-t2) in Phase Ib
timeFrame: Cycle 3: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Leuven
country: Belgium
facility: UZ Leuven
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Poitiers
country: France
facility: HOP la Milétrie
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
Study officials:
References: