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

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Gastrointestinal Cancer, Metastatic

Treatments: Drug: BI 905711; Drug: Bevacizumab; Drug: FOLFIRI

Study type: Interventional

Funder types: Industry

Identifiers

NCT05087992

2021-003041-37 (EudraCT Number)

1412-0003

Details and patient eligibility

About

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.

Enrollment: 13 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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13 participants in 3 patient groups

0.6 mg/kg BI 905711 + FOLFIRI + bevacizumab

Experimental group

Description:

Patients with colorectal adenocarcinoma (CRC) received a single administration of 0.6 milligrams (mg) / kilograms (kg) of BI 905711 intravenously on Day 3 of each 14-day cycle. Patients also received FOLFIRI (irinotecan: 180 mg/squaremeters (m2) over 1.5 hours (hrs), leucovorin: 400 mg/m2 (in Japan: levoleucovorin: 200 mg/m2) over 2 hrs, fluorouracil: 400 mg/m2 bolus or 2400 mg/m2 46 hrs continuous infusion) in combination with bevacizumab, 5 mg/kg over 30 minutes (min) intravenously on Day 1 of each 14-day cycle.

Treatment:

Drug: Bevacizumab

Drug: FOLFIRI

Drug: BI 905711

1.2 mg/kg BI 905711 + FOLFIRI + bevacizumab

Experimental group

Description:

Patients with colorectal adenocarcinoma (CRC) received a single administration of 1.2 mg/kg of BI 905711 intravenously on Day 3 of each 14-day cycle. Patients also received FOLFIRI (irinotecan: 180 mg/m2 over 1.5 hours (hrs), leucovorin: 400 mg/m2 (in Japan: levoleucovorin: 200 mg/m2) over 2 hrs, fluorouracil: 400 mg/m2 bolus or 2400 mg/m2 46 hrs continuous infusion) in combination with bevacizumab, 5 mg/kg over 30 minutes (min) intravenously on Day 1 of each 14-day cycle.

Treatment:

Drug: Bevacizumab

Drug: FOLFIRI

Drug: BI 905711

FOLFIRI + bevacizumab

Active Comparator group

Description:

Patients with colorectal adenocarcinoma (CRC) received FOLFIRI (irinotecan: 180 mg/m2 over 1.5 hours (hrs), leucovorin \[or levoleucovorin\]: 400 mg/m2 (in Japan: levoleucovorin: 200 mg/m2) over 2 hrs, fluorouracil: 400 mg/m2 bolus or 2400 mg/m2 46 hrs continuous infusion) in combination with bevacizumab, 5 mg/kg over 30 minutes (min) intravenously on Day 1 of each 14-day cycle.

Treatment:

Drug: Bevacizumab

Drug: FOLFIRI