A Trial to Find the Safe Dose for BI 905681 in Patients With Incurable Tumours or Tumours That Have Spread

NCT04147247 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 1424-00012019-003490-25
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objective of this trial is to determine the maximum tolerated dose (MTD)/optimal biological dose (OBD) of BI 905681 given as an intravenous infusion and to determine the recommended dose and dosing schedule for further trials in the development of BI 905681. The MTD will be defined based on the frequency of patients experiencing dose-limiting toxicities (DLTs) during the MTD/DLT evaluation period, which is defined as the first cycle of treatment. Separate MTDs will be determined for Schedule A and Schedule B. The secondary objective of the trial is to determine the pharmacokinetic (PK) profile of BI 905681.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• The Maximum Tolerated Dose (MTD)/Optimal Biological Dose (OBD) of BI 905681

  The MTD/OBD of BI 905681. The MTD will be assessed based on the number of patients experiencing Dose Limiting Toxicities (DLTs), graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, in the first cycle of treatment (3 weeks). The MTD is defined as the highest dose with less than 25% risk of the true DLT rate being equal to or above 33%.

  The first cycle of treatment, up to 21 days.

• Number of Patients Experiencing Adverse Events (AEs) During the Entire Treatment Period

  Number of patients experiencing adverse events (AEs) during the entire treatment period.

  From the first administration of study till the last administration of study drug +42 days, up to 126 days.

Secondary Outcomes (2)

• Cmax: Maximum Measured Concentration of BI 905681 in Serum After First Infusion

  5 minutes before and 1, 1.5, 4, 8, 24, 72, 168, 336 and 504 (5 minutes before 2nd infusion) hours following the first infusion.

• AUC0-tz: Area Under the Serum Concentration-time Curve Over the Time Interval From 0 to the Last Measured Time Point (tz)

  5 minutes before and 1, 1.5, 4, 8, 24, 72, 168, 336 and 504 (5 minutes before 2nd infusion) hours following the first infusion.

Study Arms (5)

1.0 milligram/kilogram BI 905681

EXPERIMENTAL

Subjects received an intravenous infusion of 1.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.

Drug: BI 905681

2.5 milligram/kilogram BI 905681

EXPERIMENTAL

Subjects received an intravenous infusion of 2.5 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.

Drug: BI 905681

5.0 milligram/kilogram BI 905681

EXPERIMENTAL

Subjects received an intravenous infusion of 5.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.

Drug: BI 905681

7.0 milligram/kilogram BI 905681

EXPERIMENTAL

Subjects received an intravenous infusion of 7.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.

Drug: BI 905681

8.5 milligram/kilogram BI 905681

EXPERIMENTAL

Subjects received an intravenous infusion of 8.5 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.

Drug: BI 905681

Interventions

BI 905681 DRUG

Infusion

1.0 milligram/kilogram BI 905681; 2.5 milligram/kilogram BI 905681; 5.0 milligram/kilogram BI 905681; 7.0 milligram/kilogram BI 905681; 8.5 milligram/kilogram BI 905681

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-haematologic malignancy. Patient must have measurable or evaluable lesions (according to Response Evaluation Criteria in Solid Tumours (RECIST) v 1.1).
• Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options.
• Patients willing to undergo mandatory tumour biopsy at the time points specified in the protocol.
• Eastern Cooperative Oncology Group (ECOG) Score of 0 or 1 (R01-0787).
• Adequate organ function defined as all of the following:
• Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L; haemoglobin ≥9.0 g/dL; platelets ≥100 x 10\^9/L without the use of haematopoietic growth factors within 4 weeks of start of study medication.
• Total bilirubin ≤1.5 x the upper limit of normal (ULN), except for patients with Gilbert's syndrome: total bilirubin ≤3 x ULN or direct bilirubin ≤1.5 x ULN.
• Creatinine ≤1.5 x ULN. If creatinine is \>1.5 x ULN, patient is eligible if concurrent creatinine clearance ≥50 ml/min (measured or calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula or Japanese version of CKD-EPI formula for Japanese patients).
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 x ULN if no demonstrable liver metastases, or otherwise ≤5 x ULN
• Alkaline Phosphatase (ALP) \<5 x ULN
• At least 18 years of age at the time of consent or over the legal age of consent in countries where that is greater than 18 years.
• Signed and dated written informed consent in accordance with International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP) and local legislation prior to admission to the trial
• Life expectancy ≥3 months at the start of treatment in the opinion of the investigator

You may not qualify if:

• Osteoporosis ≥ CTCAE Grade 2
• Osteoporotic compression fracture within 12 months prior to informed consent which is clinically significant in the opinion of the investigator.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms

Limitations and Caveats

Trial was prematurely discontinued due to limited antitumor activity (i.e., lack of a single objective response) \& difficulty in enrolling patients with RNF43 (Ring Finger Protein 43) mutations or R-spondin fusions who were willing to undergo a biopsy. The trial aimed to test two schedules for BI 905681 (A: every three weeks in a 3-week cycle, B: every 2 weeks in a 4-week cycle). Maximum tolerated dose/Recommended Phase 2 dose for Schedule A could not be determined, schedule B was not pursued.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2019
• First Posted: November 1, 2019
• Study Start: December 23, 2019
• Primary Completion: May 6, 2021
• Study Completion: May 27, 2021
• Last Updated: November 29, 2023
• Results First Posted: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)