Phase 1
N=174
BI 894999 First in Human Dose Finding Study in Advanced Malignancies
Neoplasms · NUT Carcinoma
Bottom Line
View on ClinicalTrials.gov: NCT02516553 ↗Enrolled (actual)
174
Serious AEs
55.8%
Results posted
Apr 2024
Primary outcome: Primary: Phase Ia: Number of Patients With DLTs Observed in the First Cycle — 0; 0; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- BI 894999 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Boehringer Ingelheim
- Primary completion
- Nov 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase Ia: Number of Patients With DLTs Observed in the First Cycle |
0; 0; 0; 0; 3; 2 | — |
| PRIMARY Phase Ib: Number of Patients With DLTs Observed During the On-treatment Period |
3; 2; 7; 2; 3 | — |
| SECONDARY Phase Ia: Number of Patients With DLTs Observed During the On-treatment Period |
0; 0; 0; 2; 4; 2 | — |
| SECONDARY Phase Ia and Phase Ib: Area Under the Concentration-time Curve of BI 894999 in Plasma Over the Time Interval From 0 to 24 Hours After Administration of the First Dose (AUC0-24) |
4.36; 6.43; 20.5; 34.0; 64.9; 27.7 | — |
| SECONDARY Phase Ia and Phase Ib: Maximum Measured Concentration of BI 894999 in Plasma After the First Dose (Cmax) |
0.393; 0.569; 1.75; 3.79; 7.39; 16.2 | — |
| SECONDARY Phase Ia and Phase Ib: Area Under the Concentration-time Curve of BI 894999 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ, ss) |
10.3; 17.9; 54.6; 76.4; 119; NA | — |
| SECONDARY Phase Ia and Phase Ib: Maximum Measured Concentration of BI 894999 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax, ss) |
0.697; 1.26; 4.06; 5.25; 11.6; NA | — |
| SECONDARY Phase Ia and Phase Ib: Objective Response (OR) |
0; 1; 0; 1; 0; 0 | — |
| SECONDARY Phase Ib: Progression-free Survival or (PFS) or Radiological PFS for mCRPC Patients With Non-measurable Disease by RECIST v1.1 |
5.6; 5.6; 11.9; 6.9; 7.8 | — |
| SECONDARY Phase Ib: Best Overall Response |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Phase Ib: Overall Survival |
6.6; 15.4 | — |
| SECONDARY Phase Ib: Prostate Specific Antigen (PSA) Response in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) |
— | — |
Summary
This study is open to adults with different types of advanced cancer (solid tumours). The study is also open to patients with diffuse large B-cell lymphoma in whom previous treatment was not successful. In some countries, adolescents who are at least 15 years old and who are diagnosed with NUT carcinoma can also participate. No standard treatment exists for this rare and aggressive form of cancer.
The purpose of this study is to find out the highest dose of BI 894999 that people can tolerate.
BI 894999 is tested for the first time in humans. Participants take tablets once daily. The study also tests whether participants can tolerate BI 894999 better when taken continuously or with breaks in between.
Participants can stay in the study as long as they benefit from the treatment and can tolerate it.
The doctors also regularly check the general health of the participants.
Eligibility Criteria
Inclusion criteria
For all patients
- Age 18 years or older at the time of signature of the informed consent.
- Life expectancy of at least 12 weeks after the start of the treatment according to the investigator's judgement
- Male or female patients. Women of childbearing potential* must be ready 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. A list of contraception methods meeting these criteria is provided in the patient information. For women of childbearing potential using a contraceptive pill, an additional barrier method is necessary due to the potential CYP3A4 inducing effect of BI894999. Male patients having a partner of childbearing potential must use condoms and ensure their partner is using a highly effective method of birth control as described above, during the trial and for at least three months after the end of the trial * Any female who has experienced menarche and does not meet the criteria for "women not of childbearing potential" as described below.
Women not of childbearing potential are defined as: women who are postmenopausal (12 months with no menses without an alternative medical cause) or who are permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy).
- Written informed consent consistent with ICH-GCP and local legislation
For patients with solid tumours
- Patients with a histologically or cytologically confirmed diagnosis of an advanced unresectable and/or metastatic, malignant solid tumour, who have failed conventional treatment or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies
- Age ≥ legal age to be adult for the given country at the time of signature of the informed consent. For NC patients, age 15 years or older at the time of signature of the informed consent ( in Germany and South Korea, only legally adult patients may be included
- Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0 or 1 at the time of screening. A score of 2 is allowed for NUT carcinoma patients
- Recovery of therapy-related toxicities from previous chemotherapy, tyrosine kinase inhibitors, hormone therapy, immunotherapy, antibodies, vaccine therapy, or radiotherapy to CTCAE ≤ grade 1 (with the exception of alopecia, peripheral sensory neuropathy grade 2)
- Life expectancy of at least 12 weeks after the start of the treatment according to the investigator's judgement
- Male or female patients. Women of childbearing potential* must be ready 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. A list of contraception methods meeting these criteria is provided in the patient information. For women of childbearing potential using a contraceptive pill, an additional barrier method is necessary due to the potential CYP3A4 inducing effect of BI894999. Male patients having a partner of childbearing potential must use condoms and ensure their partner is using a highly effective method of birth control as described above, during the trial and for at least three months after the end of the trial treatment
- Written informed consent consistent with ICH-GCP and local legislation. For adolescent NC patients aged 15 years to than PSA no. 2; if not, a fourth PSA (PSA no. 4) is required to be > to PSA no. 2
In patients with DLBCL
- Patients with histologically confirmed DLBCL who have failed 2 or more lines of systemic therapy including an anti-CD-20 therapy and an anthracycline or who are not amenable to standard therapies but have an indication for therapy as per investigator's judgement. Standard therapies may also include but are not limited to CAR-T cells therapy, depending on approved therapies in the country where the patient is treated
- ECOG Performance Status 0, 1 or
Data sourced from ClinicalTrials.gov (NCT02516553). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.