BI 905677 is a drug being developed for the treatment of cancer. The main purpose of this study is to investigate how the study drug BI 905677 spreads in the body and in the tumor. This is examined using a technique called Positron emission…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main objectives
The main objective of this study is to determine the tumour accumulation of
[89Zr]Zr-BI 905677 at baseline and during treatment.
Primary endpoint(s)
The primary endpoint is the relative change of SUVpeak (standard uptake value)
of [89Zr]Zr-BI 905677 in target tumour lesion(s) from baseline to post BI
905677 doses.
The relative change from baseline of the SUVpeak in target lesions is defined
as the average value at each of the last two imaging timepoints of the median
relative change from baseline of the SUVpeak in all target lesions.
The analysis of the primary endpoint will be descriptive and comparisons will
be based on
baseline (i.e. pre-treatment) values.
Please also see section 2.1 and 2.2 of the protocol.
Secondary outcome
There are no secondary endpoints in this study.
For further objectives and outcomes, please seen section 2.2 of the protocol.
Background summary
Despite the recent advancements in cancer treatment, cancer remains a leading
cause of death globally. In 2012 there were approximately 14 million new cancer
cases and 8.2 million cancer-related deaths worldwide and about 1,685,210 new
cancer cases were expected to be diagnosed in 2016. In the majority of cases,
the disease is diagnosed in late, advanced stages and the vast majority of the
patients progress on available treatments and
succumb to their disease. Therefore, there is a substantial need for novel
therapeutic agents and treatment strategies to improve the treatment outcome
for cancer patients.
LRP5 and LRP6, co-receptors of the Wnt ligands, are indispensable gatekeepers
for Wnt/ßcatenin pathway activation and are potential targets for effectively
inhibiting ligand mediated Wnt signalling in tumours. An antagonistic
bi-paratopic antibody, that binds LRP5 and LRP6 and blocks binding of Wnt
ligands, will block proliferation of malignant cells with ligandactivated Wnt
signalling and increase sensitivity to immunotherapy. Therefore, the
development of a LRP5/6 antagonist may constitute a valid therapeutic option
against cancer. The LRP5/LRP6 antagonist BI 905677 is a new biological entity
which is currently being studied in a Phase I dose finding trial
Please also see section 1.1 from the protocol.
Study objective
BI 905677 is a drug being developed for the treatment of cancer. The main
purpose of this study is to investigate how the study drug BI 905677 spreads in
the body and in the tumor. This is examined using a technique called Positron
emission tomography (PET scan). The research will also provide more information
about the safety of BI 905677.
See also sections 2.1 and 2.2 of the protocol.
Study design
This is a Phase I open label, non-randomized bio-distribution study which will
include patients with tumours harbouring an RNF43 mutation or R-Spondin fusion.
The trial is divided in two parts:
• Part 1 determines the tissue/organ distribution and dosimetry of [89Zr]Zr-BI
905677 and confirms the blockade of the [89Zr]Zr-BI 905677 uptake by BI 905677
at MTD as determined in the FIH Study 1401.0001.
• Part 2 will assess the tumour uptake of [89Zr]Zr-BI 905677 in combination
with various doses at and below MTD of BI 905677. This includes the
determination of the best ratio of [89Zr]Zr-BI 905677/BI 905677 to achieve an
optimal tumour penetration before the competition experiments start.
Furthermore, it should also explore the relationship between tumour uptake of
[89Zr]Zr-BI 905677 at baseline and tumour response.
During this biodistribution study, [89Zr]Zr-BI 905677 will be administered once
alone in Cycle 1.
In Cycle 1, additional cold mass dose of the mAb will be explored if needed for
imaging.
In Cycle 2, BI 905677 treatment at different doses in dedicated dose cohorts
will be administered preceding the second administration of [89Zr]Zr-BI 905677.
The doses of BI 905677 will be based on clinical data from the FIH trial
1401-0001. From Cycle 3 onwards, patients will be treated with BI 905677 at the
MTD (i.e. highest tolerable dose) determined in FIH Trial 1401-0001.
In Part 1, during Cycle 2, patients will receive BI 905677 at the MTD before
the [89Zr]Zr-
BI 905677 infusion.
In Part 2, during Cycle 2, different doses, lower than the MTD, of BI 905677
will be explored. At least 2 patients are needed in each dose cohort in order
to assess the degree of blockade of [89Zr]Zr-BI 905677 uptake by given BI
905677 doses. The dose levels will be decided by the SMC.
From Cycle 3, Day 1, patients will be treated at the MTD determined in FIH
Trial 1401.0001.
Also see section 3 and 4.1.2 of the protocol
Intervention
During this biodistribution study, [89Zr]Zr-BI 905677 will be administered once
alone in Cycle 1.
In Cycle 1, additional cold mass dose of the mAb will be explored if needed for
imaging.
In Cycle 2, BI 905677 treatment at different doses in dedicated dose cohorts
will be administered preceding the second administration of [89Zr]Zr-BI 905677.
The doses of BI 905677 will be based on clinical data from the FIH trial
1401-0001. From Cycle 3 onwards, patients will be treated with BI 905677 at the
MTD (i.e. highest tolerable dose) determined in FIH Trial 1401-0001.
In Part 1, during Cycle 2, patients will receive BI 905677 at the MTD before
the [89Zr]Zr-
BI 905677 infusion.
In Part 2, during Cycle 2, different doses, lower than the MTD, of BI 905677
will be explored. At least 2 patients are needed in each dose cohort in order
to assess the degree of blockade of [89Zr]Zr-BI 905677 uptake by given BI
905677 doses. The dose levels will be decided by the SMC.
From Cycle 3, Day 1, patients will be treated at the MTD determined in FIH
Trial 1401.0001.
Please also see section 4.1 of the protocol
Study burden and risks
Most patient in advanced and metastasized stages of cancer die due to the
progression of their disease. Therefore, there is a substantial need for novel
therapeutic agents and treatment strategies to improve the treatment outcome
for cancer patients.
LRP5 and LRP6, co-receptors of the Wnt ligands, are indispensable gatekeepers
for Wnt/ßcatenin pathway activation and are potential targets for effectively
inhibiting ligand mediated Wnt signalling in tumours. An antagonistic
bi-paratopic antibody, that binds LRP5 and LRP6 and blocks binding of Wnt
ligands, will block proliferation of malignant cells with ligandactivated Wnt
signalling and increase sensitivity to immunotherapy. Therefore, the
development of a LRP5/6 antagonist may constitute a valid therapeutic option
against cancer.
Comeniusstraat 6
Alkmaar 1817MS
NL
Comeniusstraat 6
Alkmaar 1817MS
NL
Listed location countries
Age
Inclusion criteria
1. Histologically or cytologically confirmed advanced, unresectable and/or
metastatic solid tumours with a documented RNF43 mutation or R-Spondin fusion
2.Failure to conventional treatment and no therapy of proven efficacy existing
or ineligibility for established Treatment options
3. Eastern Cooperative Oncology Group (ECOG) score: 0 to 1
4. At least one Positron emmission tomography (PET)-imageable, evaluable tumor
lesion (>=20 mm) according to Revised Response Evaluation Criteria in Solid
Tumors (RECIST) Version 1.1
5. At least one biopsiable tumor lesion
6. Life expectancy of at least 12 weeks after the start of the treatment
according to the Investigator*s judgement
Exclusion criteria
1. Major surgery performed within 4 weeks prior to first Trial treatment or
planned within 6 months after Screening
2. Previous or concomitant malignancies other than the one treated in this
trial within the last 2 years
3. Osteoporosis >= Common Terminology Criteria for Adverse Events (CTCAE) Grade
2 or osteoporotic compression fracture within 12 months prior to informed
consent
4. Treatment with an anti-cancer therapy or investigational drug within 28 days
or 5 half-lives of the first treatment with the study medication
5. Presence or history of uncontrolled or symptomatic brain or subdural
metastases
6. History of human immunodeficiency virus (HIV) infection or an active
hepatitis B or C infection
7. History of severe hypersensitivity reactions to monoclonal antibodies or
allergy to kanamycin or similar class drugs
8. Women who are pregnant, nursing, or who plan to become pregnant or nursing
during the trial or within 6 months after the last dose of study treatment
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-002659-41-NL |
| ClinicalTrials.gov | NCTnummeropditmomentnognietbekend |
| CCMO | NL73333.029.20 |