Primary: The primary objective of this study is to determine the biomarker status of patients screened in this master screening study and their potential biomarker eligibility to participate in a linked Roche clinical trial.Exploratory:The…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Proportion of patients with evaluable biomarker results
- Proportion of patients who are identified as being biomarker eligible for a
linked Roche clinical trial
Secondary outcome
- Prevalence of selected biomarkers in the screened population according to
disease indication
- Prevalence of selected biomarkers in the screened population summarized by
demographic or clinical features, including but not limited to, disease
indication or stage, geographic location, and prior cancer therapy
- Characterization of next treatment according to disease indication and
biomarker profile
Background summary
Study BX43361 is a screening study that provides tissue biomarker testing to
determine
enrolled patients* potential eligibility in order based on their biomarker
status (biomarker
eligibility) for a Roche-sponsored clinical trial linked to this master
screening study.
Initially, this screening study will utilize this common screening approach to
support
enrollment in the two platform Studies BO42777 and BO43249 only. However, the
Sponsor ultimately envisions an expansion of the scope of the clinical trials
and
oncological indications that will be served by this biomarker screening study
Improved understanding of the role of cancer biomarkers underpins the rational
development of molecularly targeted therapies for selected patient populations.
This
includes the understanding of cancer immunotherapy (CIT), which has progressed
rapidly within the last few years.
Assigning treatments that specifically target actionable oncogenic drivers is
the
cornerstone of precision oncology. Oncogenic driver alterations play a critical
role in cancer development and maintenance and are typically mutually
exclusive. Driver alterations in specific kinases can result in constitutive
activity that can drive the initiation and progression of malignancies.
Identification of oncogenic drivers through clinical genotyping can aid in
diagnoses and utilization of targeted therapies for the treatment of many
different cancer types at different disease stages.
It has been observed that patients identified as having an actionable oncogenic
driver alteration
derive greater treatment benefit from appropriate targeted therapies which tend
to be
more tolerable compared to conventional, non-targeted treatments.
This has led to approvals of multiple targeted oncological treatments and their
inclusion
in treatment guidelines across multiple tumor types, including NSCLC.
These improvements in the standard of care (SOC) for selected patients across a
wide
spectrum of solid tumors support the evaluation of additional targeted
therapies in
biomarker-defined populations to address unmet medical needs of patients with
both
advanced and early-stage disease.
CIT has demonstrated clear clinical efficacy, with significant survival benefit
observed
across multiple advanced malignancies..
The importance of CIT in earlier stages of lung cancer has been demonstrated by
the
approval of durvalumab (effect on PD-L1) in the United States and European
Union for use as
consolidation treatment for patients with Stage III locally advanced,
unresectable NSCLC
who have not progressed after chemoradiation according to local label
In addition, atezolizumab was recently approved for use as adjuvant therapy
after curative intent surgery in NSCLC.
Recommendations for biomarker testing for advanced or metastatic disease are
clear
and have become the SOC where approved targeted therapies exist. However,
biomarker testing is performed less frequently as a routine in early disease.
BX43361 will determine the biomarker status and identify biomarker-eligible
patients for enrollment into linked Roche clinical trials, using centralized,
indication-appropriate molecular testing and PD-L1 immunohistochemistry (IHC)
testing.
This aims to facilitate clinical trial access for patients to appropriate
investigational
therapies, based on biomarker status. This may be particularly helpful at
investigational
sites where the required biomarker testing is not available as part of SOC.
The use of a master screening study across multiple Roche clinical trials
ensures a
consistent, high-quality, central method of biomarker testing to determine a
patient*s
biomarker status across a number of disease-relevant biomarkers simultaneously.
This
coordinated approach aims to reduce screen failure rates compared with those for
individual biomarker-specific testing within a single investigational treatment
trial. It will
provide a more efficient, streamlined recruitment process, consistent with the
advantages of using master protocol study designs.
See protocol pages 15-19
Study objective
Primary:
The primary objective of this study is to determine the biomarker status of
patients screened in this master screening study and their potential biomarker
eligibility to participate in a linked Roche clinical trial.
Exploratory:
The exploratory objectives are:
- To characterize the biomarker profiles of all screened patients according to
disease indication
- To collect the details of the patients* next treatment according to disease
indication and biomarker status
Study design
Male and female patients age 18 years and above who have provided informed
consent and meet
all the eligibility criteria of the study, will be eligible for biomarker
testing.
The screening period of the study is from Day -28 to Day 1, during which time
eligibility
should be assessed. A biopsy must be performed prior to any chemoradiation, or
other anti-cancer treatment begins.
Patients with an eligible biomarker profile are then able to consider
participation in the relevant linked Roche clinical trial, if a treatment
cohort appropriate for the patient*s biomarker profile is open for recruitment.
For patients who consent to participate in a linked Roche clinical trial and
are eligible, remaining samples collected during this screening study will be
linked with the treatment study.
A study follow-up completion visit should be conducted within approximately 6
months
after receiving results from biomarker testing, for collection of the patient*s
next treatment information, if available.
See protocol page 22.
Intervention
Possible biopsy (if not sufficient material available and if deemed appropriate
as per investigator) and blood sampling.
Study burden and risks
The patients* health will not improve from this screening, but the results from
the biomarker testing may enable patients to participate in a Roche research
study in the future. In addition, the information that is learned may help
other people who have a similar medical condition in the future.
Patients may have side effects from the procedures used. Depending on the
procedure(s), side effects can be mild to severe and even life threatening, and
they can vary from person to person. This is documented in the patient
information sheet_informed consent form.
Beneluxlaan 2A
Woerden 3446AA
NL
Beneluxlaan 2A
Woerden 3446AA
NL
Listed location countries
Age
Inclusion criteria
General Inclusion Criteria
Patients must meet the following criteria for study entry:
- Signed Informed Consent Form
- Age 18 years or above at time of signing Informed Consent Form
- Given that the aim of Study BX43361 is to assign patients to a
biomarker-appropriate linked Roche clinical trial:
- Awareness of and willingness, in principle, to participate in an assigned
cohort of a linked Roche clinical trial
- Ability to comply with future investigational treatment protocol procedures
in the investigator*s judgment and based on discussion with the patient, for
example, dosing of medication (e.g., oral or IV), tumor assessments, safety
monitoring, agreement to meet contraceptive requirements, and completion of
questionnaires
- Confirmed availability of a representative formalin-fixed, paraffin-embedded
(FFPE) tumor specimen.
- Adequate hematologic and end-organ function by the investigator*s clinical
judgement, including the following:
- No clinically significant hematologic (CBC), coagulation, or biochemistry
test results
- No indications and/or known history of clinically significant acute or
chronic liver, or kidney injury
Stage-Specific Inclusion Criteria
Patients with Stage III NSCLC
Patients with Stage III NSCLC must meet the following criteria for study entry:
- Locally advanced, unresectable Stage III NSCLC of either squamous or
non-squamous histology based on 8th edition of the American Joint Committee on
Cancer (AJCC) and Union for International Cancer Control (UICC) cancer staging
system with plans to receive, currently receiving, or received chemoradiation
treatment
- Representative FFPE tumor specimen obtained prior to the start of any
chemoradiotherapy
- Eastern Cooperative Oncology Group (ECOG) Group Performance Status of 0, 1, or
2
Patients with Stage II, IIIA or Select IIIB (T3N2 only) NSCLC Requiring
Adjuvant Treatment
Patients with Stage I to IIIA NSCLC must meet the following criteria for study
entry:
- Stage I to IIIA NSCLC based on the 8th edition of the AJCC and UICC cancer
staging system
- Considered eligible for curative intent surgery (complete resection with all
surgical margins testing negative for tumor).
- Screening within Study BX43361, using a pretreatment biopsy, is encouraged to
be performed as early in the patient treatment pathway as possible to ensure
the patient is potentially eligible for all cohorts
• Representative FFPE tumor specimen obtained prior to the start of
o For patients enrolled following surgery:
These patients should achieve complete resection of histologically confirmed
Stage I to Stage IIIA with all surgical margins testing negative for tumor.
o It is strongly recommended that patients should be enrolled no more than 8
weeks after surgery, and prior to post-operative chemotherapy (as applicable).
Investigators should make reference to the relevant linked Roche clinical trial
protocol to ensure sufficient time is given to subsequently screen the patient
within the linked trial for biomarker-eligible patients identified.
- For patients enrolled prior to surgery:
There must be sufficient tumor biopsy tissue available for evaluation prior to
the start of any anti-cancer treatment (if receiving neoadjuvant therapy).
- Representative FFPE tumor specimen obtained prior to the start of any
treatment
- ECOG Performance Status of 0 or 1
Exclusion criteria
General Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study
entry:
- Pregnant or breastfeeding, or intending to become pregnant during the study
Women of childbearing potential who are required (and have consented) to have a
study-mandated procedure for which pregnancy would impact the risks to the
patient and/or fetus per local guidelines must have a negative serum pregnancy
test result within 7 days prior to the procedure.
- History of malignancy other than NSCLC within 5 years prior to screening,
except for malignancies with a negligible risk of metastasis or death
- Any other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding that contraindicates the use of an investigational
drug, may affect the interpretation of the results, or may render the patient
at high risk from treatment complications. This includes any of the following:
o Known clinically significant liver disease (e.g., active viral, alcoholic, or
other hepatitis; cirrhosis; current alcohol abuse)
o Significant cardiovascular disease (e.g., New York Heart Association Class II
or greater cardiac disease, myocardial infarction, or cerebrovascular accident)
within 3 months prior to enrollment, unstable arrhythmia, or unstable angina
- Recent major surgical procedure or anticipation of a need for a major
surgical procedure, except for patients who have recently had and have adequate
healing after complete surgical resection of tumor
- Prior allogeneic stem-cell or solid-organ transplantation
- Recent or ongoing severe or clinically significant infection, including but
not limited to, hospitalization for complications of infection, bacteremia, or
severe pneumonia
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| ClinicalTrials.gov | NCT05419375 |
| CCMO | NL81892.000.22 |