The objective of the diagnostic performance study is to determine the KRAS G12C status in tissues of NSCLC tumors collected from potential study subjects, in order to determine their biomarker eligibility for study BO45217. Currently, there is no…
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Brief title
Condition
- Respiratory tract neoplasms
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Research involving
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Intervention
Outcome measures
Primary outcome
The objective of the diagnostic performance study is to determine KRAS G12C
status in tissues of NSCLC tumors collected from potential study
subjects to determine their biomarker eligibility for study BO45217. Currently,
there is no plan for the therascreen® KRAS RGQ PCR Kit to
be further developed as a companion diagnostic based on the results of study
BO45217. As such, there are no separate, independent endpoints
specified to be evaluated for the use of the assay in the clinical performance
study beyond the BO45217 trial objectives evaluating the
clinical safety and efficacy of the biomarker-selected treatments.
Secondary outcome
NA
Background summary
The scientific validity for the use of the therascreen® KRAS RGQ PCR Kit is
based on the rationale for use of the KRAS G12C biomarker. Lung cancer is the
leading cause of cancer death in the world (Sung et al. 2021). Standard first
line treatment for NSCLC (including KRAS G12C+) includes
platinum-based chemotherapy, immunotherapy, or a combination of chemotherapy
and immunotherapy. NSCLC that has been treated with standard of care
chemotherapy and/or immunotherapy has a poor prognosis. Divarasib (also known
as GDC-6036) is an oral, covalent, anti-cancer therapeutic agent that
selectively inhibits KRAS G12C but not wild-type or other mutations of KRAS or
other members of the RAS family. Because NSCLC is a heterogeneous disease, all
participants may not equally benefit from treatment with KRAS G12C inhibitors,
including divarasib. Tissue samples will be assessed for predictive biomarkers
in an effort to identify those participants with KRAS G12C-positive tumors who
are most likely to respond to treatment with KRAS G12C inhibitors, including
divarasib. The therascreen® KRAS RGQ PCR Kit will be used to determine
biomarker eligibility (KRAS G12C positive mutation status) in prospective
participants with advanced or metastatic NSCLC who do not have pre-existing
KRAS G12C results.
Study objective
The objective of the diagnostic performance study is to determine the KRAS G12C
status in tissues of NSCLC tumors collected from potential study subjects, in
order to determine their biomarker eligibility for study BO45217. Currently,
there is no plan to further develop the therascreen® KRAS RGQ PCR Kit as a
companion diagnostic based on the results of study BO45217. Therefore, there
are no separate, independent endpoints specified to evaluate the use of the
assay in the diagnostic performance study, apart from the objectives of the
BO45217 trial evaluating the clinical safety and efficacy of the
biomarker-selected treatments.
Study design
The clinical performance study (CPS) supports clinical study BO45217 by
describing the procedures for how patient tumor samples collected as part of
study BO45217 will be tested to determine KRAS G12C biomarker eligibility. The
therascreen® KRAS RGQ PCR Kit will be used to determine biomarker eligibility
(KRAS G12C positive mutation status) in prospective participants with advanced
or metastatic NSCLC who do not have pre-existing KRAS G12C results. In this
study, archival or fresh NSCLC tumor tissue samples from all potential
participants will be submitted to a central laboratory. Tumor specimens
submitted for a potentially eligible patient that does not have a pre-existing
result available will be prospectively tested for the KRAS G12C mutation at the
central testing sites, using the therascreen® KRAS RGQ PCR kit. Eligible
participants will be randomized 1:1 to
receive either divarasib (experimental arm) or a locally approved KRAS G12C
inhibitor (sotorasib or adagrasib) (control arm). This performance study is
being carried out in accordance with Article 58 of the In Vitro Diagnostics
Regulation.
Intervention
Intervention in the BO4217 study includes the following treatments:
Divarasib
Sotorasib
Adagrasib
Study burden and risks
Please see section 4. Risks and Benefits of Device and Clinical Performance
Study in the CPSP (page 23
Beneluxlaan 2A
Woerden 3446AA
NL
Beneluxlaan 2A
Woerden 3446AA
NL
Listed location countries
Age
Inclusion criteria
Tissue inclusion / exclusion criteria: Tumor specimens will be formalin-fixed,
paraffin-embedded (FFPE) in a paraffin block (preferred) or 10-15 (15
preferred) unstained, freshly cut, serial slides and should be of good quality,
with a minimum of 500 viable tumor cells. Samples collected via resection, core
needle biopsy, excisional, incisional, punch, or forceps biopsy, or
endobronchial ultrasound (EBUS)-transbronchial needle aspiration are
acceptable. Samples that do not preserve tissue architecture, including
fine-needle aspiration, brushing, cell pellets from pleural effusion, and
lavage samples are not acceptable. Tumor tissue from bone metastases that have
been decalcified is not acceptable.
Details on the inclusion criteria of the study subjects are described in
Section 5.1 of the clinical trial protocol for BO45217
Exclusion criteria
Details on the exclusion criteria of the study subjects are described in
Section 5.1 of the clinical trial protocol for BO45217
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 |
|---|---|
| CCMO | NL86869.000.24 |