To compare the objective response rate between patients with metastatic non-small cell lung cancer characterized by PDL-1 TPS
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Objective response rate
Secondary outcome
Clinical benefit rate (defined as the proportion of patients with CR/PR + SD),
progression free survival (PFS), overall survival (OS)
Background summary
Biomarkers beyond PD-L1 to identify patients with metastatic non-small cell
lung cancer that will not derive benefit from treatment with immune checkpoint
inhibition are currently lacking. In a retrospective study we uncovered a
complex biomarker consisting of low cTML and either STK11, KEAP1 or oncogenic
driver mutation that independent of PD-L1 predicted for non response following
treatment with single agent immune checkpoint inhibition. Here we propose to
validate this biomarker prospectively.
Study objective
To compare the objective response rate between patients with metastatic
non-small cell lung cancer characterized by PDL-1 TPS<50% and low cTML (<300
nonsynonymous mutations) and either actionable mutation, inactivating STK11 or
KEAP1 mutations, treated by either chemo-immunotherapy or chemotherapy alone.
Study design
Randomized controlled phase II clinical study
Intervention
Patients will receive carboplatin-pemetrexed-pembrolizumab according to the
KN189 regimen or the same dose and schedule of carboplatin-pemetrexed
Study burden and risks
The determination of the biomarker to be validated requires an extension of a
standard molecular diagnostic laboratory procedure, i.e. is not associated with
any risk for the patient. Both carboplatin-pemetrexed-pembrolizumab and
carboplatin-pembrolizumab are standard of care regimen whose risk-benefit ratio
is well characterized and established. No additional procedures compared to
routine management of patients with advanced non small cell lung cancer
undergoing systemic treatment will be implemented
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
1. Age >18 years 2. Advanced, metastatic non-small cell lung cancer UICC stage
IV 3. ECOG PS 0-2 4. PDL-1 TPS <50% (Dako 22C3) 5. Low cTML (<300 nonsynonymous
mutations) and either actionable mutation, inactivating STK11 or KEAP1
mutations as detected by NGS using OCA+ or TSO500 gene panel. 6. No prior
systemic therapy except for patients with activating mutations. 7. Fit for
treatment with chemo-immunotherapy deemed by the treating physician. 8.
Measurable disease (RECIST 1.1). 9. In case of activating mutation,
pretreatment with appropriate (i.e. guideline recommended) targeted therapy is
required with demonstrated disease progression.
Exclusion criteria
1. Symptomatic CNS metastasis requiring immediate radiotherapy or neurosurgical
intervention.
2. Any contra-indication (as per label) for treatment with immune checkpoint
inhibitors.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 | NL82961.000.23 |