Lung Cancer Non-Small Cell Lung Cancer
Conditions
Interventions
None listed
Sponsors
QIAGEN
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed NSCLC with Stage IIIB-IIIC or Stage IV disease, not suitable for curative intent radical surgery or radiation therapy. Staging will be according to the AJCC Staging System (8th ed [AJCC Cancer Staging Manual 8th Edition. 2020]). a. Part B and Safety Lead-In Part B: the histology of the tumor must be predominantly non-squamous (in line with pemetrexed label). 2. Must have disease with evidence of KRAS G12C mutation in tumor or blood sample as determined by molecular testing performed in a CLIA, ISO/IEC, CAP, or other similarly certified laboratory as per local guidelines including, but not limited, to IVDR compliance as applicable. 3. Must have known PD-L1 expression (estimated percentage [0%-100%] of tumor cells (TCs) showing partial or complete membranous PD-L1 staining) as determined by an IHC assay in a CLIA, ISO/IEC, CAP, or other similarly certified laboratory as per local guidelines including, but not limited to, IVDR compliance as applicable. a. Dose Optimization: 0% to 100% • Participants should be suitable as per the local label for first line treatment with pembrolizumab monotherapy in order to be eligible b. Safety Lead-In Part B: 0% to 100% c. Part A: >=50%. i. Participants with PD-L1 >=50% should be suitable for first line treatment with pembrolizumab monotherapy in order to be eligible (at the discretion of the investigator) d. Part B: 0% to 100%. 4. Must have measurable disease per RECIST v1.1 (Eisenhauer et al. 2009) as assessed by the investigator. Target lesions situated in a previously irradiated area are considered measurable if progression subsequent to radiation has been shown in such lesions, and the location of previously irradiated lesions is clearly documented. 5. Must have an ECOG performance status of 0 or 1 (Oken et al. 1982) 6. Estimated life expectancy >=12 weeks. 7. Ability to swallow capsules. 8. Must have adequate laboratory parameters, specimens must be collected within 14 days before the start of study intervention. 9. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 10. Women of childbearing potential must a. Have a negative pregnancy test (serum preferable) at screening, followed by a negative serum or urine result 24 hours prior to treatment with study intervention. b. Not be breastfeeding during treatment and after study intervention for at least 180 days. 11. Are capable of demonstrating an understanding of the nature, significance, and implications of participation in the trial and giving signed informed consent. 12. Are of an acceptable age to provide informed consent according to local regulations and are at least 18 years of age.
Exclusion criteria
Exclusion criteria: 1. Have a documented additional validated targetable oncogenic driver mutation or alteration in genes such as EGFR, ALK, BRAF (V600E), HER2, MET (exon 14), ROS1, RET, or NTRK1/2/3. 2. Have known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated CNS metastases may participate provided a. Any previous local treatment to treat CNS metastases must be completed at least 14 days prior to treatment Glucocorticoid therapy ((prednisone =14 days by repeat imaging). Patients must be neurologically and clinically stable for >=14 days prior to enrollment or randomization. Glucocorticoid therapy (equivalent of 10 mg/day of prednisone) at time of enrollment or randomization will be allowed Prophylactic anticonvulsants are permitted, provided the participant is on a stable dose for >=14 days prior enrollment or randomization. c. Participants with asymptomatic brain metastases (that is, no acute neurological symptoms requiring urgent CNS-directed therapy (radiation or surgery), no requirements for corticosteroids, and no lesion >1.5 cm) may participate. All patients with CNS metastases at baseline (asymptomatic or previously treated) will require regular imaging of the brain as a site of disease. 3. Have clinically significant active cardiovascular disease or history of myocardial infarction or unstable angina within 6 months prior to planned start of study. 4. Have prolongation of the QT interval corrected for heart rate using Fridericia*s formula (QTcF) >470 msec. If QTcF >470 msec on more than 1 ECG is obtained during the screening repeat 2 additional times and use the average to determine eligibility. Note that participants with implanted pacemakers may enter study without meeting QTc criteria due to nonevaluable measurement. 5. Have uncontrolled, disease-related, pericardial effusion or pleural effusion. 6. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current clinical significant pneumonitis/interstitial lung disease. 7. Have an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 8. History of allogenic tissue/solid organ transplant or allogenic stem cell transplant. 9. Have an active fungal, bacterial, and/or active untreated viral infection, including HIV or viral (A, B, or C) hepatitis (screening is not required unless mandated by local health authority). • HIV-infected participants must be on ART and have a well-controlled HIV infection/disease defined as: i. Participants on ART must have a CD4+ T-cell count >350 cells/mm3 at time of Screening ii. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Performance study endpoint is to demonstrate that the therascreen KRAS RGQ PCR Kit is safe and effective to identify patients for LY3537982 treatment, as supported by the efficacy and safety endpoints from the LY3537982 clinical trial JZQB/SUNRAY-01. | — |
Secondary
| Measure | Time frame |
|---|---|
| Nor applicable. | — |
Countries
Netherlands
Outcome results
None listed