PHASE 3 STUDY OF PEMBROLIZUMAB WITH CONCURRENT CHEMORADIATION THERAPY FOLLOWED BY PEMBROLIZUMAB WITH OR WITHOUT OLAPARIB COMPARED TO CONCURRENT CHEMORADIATION THERAPY FOLLOWED BY DURVALUMAB IN STAGE III NSCLC
- Conditions
- -C34 Malignant neoplasm of bronchus and lungMalignant neoplasm of bronchus and lungC34
- Registration Number
- PER-024-20
- Lead Sponsor
- Merck Sharp & Dohme Corp., una subsidiaria de Merck & Co. Inc.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 14
1. Has pathologically confirmed NSCLC.
2. Has Stage IIIA, IIIB, or IIIC NSCLC
3. Is unable to undergo surgery with curative intent for Stage III NSCLC
4. Has no evidence of metastatic disease, indicating Stage IV NSCLC, in whole-body fluorodeoxyglucose (FDG)-PET or FDG-PET/CT and CT or MRI scans of diagnostic quality of chest, abdomen, pelvis and brain.
5. Has measurable disease as defined by RECIST 1.1, with at least one lesion being appropriate for selection as a target lesion,.
6. Has not received prior treatment for their Stage III NSCLC.
7. Has provided tumor tissue sample
8. Has a performance status of 0 or 1 on the ECOG Performance Status assessed within 7 days prior to the first administration of study intervention.
9. Has a life expectancy of at least 6 months
10. Has adequate PFT defined as a FEV1 >50% of predicted normal volume and the carbon monoxide lung diffusing capacity (DLCO) >40% of predicted normal value.
11. Has adequate organ function as defined in Table 1; all screening laboratory tests should be performed within 10 days prior to initiation of study intervention.
12. Is male or female of at least 18 years to 120 years of age inclusive, at the time of signing the informed consent.
13. A male participant must agree to use contraception as detailed in Appendix 4 of this protocol during the treatment period and for at least 180 days following the last dose of study intervention.
14. A female participant is eligible to participate if she is not pregnant (Appendix 4), not breastfeeding, and at least 1 of the following conditions applies:
a. Not a WOCBP as defined in Appendix 4.
OR
b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the treatment period and for at least 180 days following the last dose of study intervention.
Please refer to the protocol for more information
1. Has small cell lung cancer or a mixed tumor with presence of small cell elements.
2. Has history, current diagnosis, or features suggestive of MDS/AML.
3. Has had documented weight loss >10% (from baseline) in the preceding 3 months.
4. Has a radiation treatment plan that is likely to encompass a volume of whole lung (total lung V20-GTV) receiving > 20 Gy in total (V20) of more than 34% of lung volume.
5. Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or for breast cancer.
6. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX- 40, CD137).
7. Has received prior therapy with olaparib or with any other PARP inhibitor.
8. Has received a live vaccine within 30 days prior to the first dose of study medication.
9. Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [GCSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 28 days prior to the first dose of study intervention.
10. Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study.
11. Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study.
12. Is unable to interrupt aspirin or other NSAIDs, other than an aspirin dose ≤1.3 grams per day, for at least 2 days (5 days for long-acting agents [for example, piroxicam]) before, during, and for at least 2 days after administration of pemetrexed.
13. Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone.
14 Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
15. Has resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, electrolyte disturbances, etc.), or participant has congenital long QT syndrome.
16. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
17. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
18. Has severe hypersensitivity (≥ Grade 3) to study intervention and/or any of its excipients
19. Has an active autoimmune disease that has required systemic treatment in past 2 years
20. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
21. Has an active infection requiring systemic therapy.
22. Has a known history of human immunodeficiency virus (HIV) infection.
23. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active
Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
24. Has active tuberculosis (TB; Mycobacterium tuberculosis) and is receiving treatment
25. Is unable to swallow orally administered medication or has a gastroi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Kaplan Meier Method<br>Measure:Progression-free survival (PFS)<br>Timepoints:The interim analysis will be conducted around 38 months after the first participant is randomized. The final analysis will be conducted around 48 months after the first<br>participant is randomized.<br>;<br>Outcome name:Kaplan Meier Method<br>Measure:Overall survival (OS)<br>Timepoints:The analysis will be conducted around 38, 48 and 57 months after the first participant is randomized. The final analysis will be conducted around 72 months after the first<br>participant is randomized<br>
- Secondary Outcome Measures
Name Time Method