Phase 3 Study of Pembrolizumab with Maintenance Olaparib or Maintenance Pemetrexed in 1L Metastatic Nonsquamous NSCLC

Phase 1

• Conditions: MedDRA version: 20.0 Level: LLT Classification code 10079440 Term: Non-squamous non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Stage IV lung cancer condition; MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2018-004720-11-GB
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-16
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 535

Inclusion Criteria

1. Have a histologically confirmed or cytologically confirmed diagnosis of nonsquamous NSCLC.
2. Have Stage IV (T any, N any, M1a, M1b, or M1c - American Joint Committee on Cancer (AJCC) 8th Edition) nonsquamous NSCLC.
3. Have confirmation that EGFR, ALK, or ROS1-directed therapy is not indicated (documentation of absence of tumor-activating EGFR mutations AND absence of ALK and ROS1 gene rearrangements, OR presence of a K-Ras mutation).
4. Have measurable disease, based on RECIST 1.1, as determined by the local site investigator/radiology assessment. Lesions that appear measurable, but are situated in a previously irradiated area, can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation.
5. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
6. Have a life expectancy of at least 3 months.
7. Have an ECOG performance score of 0 or 1 assessed within 7 days prior to the administration of study intervention.
8. Have not received prior systemic treatment for their advanced/metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease.
9. Have adequate organ function. All screening laboratory tests should be performed within 10 days prior to the first dose of study intervention.
10. Be at least 18 years of age at the time of signing the informed consent.
11. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 180 days after the last dose of study intervention:
- Refrain from donating sperm
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent
OR
- Agree to use contraception, unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
12. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
a) Is not a WOCBP
OR
b) Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
13. Have (or legally acceptable representative if applicable) provided written informed consent/assent for the study. The participant may also provide consent/assent for future biomedical research. However, the participant may participate in the main study without participating in future

Exclusion Criteria

1. Has predominantly squamous cell histology NSCLC.
2. Has a known additional malignancy that is progressing or has progressed within the past 3 years requiring active treatment.
3. Has known active central nervous system metastases and/or carcinomatous meningitis.
4. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
5. Participant has a known hypersensitivity to any components or excipients of cisplatin, carboplatin, pemetrexed, or olaparib.
6. Has active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment and is allowed.
7. 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 intervention.
8. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
9. Has an active infection requiring systemic therapy.
10. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required, unless mandated by local health authority.
11. Has a known history of hepatitis B or known active hepatitis C virus infection.
12. Has a known history of active tuberculosis.
13. Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
14. Has a known history of interstitial lung disease. Lymphangitic spread of the NSCLC is not exclusionary.
15. Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
16. Before the first dose of study intervention:
a. Has received prior systemic cytotoxic chemotherapy for metastatic disease.
b. Has received antineoplastic biological therapy (eg, erlotinib, crizotinib, cetuximab) for metastatic disease.
c. Had major surgery (<3 weeks prior to study intervention) or has not recovered from any effects of any major surgery.
17. Has received prior therapy with olaparib or with any other PARP inhibitor.
18. Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study intervention.
19. Is expected to require any other form of antineoplastic therapy while on study.
20. 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).
21. Has received a live vaccine within 30 days prior to the first dose of study drug.
22. Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs, other than an aspirin dose =1.3 g per day, for a 5-day period (an 8-day period for long-acting agents, such as piroxicam).
23. Is unable or unwilling to take folic acid or vitamin B12 supplementation.
24. Received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified