Phase 3 study of pembrolizumab SC versus pembrolizumab IV, administered with platinum doublet chemotherapy, in 1L metastatic squamous or nonsquamous NSCLC
- Conditions
- Metastatic Squamous or Nonsquamous Non-Small-Cell Lung CancerMedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002729-27-RO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 450
1. Has pathologically (histologically or cytologically) confirmed diagnosis of squamous or nonsquamous NSCLC
2. Has Stage IV (T any, N any, M1a, M1b, or M1c - American Joint Committee on Cancer 8th Edition) squamous or nonsquamous NSCLC
3. Has 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 KRAS mutation) in nonsquamous NSCLC as well as mixed nonsquamous/squamous NSCLC. Participants with purely squamous NSCLC do not require testing
4. Has not received prior systemic treatment for their 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
5. Participants are at least 18 years of age on the day of signing the informed consent
6. Has an ECOG PS of 0 or 1 (as assessed within 7 days prior to randomization)
7. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 95 days from the last dose of chemotherapy:
• Refrain from donating sperm
PLUS either:
• 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
• Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant
8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, 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 chemotherapy or 120 days after the last dose of pembrolizumab, whichever occurs last, and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this same time period 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
• A WOCBP must have a negative highly sensitive pregnancy test (as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test is positive or not evaluable, a serum test will be required
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
9. The participant (or legally acceptable representative) provides documented 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 biomedical research
10. Has measurable disease per RECIST 1.1 as assessed by the local
1. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
2. Has known central nervous system (ie, brain and/or spinal cord) metastases and/or carcinomatous meningitis. Participants with treated brain metastases (eg, whole brain radiation treatment [WBRT], stereotactic radiosurgery, or equivalent) may participate only if they satisfy all of the following:
• Have no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging (using the same modality) performed at least 4 weeks after pretreatment brain imaging, and
• Are neurologically stable without the need for steroids for at least 14 days before first dose of trial treatment as per local site assessment
3. Has severe hypersensitivity (=Grade 3) to study intervention and/or any of its excipients
4. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
5. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Lymphangitic spread of the NSCLC is not exclusionary
6. Has an active infection requiring systemic therapy
7. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority
8. 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
9. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
10. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
11. Has symptomatic ascites or pleural effusion. A participant who is clinically stable after treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible
12. Before the first dose of study intervention:
• Has received prior systemic cytotoxic chemotherapy for metastatic NSCLC
• Has received antineoplastic biological therapy (eg, erlotinib, crizotinib, cetuximab) for metastatic NSCLC
• Has had major surgery (<3 weeks prior to first dose)
• 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 coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
13. Received radiation therapy to the lung that is >30 Gray within 6 months of the first dose of study intervention
14. Is expected to require any other form of antineoplastic therapy while on study
15. Is unable to interrupt aspirin or other NSAIDs, other than an aspirin dose =1.3 g/day, for a 5-day period (8-day period for long acting agents, such as piroxicam)
16. Is unable or unwilling to take folic acid or vitamin B12 supplementation
17. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation related toxicities, not req
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method