Phase 3 1L Study of Pembrolizumab ± Ipilimumab in NSCLC

Phase 1

• Conditions: Metastatic programmed cell deathligand 1 (PD-L1) positive (TPS =50%) non-small cell lung cancer (NSCLC); MedDRA version: 20.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004364-20-FR
• 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: 2017-12-05
• Study Completion: 2022-09-07
• Last Update Posted: 15 January 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 568

Inclusion Criteria

1. Be willing and able to provide written informed consent for the trial. The subject may also provide consent/assent for future biomedical research (FBR); however, the subject may participate in the main trial without participating in FBR.
2. Be at least 18 years of age on the day of signing informed consent.
3. Have a histologically or cytologically confirmed diagnosis of Stage IV metastatic NSCLC (AJCC version 8).
4. Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesion.
5. Have a life expectancy of at least 3 months.
6. Have an ECOG Performance Status of 0 or 1.
7. Have adequate organ function as indicated in the protocol.
8. 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. Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut (details pertaining to tumor tissue submission can be found in the Procedures Manual). Tumor demonstrates PD-L1 expression in =50% of tumor cells (TPS = 50%) as assessed by IHC at a central laboratory.
9. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
10. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in protocol Section 5.7.2 – Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
11. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in protocol Section 5.7.2 – Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 301
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 247

Exclusion Criteria

1. Has received prior systemic chemotherapy/other targeted or biological antineoplastic therapy treatment for their Stage IV metastatic NSCLC.
2. Tumor harbors an EGFR-sensitizing (activating) mutation or an ALK translocation.
3. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
4. 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).
5. Has received prior radiotherapy within 2 weeks of start of trial treatment or received lung radiation therapy of >30 Gy within 6 months of the first dose of trial treatment. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.
6. The subject’s NSCLC can be treated with curative intent with surgical resection, localized radiotherapy, or chemoradiation.
7. Tumor specimen is not evaluable for PD-L1 expression.
8. Is receiving systemic steroid therapy =7 days prior to the first dose of trial treatment or receiving any other form of immunosuppressive medication.
a) Corticosteroid use on study after Cycle 1 for management of AEs, SAEs, and events of clinical interest (ECIs), as a pre-medication for IV contrast allergies/reactions or if considered necessary for a subject’s welfare, is allowed.
b) Subjects who receive daily steroid replacement therapy serve as an exception to this rule. Daily prednisone at doses of 5 to 7.5 mg (or hydrocortisone equivalent doses) is an example of replacement therapy.
c) Subjects who use inhaled steroids for the control of asthma serve as an exception to this rule.
9. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
10. Has known untreated-CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression for at least 4 weeks by repeat imaging [note that the repeat imaging should be performed during study screening]), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of trial treatment.
11. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
12. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (i.e., doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.
13. Has a history of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
14. Has had an allogeneic tissue/solid organ transplant.
15. Has received a live vaccine within 30 days prior to the first dose of trial treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoste

Study & Design

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