Chemo +/- Pembrolizumab (MK-3475) as Perioperative Therapy for Stage II, IIIA-Resectable IIIB (N2) NSCLC

Phase 1

• Conditions: eoadjuvant/Adjuvant treatment for participants with Resectable Stage II or IIIA-B (N2) NSCLC; MedDRA version: 21.1Level: PTClassification code 10029518Term: Non-small cell lung cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10029520Term: Non-small cell lung cancer stage IIIASystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001832-21-LV
• 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: 2020-03-31
• Last Update Posted: 8 June 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 786

Inclusion Criteria

1. Male/female participants who are at least 18 years of age on the day of signing informed consent with previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) NSCLC. Lymph node disease requires pathologic confirmation, while T3 (rib destruction) disease requires only radiographic documentation. A PET scan may be utilized as a surrogate for pathologic staging of N1 lymph nodes for participants with T2b and T4 tumors (the presence or absence of tumor in the N1 lymph nodes will not change the actual stage by which the participant is stratified).
2. Be able to undergo protocol therapy, including necessary surgery.
3. A male participant must agree to use contraception, as detailed in protocol Appendix 3: Contraceptive Guidance and Pregnancy Testing) for at least 180 days, (corresponding to time needed to eliminate any study treatment(s) [pembrolizumab and or any active combination] plus an additional 90 days [a spermatogenesis cycle] for study treatments where there is risk of clinically relevant genotoxicity) after the last dose of study treatment and refrain from donating sperm during this period.
4. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
5. A female participant is eligible to participate if she is not pregnant (see protocol Appendix 3: Contraceptive Guidance and Pregnancy Testing), not breastfeeding, and at least one of the following conditions applies:
a.) Not a woman of childbearing potential (WOCBP) as defined in protocol Appendix 3: Contraceptive Guidance and Pregnancy Testing
OR
b.) A WOCBP who agrees to follow the contraceptive guidance in protocol Appendix 3: Contraceptive Guidance and Pregnancy Testing during the treatment period and for at least 180 days (corresponding to time needed to eliminate any study treatment(s) [pembrolizumab and or any active combination] plus 30 days [a menstruation cycle] for study treatments with risk of genotoxicity) after the last dose of study treatment.
6. The participant provides written informed consent/assent for the trial. The participant may also provide consent for Future Biomedical Research. However, the participant may participate in the study without participating in Future Biomedical Research.
7. Have available formalin-fixed paraffin embedded (FFPE) tumor tissue sample blocks for submission. If blocks are not available, have unstained slides for submission for central PD-L1 testing. See Procedures Manual for further details.
8. Have an ECOG performance status of 0 to 1 within 10 days of randomization.
9. Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of trial treatment.
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 260
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 526

Exclusion Criteria

1. A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment (see protocol Appendix 3). If the urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
2. Has one of the following tumor locations/types:
- NSCLC involving the superior sulcus
- Large cell neuro-endocrine cancer (LCNEC)
- Sarcomatoid tumor
3. Has a history of (non-infectious) pneumonitis /interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease that requires steroids.
4. Has an active infection requiring systemic therapy.
5. Has had an allogenic tissue/solid organ transplant.
6. Has a known severe hypersensitivity (= Grade 3) to pembrolizumab, its active substance and/or any of its excipients.
(Refer to the respective Investigator’sBrochure for a list of excipients.)
7. Has a known severe hypersensitivity (= Grade 3) to any of the study chemotherapy agents and/or to any of their excipients.
8. 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.
9. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
10. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
11. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant’s participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
15. Has received prior systemic anticancer therapy including investigational agents for the current malignancy prior to randomization/allocation.
16. Has received prior radiotherapy within 2 weeks of start of trial treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
17. Has received a live vaccine within 30 days prior to the first dose of trial drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
18. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device

Study & Design

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