Phase 3 study of SBRT ± pembrolizumab for participants with medically inoperable Stage I or IIA NSCLC

• Register: EUCTR
• Last refreshed on: 16 November 2020
• Main ID: EUCTR2018-004320-11-GB
• Date of registration: 08/11/2019
• Prospective Registration: No
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: Phase 3 study of SBRT ± pembrolizumab for participants with medically inoperable Stage I or IIA NSCLC
• Scientific title: A Phase 3, Randomized, Placebo-Controlled Clinical Study to Evaluate the Safety and Efficacy of Stereotactic Body Radiotherapy (SBRT) with or without Pembrolizumab (MK-3475) in Participants with Medically Inoperable Stages I or IIA Non Small Cell Lung Cancer (NSCLC) (KEYNOTE-867) - Pembrolizumab ± SBRT in Medically Inoperable Stage I/IIA NSCLC
• Date of first enrolment: 16/07/2019
• Target sample size: 530
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004320-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Brazil, Canada, France, Germany, Hungary, Italy, Japan, Korea, Republic of, New Zealand, Norway, Poland, Russian Federation, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Tayeb Naveed
• Affiliation: Merck Sharp & Dohme (UK) Ltd.

• Name: Tayeb Naveed
• Affiliation: Merck Sharp & Dohme (UK) Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
A participant will be eligible for inclusion in the study if the participant:
1. Has previosly untreated NSCLC diagnosed by histology or cytology and confirmed as Stage I or IIA NSCLC (AJCC 8th edition) by chest CT and PET scan. Prospective participants with mediastinal lymph nodes measured on chest CT as >1 cm in the short axis or PET avid lymph nodes may be eligible if the lymph node(s) in question is biopsied and is histologically benign.
2. Cannot undergo thoracic surgery due to existing medical illness(es) as determined by the site's multi-disciplinary tumor board. Participants, who are able to withstand thoracic surgery, but choose to pursue non-operative therapy, are not eligible. If there is no tumor board, then this decision will be made by the investigator in consultation with a thoracic surgeon and a radiation oncologist if the investigator is not a radiation oncologist.
3. Has an ECOG Performance Status of 0, 1, or 2.
4. Is able to receive SBRT and does not have an ultra-centrally located tumor as defined in the radiation manual.
5. Has adequate organ function. Specimens must be collected within 7 days prior to the start of study intervention.
6. Is male or female =18 years of age, at the time of signing the informed consent.
Male Participants
7. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Female Participants
8. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
9. A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) not a women of childbearing potential (WOCBP) OR b) A WOCBP who agrees to follow the contraceptive guidance during the treatment interval and for at least 120 days from the last dose of study treatment.
10. The participant (or legally acceptable representative if applicable) provides 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 biomedical research.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400

Exclusion criteria:
The participant must be excluded from the study if the participant:
1. Is a WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. 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 (e.g., CTLA-4, OX-40, CD137).
3. Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or breast. Participants receiving radiotherapy to the contralateral breast at least 5 years prior to randomization may still be eligible.
4. Has received a live vaccine within 30 days prior to the first dose of study 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.
5. 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.
6. 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 drug.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
8. Has a known hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
9. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
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 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). However, replacement therapy (eg thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency), while systemic, will be permitted for study eligibility.
12. Has an active infection requiring systemic therapy.
13. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
14. Has a known history of active tuberculosis (TB; Bacillus tuberculosis). No TB testing is required unless mandated by local health authority.
15. 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.
16. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
17. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non-Small Cell Lung Cancer Stage I or IIA
MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: KEYTRUDA®
Product Name: KEYTRUDA®
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): 1. Event-Free Survival (EFS)
2. Overall Survival (OS)

Main Objective: 1.To compare the Event Free Survival (EFS).
2.To compare Overall Survival (OS).

Secondary Objective: 1.To compare the time to death or distant metastases (TDDM).
2.To evaluate the safety and tolerability of Stereotactic Body Radiotherapy (SBRT) + pembrolizumab (MK-3475).
3.To compare the change from baseline scores in global health status/quality of life (QoL), cough, chest pain, dyspnea, and physical functioning scale.

Timepoint(s) of evaluation of this end point: 1. Up to approximately 6 years
2. Up to approximately 6 years

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Up to approximately 6 years
2. Up to approximately 6 years
3. Up to approximately 6 years
4. Baseline and up to approximately 52 weeks
5. Baseline and up to approximately 52 weeks
6. Baseline and up to approximately 52 weeks
7. Baseline and up to approximately 52 weeks
8. Baseline and up to approximately 52 weeks

Secondary end point(s): 1. Time to Death or Distant Metastases (TDDM)
2. Number of Participants Who Experience an Adverse Event (AE)
3. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
4. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Score
5. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module 13 (EORTC QLQ-LC13) Cough (Item 1) Score
6. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module 13 (EORTC QLQ-LC13) Chest Pain (Item 10) Score
7. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score
8. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score

Secondary ID(s)

2018-004320-11-HU

116.833

MK-3475-867

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Ethics review

Status: Approved
Approval date: 16/07/2019
Contact: