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EUCTR2018-004320-11

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

Data source: WHO (Imported from 22.11.2020)
Changed: 22.11.2020
Disease category:

Health conditions (Data source: WHO)

Non-Small Cell Lung Cancer Stage I or IIA
MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04]

Interventions (Data source: WHO)


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

Inclusion/Exclusion Criteria (Data source: WHO)

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

Further information on the trial in WHO primary registry

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004320-11

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2018-004320-11-GB

Further information on trial

Date trial registered

08.11.2019

Incorporation of the first participant

16.07.2019

Recruitment status

Authorised-recruitment may be ongoing or finished

Academic title (Data source: WHO)

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

Type of trial (Data source: WHO)

Interventional clinical trial of medicinal product

Design of the trial (Data source: WHO)

Controlled: yesRandomised: yesOpen: noSingle blind: noDouble blind: yesParallel group: yesCross over: noOther: noIf controlled, specify comparator, Other Medicinial Product: noPlacebo: yesOther: noNumber of treatment arms in the trial: 2

Phase (Data source: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no

Primary end point (Data source: WHO)

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.;Primary end point(s): 1. Event-Free Survival (EFS)
2. Overall Survival (OS);Timepoint(s) of evaluation of this end point: 1. Up to approximately 6 years
2. Up to approximately 6 years

Secundary end point (Data source: WHO)

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;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

Contact information (Data source: WHO)

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

Trial results (Data source: WHO)

Results summary

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)

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Countries (Data source: WHO)

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

Contact for further information on the trial

Contact for general information (Data source: WHO)

Tayeb Naveed
2 Pancras Square, Kings Cross
Merck Sharp & Dohme (UK) Ltd.
01992 452519
tayeb.naveed@msd.com

Contact for scientific information (Data source: WHO)

Tayeb Naveed
2 Pancras Square, Kings Cross
Merck Sharp & Dohme (UK) Ltd.
01992 452519
tayeb.naveed@msd.com

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

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

Further trial identification numbers

Secondary ID (Data source: WHO)

MK-3475-867
116.833
2018-004320-11-HU