Einleitung wieder einblenden
EUCTR2015-000575-27

Immunotherapeutic treatment with Pembrolizumab (antibody) in patients with early stage non-small cell lung cancer

Datenbasis: WHO (Import vom 27.09.2020)
Geändert: 13.09.2020
Krankheitskategorie:

Health conditions (Datenquelle: WHO)

Stage IB (T = 4 cm), II and IIIA NSCLC
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 (Datenquelle: WHO)


Product Name: pembrolizumab
Product Code: MK-3475; SCH900475
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive name: Anti-PD-1 monoclonal antibody
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Keytruda®
Product Name: pembrolizumab
Product Code: MK-3475; SCH900475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive name: Anti-PD-1 monoclonal antibody
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Inclusion criteria:
- Before patient registration, written informed consent for tumor testing must be given according to ICH/GCP and national/local regulations. For patients that accept to participate in the translational research, we recommend the informed consent for translational research be signed before registration step 1;
- Pathological diagnosis of NSCLC confirmed at surgery, any histology is eligible;
- Confirmed UICC v7 stage IB with T = 4 cm, II-IIIA NSCLC after complete surgical resection (lobectomy, sleeve lobectomy, bi-lobectomy or pneumonectomy) as documented in the pathology report;
- Resection margins proved microscopically free (R0); Resection margins are evaluated at the bronchial, venous and arterial stumps, peribronchial soft tissue, any peripheral margin near the tumor or of additionally resected tissue;
- A systematic complete mediastinal lymph node dissection or a lobespecific mediastinal lymph node dissection (Appendix K) is recommended. At a minimum, the pathology and/or operative report must include the examination of at least two different mediastinal lymph node (N2) levels, one of which is the subcarinal (level 7) and the second of which is lobe-specific;
- In the uncommon clinical situation where the surgeon thoroughly examines a particular mediastinal lymph node level and does not find any lymph nodes, that mediasintal lymph node level may be counted among the minimum two required levels. However, the surgeon must clearly document in the operative report or in a separate written statement that the lymph node level was explored and no lymph nodes were present. Normal appearing lymph nodes, if present, must be biopsied or/removed;
- No extracapsular nodal extension of the tumor in resected mediastinal (N2) lymph nodes. Extracapsular tumor extension is permitted in resected N1 lymph nodes;
- The highest mediastinal node removed can be positive for malignancy;
- Carcinoma in situ can be present at bronchial margin
- Availability of tumor sample obtained at surgical resection for PD-L1 Immunohistochemistry (IHC) expression assessment.
- At least 18 years;
- Adjuvant chemotherapy is not mandatory but considered for patients with stage IB (T = 4 cm) and strongly recommended for stage II and IIIA, and will be administered according to national and local guidelines. Patients who received more than 4 cycles of adjuvant therapy are not eligible;
- Patients not receiving adjuvant chemotherapy must be randomized and dosed with pembrolizumab/placebo within 12 weeks of their surgery date;
- Participants who receive adjuvant chemotherapy must begin adjuvant chemotherapy within 12 weeks of the surgery date. Patients receiving adjuvant chemotherapy must be randomized and dosed with pembrolizumab/placebo at least 3 weeks but no more than 12 weeks from the last dose of chemotherapy (Day 1 of last cycle);
- ECOG Performance status 0-1;
- Adequate organ function performed within 10 days of treatment initiation;
- Female patients with childbearing potential must have a negative urine or serum pregnancy test at screening (within 72 hours of first infusion of study medication)
- If of childbearing potential, female patients must be willing to use two adequate barrier methods throughout the study, starting with the screening visit up to 120 days after last infusion of chemotherapeutic and investigational agents as specified in the protocol;
- Male patients with a female partner(s) of child-bearing potential must agree to use two
Exclusion criteria:
- Evidence of disease at clinical examination and/or baseline radiological assessment on baseline assessment as documented by contrast enhanced chest/upper abdomen CT scan, brain CT/MRI and clinical examination within 8 weeks prior to the randomization date;
- Prior or planned neoadjuvant or adjuvant radiotherapy and/or neoadjuvant chemotherapy for the current malignancy;
- Prior treatment with an anti-PD-1, anti-PD-L1/2, anti- CD137, CTLA-4 modulators or any other immune-modulating agents; patients receiving live vaccine within 30 days prior to the first infusion of study treatment are not eligible;
- Current participation in a interventional clinical trial or treatment with an investigational agent or use of an investigational device within 4 weeks of the first infusion of study treatment;
- Known history of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodies positive). Known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg results. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay;
- Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in the last 3 days prior to the first infusion of trial treatment;
- History of interstitial lung disease (ILD) OR a history of (noninfectious) pneumonitis that required oral or IV steroids (other than COPD exacerbation) or current pneumonitis;
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Any replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment and is allowed. Patients with hyperthyroidism or hypothyroidism but that are stable on hormone replacement are also allowed
- History of a hematologic or primary solid tumor malignancy, unless in remission for at least 5 years. A pT1-2 prostatic cancer Gleason score < 6, superficial bladder cancer, non melanomatous skin cancer or carcinoma in situ of the cervix is eligible. Note: prior radiotherapy for another malignancy (breast cancer / lymphoma/germ cell tumors, etc.) is not an exclusion criterion, the same applies for prior anti-cancer systemic chemotherapy;
- Previous allogeneic tissue/solid organ transplant;
- Active infection requiring therapy;
- Surgery or chemotherapy related toxicity ( non-hematological, toxicity resolved to grade 1 (see Appendix D), with the exception of alopecia, fatigue, neuropathy and lack of appetite /nausea);
- Patients with two synchronous primary non-small cell lung cancers.

Weitere Angaben zur Studie im WHO-Primärregister

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000575-27

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2015-000575-27-SI

Weitere Informationen zur Studie

Registrationsdatum der Studie

15.07.2015

Einschluss der ersten teilnehmenden Person

21.09.2015

Rekrutierungsstatus

Authorised-recruitment may be ongoing or finished

Wissenschaftlicher Titel (Datenquelle: WHO)

A randomized, phase 3 trial with anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) versus placebo for patients with early stage NSCLC after resection and completion of standard adjuvant therapy (PEARLS) - PEARLS

Studientyp (Datenquelle: WHO)

Interventional clinical trial of medicinal product

Design der Studie (Datenquelle: 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 (Datenquelle: WHO)

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

Primäre Endpunkte (Datenquelle: WHO)

Main Objective: To prospectively investigate whether adjuvant treatment with pembrolizumab after completion of radical surgery (lobectomy/pneumonectomy) with or without standard adjuvant chemotherapy for stage IB (T = 4 cm) -II-IIIA NSCLC patients improves Disease Free Survival (DFS), as assessed locally by the investigator, compared to placebo in the PD-L1 strong positive subgroup (TPS=50%) or overall population.

Note: TNM stage (according to the 7th edition of the TNM classification for lung cancer).;Secondary Objective: - To prospectively compare DFS as assessed by the investigator in the PD-L1 positive population (TPS=1%);
- To prospectively determine and compare OS in the PD-L1 strong positive and overall population;
- To prospectively determine and compare OS in the PD-L1 positive population;
- To prospectively determine and evaluate the Lung Cancer Specific Survival (LCSS) in the whole population irrespective of PD-L1 status;
- To prospectively assess the safety of pembrolizumab after radical surgery followed by standard adjuvant chemotherapy.;Primary end point(s): 1. DFS in the PD-L1 strong positive sub-group;
2. DFS in the overall population (co-primary endpoint).
;Timepoint(s) of evaluation of this end point: 1. Every 12 weeks (± 2 weeks) during the 1st year after randomization, every 6 months for the 2nd and 3rd year, yearly up to the end of the 5th year
2. Every 12 weeks (± 2 weeks) during the 1st year after randomization, every 6 months for the 2nd and 3rd year, yearly up to the end of the 5th year

Sekundäre Endpunkte (Datenquelle: WHO)

Secondary end point(s): 1. DFS in the PD-L1 positive population;
2. OS in the overall population;
3. OS in the PD-L1 strong positive subgroup;
4. OS in the PD-L1 positive population;
5. LCSS in the overall population;
6. Toxicity according to CTCAE version 4.03.
;Timepoint(s) of evaluation of this end point: 1. Every 12 weeks (± 2 weeks) during the 1st year after randomization, every 6 months for the 2nd and 3rd year, yearly up to the end of the 5th year
2. OS will be measured from the date of randomization until the date of death.
3. OS will be measured from the date of randomization until the date of death.
4. OS will be measured from the date of randomization until the date of death.
5. LCSS will be measured from the date of randomization until the date of death (due to lung cancer specifically)
6. Every 3 weeks during treatment and at 12 weeks after the last treatment

Kontakt für Auskünfte (Datenquelle: WHO)

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

Ergebnisse der Studie (Datenquelle: WHO)

Zusammenfassung der Ergebnisse

A randomized, phase 3 trial with anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) versus placebo for patients with early stage NSCLC after resection and completion of standard adjuvant therapy (PEARLS)

Link zu den Ergebnissen im Primärregister

noch keine Angaben verfügbar

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten

noch keine Angaben verfügbar

Studiendurchführungsorte

Durchführungsländer (Datenquelle: WHO)

Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Latvia, Netherlands, Poland, Portugal, Republic of, Russian Federation, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom

Kontakt für weitere Auskünfte zur Studie

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

Global Clinical Trials Operations
One Merck Drive
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
+1267 305 3326
bilal.piperdi@merck.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Global Clinical Trials Operations
One Merck Drive
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
+1267 305 3326
bilal.piperdi@merck.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

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

Weitere Studienidentifikationsnummern

Secondary ID (Datenquelle: WHO)

MK-3475-091-03
1416-LCG
2015-000575-27-IE