Phase 3 study of SBRT ± pembrolizumab for participants with unresectable Stage I or II NSCLC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Jun 2019 → 20 Jan 2025

Decision date (initial)

2023-02-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-500413-11-00

EudraCT number

2018-004320-11

WHO UTN

U1111-1275-8515

ClinicalTrials.gov

NCT03924869

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenomic, Pharmacoeconomic, Safety, Pharmacogenetic, Therapy

1. To compare the Event free Survival (EFS)

Secondary objectives 4

1. To compare Overall Survival (OS)
2. To evaluate the time to death or distant metastases
3. To evaluate the safety and tolerability of stereotactic body radiotherapy (SBRT) + pembrolizumab
4. To evaluate the change from baseline scores in global health status/quality of life (QoL), cough, chest pain, dyspnea, and physical functioning scale

Conditions and MedDRA coding

Unresected Stage I or II Non-Small Cell Lung Cancer (NSCLC)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Has previously untreated non-small cell lung cancer (NSCLC) diagnosed by histology or cytology and confirmed as Stage I or II (T1 to limited T3, N0, M0) NSCLC (American Joint Committee on Cancer, AJCC) by chest computed tomography (CT) and positron emission tomography (PET) scan. Participants with pericardium invasion, >2 nodules or 2 nodules that cannot be treated in one field (>2 cm apart and/or total planned target volume [PTV] >163 cc) and diaphragm elevation suggestive of phrenic nerve invasion are excluded
2. Cannot undergo thoracic surgery due to existing medical illness(es) as determined by the site’s multi-disciplinary tumor board. Medically operable participants who decide to treat with stereotactic body radiotherapy (SBRT) as definitive therapy rather than surgery are also eligible, if patient’s unwillingness to undergo surgical resection is clearly documented
3. Has a Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
4. Is able to receive SBRT and does not have an ultra-centrally located tumor
5. Has adequate organ function within 7 days prior to the start of study treatmet
6. 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 and uses contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least 120 days after the last dose of pembrolizumab/placebo and 180 days after the last radiotherapy dose
7. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of radiotherapy: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use contraception per study protocol, unless confirmed to be azoospermic
8. Has a radiation therapy plan approved by the central radiation therapy quality assurance vendor

Exclusion criteria 16

1. Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 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. cytotoxic T-lymphocyte–associated antigen 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], tumor necrosis factor receptor superfamily member 9 [CD137])
2. Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or breast
3. Has received a live vaccine within 30 days prior to the first dose of study intervention
4. Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention administration
5. 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 treatment
6. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. A prior NSCLC that occurred and was treated curatively at least 2 years prior to the date of the current diagnosis would be considered a separate primary lung cancer, and therefore an additional malignancy. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast c carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
7. Has a known hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
8. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
9. Has a known history of Hepatitis B or known active Hepatitis C virus infection
10. Has an active autoimmune disease that has required systemic treatment in past 2 years, except replacement therapy
11. Has an active infection requiring systemic therapy
12. Has a known history of human immunodeficiency virus (HIV) infection
13. Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
14. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab/placebo and 180 days after the last radiotherapy dose
15. Have not adequately recovered from major surgery or have ongoing surgical complications
16. Has had an allogenic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event-Free Survival (EFS)

Secondary endpoints 9

1. Overall Survival (OS)
2. Time to Death or Distant Metastases (TDDM)
3. Number of Participants Who Experience an Adverse Event (AE)
4. Number of Participants Who Discontinue Study Treatment Due to an AE
5. 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
6. 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
7. 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
8. 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
9. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme Corp.

Sponsor organisation

Merck Sharp & Dohme Corp.

Address

1 Merck Drive, PO Box 100 PO Box 100

City

Whitehouse Station

Postcode

08889-3400

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme Corp.

Contact name

Andrew Song

Public contact point

Organisation

Merck Sharp & Dohme Corp.

Contact name

Andrew Song

Third parties 6

Locations

10 EU/EEA countries · 48 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications