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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Mar 2018 → ongoing

Decision date (initial)

2023-10-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-504820-24-00

EudraCT number

2017-001832-21

WHO UTN

U1111-1289-8426

ClinicalTrials.gov

NCT03425643

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacogenetic, Safety, Efficacy, Pharmacogenomic

1. To evaluate event-free survival (EFS) by biopsy assessed by a local pathologist or by investigator-assessed imaging using RECIST 1.1.
2. To evaluate the overall survival (OS).

Secondary objectives 4

1. To evaluate the rate of major pathological response (mPR) assessed by blinded central laboratory pathologist following NAC +/- pembrolizumab.
2. To evaluate the rate of pathological complete response (pCR) in the resected primary tumor and lymph nodes assessed by blinded central laboratory pathologist following NAC +/- pembrolizumab.
3. To evaluate mean change from baseline in the neoadjuvant phase and in the adjuvant phase in global health status/quality of life (QoL) using the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire (QLQ)-C30.
4. To evaluate the safety and tolerability of NAC plus pembrolizumab followed by surgery and adjuvant pembrolizumab.

Conditions and MedDRA coding

Neoadjuvant/Adjuvant treatment for participants with Resectable Stage II or IIIA-B (N2) 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 6

1. Have previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) NSCLC.
2. If male, must agree to use contraception or practice abstinence as well as refrain from donating sperm during the treatment period and for the time needed to eliminate each study intervention after the last dose of study intervention.
3. If female, may participate if not pregnant or breastfeeding, and at least one of the following conditions apply: 1) not a woman of childbearing potential (WOCBP); or 2) a WOCBP who agrees to follow contraceptive guidance during the treatment period and for the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
4. 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 programmed death-ligand 1 (PD-L1) testing.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days of randomization.
6. Have adequate organ function.

Exclusion criteria 19

1. Has one of the following tumor locations/types:1) NSCLC involving the superior sulcus; 2) Large cell neuro-endocrine cancer (LCNEC); or 3) Sarcomatoid tumor.
2. Has a history of (non-infectious) pneumonitis /interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease that requires steroids.
3. Has an active infection requiring systemic therapy.
4. Has had an allogenic tissue/sold organ transplant.
5. Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients.
6. Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents and/or to any of their excipients.
7. Has an active autoimmune disease that has required systemic treatment in past 2 years.
8. Has a known history of human immunodeficiency virus (HIV) infection.
9. Has a known history of Hepatitis B or Hepatitis C.
10. Has a known history of active tuberculosis.
11. 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.
12. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
13. 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.
14. Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy prior to randomization/allocation.
15. Has received prior radiotherapy within 2 weeks of start of trial treatment.
16. Has received a live vaccine within 30 days prior to the first dose of trial drug.
17. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
18. Has a diagnosis of immunodeficiency or is receiving either systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.
19. Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Event Free Survival (EFS)
2. Overall Survival (OS)

Secondary endpoints 6

1. Major Pathological Response (mPR) Rate
2. Pathological Complete Response (pCR) Rate
3. Global Health Status/Quality of Life (GHS/QoL) Score using the European Organization for Research and Treatment (EORTC) QoL Questionnaire (QLQ-C30)
4. Adverse Events (AEs)
5. Perioperative Complications
6. Treatment Discontinuations Due to AEs

Investigational products

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

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Steven Keller

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Steven Keller

Third parties 9

Locations

11 EU/EEA countries · 60 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

Documents 65 files

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

Application history

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