Phase II trial exploring combined neoadjuvant therapy with Pembrolizumab/Lenvatinib and adjuvant Pembrolizumab in patients with surgically resectable Non-Small- Cell Lung Cancer (NSCLC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medizinische Universitaet Innsbruck

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

12 May 2021 → ongoing

Decision date (initial)

2024-09-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514821-45-00

EudraCT number

2020-004707-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The rate of major pathological response (MPR) upon neoadjuvant combination therapy with Pembrolizumab and Lenvatinib.

Secondary objectives 2

1. Identification of response-predicting biomarkers for combined Pembrolizumab plus Lenvatinib treatment using multi-omics.
2. Monitoring of disease-kinetics and potential efficacy-predicting biomarkers during adjuvant Pembrolizumab treatment using liquid-biopsy-techniques.

Conditions and MedDRA coding

Non-Small-Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male/female participants ≥18 years of age
2. Histologically or cytologically confirmed primary diagnosis of resectable NSCLC, stages IA2 (minimum primary-tumor diameter 1,5cm) - IIIA (max. single station N2).
3. Measurable disease based on RECIST 1.1.
4. Male participants must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 additional days after the last dose of study treatment and refrain from donating sperm during this period.
5. Female participants are eligible to participate if not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
6. Written informed consent provided
7. ECOG performance status of 0 to 1
8. Adequate organ function. Specimens must be collected within 14 days prior to the start of study treatment.

Exclusion criteria 23

1. A woman with child-bearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to inclusion (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. Uncontrolled blood pressure (systolic BP>160mmHg or diastolic BP >95mmHg) despite an optimized regimen of antihypertensive medication.
3. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, and/or cardiac arrhythmia requiring medical treatment at screening.
4. History of prolonged QT syndrome, or family member with prolonged QT syndrome
5. QTc interval >490 msec when 3 consecutive ECG values are averaged
6. Radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered cause for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy. (In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta).
7. Subjects having > 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is <1 g/24 hours.
8. Patient 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 (eg, CTLA-4, OX 40, CD137).
9. Patient has received prior systemic anti-cancer therapy for the newly diagnosed NSCLC including investigational agents.
10. Patient has received prior radiotherapy for the newly diagnosed NSCLC.
11. Patient has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
12. Patient 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 treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
13. Diagnosis of immunodeficiency and/or patient 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 to the first dose of study drug.
14. Known additional malignancy that is progressing.
15. Known history of severe (≥Grade 3) allergic or hypersensitivity reactions to Pembrolizumab or Lenvatinib and/or any of their excipients.
16. Known active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
17. History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
18. Active infection requiring systemic therapy.
19. Infection with Human Immunodeficiency Virus (HIV).
20. Infection with Hepatitis B and/or Hepatitis C
21. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
22. Patient has received prior surgery therapy for the newly diagnosed NSCLC.
23. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening visit through 120 days after the last dose of trial treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Achievment of major pathological response after neoadjuvant immunotherapy in combination with angiogenesis inhibition

Secondary endpoints 5

1. Radiologic response according to RECIST/iRECIST
2. Surgical resection rate
3. Disease free survival at 1, 2, 3 and 5 years
4. Overall survival at 1, 2, 3 and 5 years
5. Feasibility and safety of a neoadjuvant/adjuvant treatment

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medizinische Universitaet Innsbruck

Sponsor organisation

Medizinische Universitaet Innsbruck

Address

Innrain 52

City

Innsbruck

Postcode

6020

Country

Austria

Scientific contact point

Organisation

Medizinische Universitaet Innsbruck

Contact name

University Hospital for Internal Medicine V

Public contact point

Organisation

Medizinische Universitaet Innsbruck

Contact name

University Hospital for Internal Medicine V

Locations

1 EU/EEA country · 1 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 5 files

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

Application history

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