Trial Exploring Combined Neoadjuvant Therapy With Pembrolizumab/Lenvatinib + Adjuvant Pembrolizumab in Pat. With NSCLC

NCT04875585 | Recruiting Phase 2

• 1 other identifier: INNWOP2020
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of this single arm, phase II study is to determine the efficacy of the combination therapy Pembrolizumab/Lenvatinib regarding the rate of major pathological response (MPR-Rate). The investigators expect to improve the MPR-Rate of 20% in Anti-PD1/-PD-L1 monotherapy (observed in recent trials) to a MPR-Rate of 40% with the combination therapy Pembrolizumab/Lenvatinib.

Conditions

Non Small Cell Lung Cancer

Keywords

NSCLC

Outcome Measures

Primary Outcomes (1)

• Major pathological response after neoadjuvant immunotherapy in combination with angiogenesis inhibition

  Number of Participants Reaching a Major Pathological Response after Short Course Neoadjuvant Treatment with Pembrolizumab/Lenvatinib.

  2 years

Secondary Outcomes (5)

• Radiologic response according to RECIST/iRECIST

  2 years

• Surgical resection rate

  2 years

• Disease free survival at 1, 2, 3 and 5 years

  5 years

• Overall survival at 1, 2, 3 and 5 years

  5 years

• Capturing of the Toxicity of a neoadjuvant/adjuvant treatment

  5 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

neoadjuvant therapy with Pembrolizumab/Lenvatinib in combination with surgical resection of primary tumor followed by adjuvant Pembrolizumab therapy

Drug: neoadjuvant therapy with Pembrolizumab/Lenvatinib; Procedure: Surgery; Drug: Adjuvant Treatment Phase

Interventions

neoadjuvant therapy with Pembrolizumab/Lenvatinib DRUG

Neoadjuvant therapy for 6 weeks

Treatment Arm

Surgery PROCEDURE

surgical resection of primary tumor and lymph-node-dissection.

Treatment Arm

Adjuvant Treatment Phase DRUG

Adjuvant treatment with 15 cycles of Pembrolizumab

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants ≥18 years of age
• Histologically confirmed primary diagnosis of resectable NSCLC, stages IA3-IIIA (max. single station N2).
• Measurable disease based on RECIST 1.1.
• 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.
• Female participants are eligible to participate if not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• 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.
• Written informed consent provided
• ECOG performance status of 0 to 1
• Adequate organ function. Specimens must be collected within 14 days prior to the start of study treatment.

You may not qualify if:

• Uncontrolled blood pressure (systolic BP\>160mmHg or diastolic BP \>95mmHg) despite an optimized regimen of antihypertensive medication.
• 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.
• History of prolonged QT syndrome, or family member with prolonged QT syndrome
• QTc interval \>490 msec when 3 consecutive ECG values are averaged
• Bleeding and/or thrombotic disorders and/or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following Lenvatinib therapy.
• 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.
• 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).
• Patient has received prior systemic anti-cancer therapy for the newly diagnosed NSCLC including investigational agents.
• Patient has received prior radiotherapy for the newly diagnosed NSCLC.
• Patient 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.
• 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.
• 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.
• Known additional malignancy that is progressing.
• Known history of severe (≥Grade 3) allergic or hypersensitivity reactions to Pembrolizumab or Lenvatinib and/or any of their excipients.

Sponsors & Collaborators

• Medical University Innsbruck: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Medical University Innsbruck

Innsbruck, Tyrol, 6020, Austria

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Neoadjuvant Therapy; pembrolizumab; lenvatinib; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Georg Pall, Dr.

  Georg.Pall@i-med.ac.at

  PRINCIPAL INVESTIGATOR

Central Study Contacts

KKS Innsbruck

CONTACT

+43 0512 09003; kks-regulatory@i-med.ac.at

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: May 6, 2021
• Study Start: May 12, 2021
• Primary Completion: December 1, 2023
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 24, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)