A Study of Etoposide-carboplatin in Combination With Pembrolizumab and Lenvatinib Maintenance in HG-NETs

NCT06232564 | Active Not Recruiting Phase 2

• 1 other identifier: 1004397
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single arm, phase II multicentre study designed to evaluate the efficacy and safety of pembrolizumab in combination with carboplatin and etoposide chemotherapy followed by pembrolizumab and lenvatinib maintenance therapy in patients with HG-NETs who are chemotherapy-naïve for their metastatic disease. The study will be conducted in up to 10 sites and will recruit up to a maximum of 20 evaluable participants.

Conditions

Neuroendocrine Tumors

Keywords

HG-NETs

Outcome Measures

Primary Outcomes (1)

• Evaluation of the effects of carboplatin, etoposide and pembrolizumab followed by pembrolizumab and lenvantinib maintenance in treatment naïve HG-NETs as measured by RECIST v1.1 criteria.

  To evaluate overall response rates (ORR) as measured by RECIST v1.1 criteria.

  2 Years

Secondary Outcomes (1)

• Investigation of adverse events from treatment of carboplatin, etoposide and pembrolizumab followed by pembrolizumab and lenvatinib maintenence.

  2 Years

Other Outcomes (3)

• To Assess tumour infiltrating lymphocyte profiling

  2 Years

• Immunohistochemistry

  2 Years

• Blood testing for characterisation of cells

  2 Years

Study Arms (1)

Open Label, Single Arm, Phase II Study

EXPERIMENTAL

This is an open label, single arm, phase II multicentre study designed to evaluate the efficacy and safety of pembrolizumab in combination with carboplatin and etoposide chemotherapy followed by pembrolizumab and lenvatinib maintenance therapy in patients with HG-NETs who are chemotherapy-naïve for their metastatic disease. The study will be conducted in up to 10 sites and will recruit up to a maximum of 20 evaluable participants.

Combination Product: Pembrolizumab in combination with carboplatin and etoposide chemotherapy followed by pembrolizumab and lenvatinib maintenance therapy

Interventions

Pembrolizumab in combination with carboplatin and etoposide chemotherapy followed by pembrolizumab and lenvatinib maintenance therapy COMBINATION_PRODUCT

Pembrolizumab in combination with carboplatin and etoposide chemotherapy followed by pembrolizumab and lenvatinib maintenance therapy

Open Label, Single Arm, Phase II Study

Eligibility Criteria

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

You may qualify if:

• In order to be eligible for participation in this trial, the participant must:
• Be willing and able to provide written informed consent for the trial.
• Be 18 years or above of age on day of signing informed consent.
• ECOG performance status of 0-2.
• Have histologically or cytologically confirmed diagnosis of poorly differentiated neuroendocrine carcinoma.
• Have Ki-67 labelling index \>20% and/or \>20 mitoses/10 high-power fields.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have had no prior systemic treatment in the metastatic setting.
• Demonstrate adequate organ function.
• Female subject of childbearing potential should have a negative urine or serum pregnancy. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Women of childbearing potential must be willing to use a highly effective method of contraception for the course of the study through 120 days after the last dose of Investigational Medicinal Product (IMP).
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Sexually active males must agree to use an adequate method of contraception starting with the first dose of IMP through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• The participant must be excluded from participating in the trial if the participant:
• Has a diagnosis of large cell and small cell histology of lung origin or Merkel cell carcinoma.
• 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 to the first dose of study drug.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease and stereotactic radiotherapy to the CNS.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA detectable levels) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• Has a known history of active Bacillus Tuberculosis (TB).
• Has a known history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has a known history of interstitial of lung disease.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has 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.
• Uncontrolled blood pressure (Systolic BP\>140 mmHg or diastolic BP \>90 mmHg) in spite of 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.
• Bleeding or thrombotic disorders or subjects at risk for severe haemorrhage. The degree of tumour invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe haemorrhage associated with tumour shrinkage/necrosis following lenvatinib therapy.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

Related Publications (1)

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

pembrolizumab; Carboplatin

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open Label, Single Arm

Study Record Dates

• First Submitted: December 14, 2023
• First Posted: January 30, 2024
• Study Start: July 8, 2024
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): October 15, 2027
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)