Lenvatinib Plus Pembrolizumab in Well Differentiated G3 Neuroendocrine Tumors

NCT05746208 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 22958NCI-2023-01199
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This is the first study to be done in a newly described class of neuroendocrine tumors known as well-differentiated grade 3 neuroendocrine tumors (WD G3 NET). First described in the pancreas in 2017, the classification was broadened to include gastrointestinal tract tumors in 2019. Recent data suggest an equivalent subtype exists in the lungs (NEC with carcinoid morphology). WD G3 NETs can occur de novo as well as the result of grade progression over time. This is a single arm, multi-site, Phase II study in biomarker "unselected" participants. This study will also incorporate serial blood samples, tumor biopsies, and special imaging to better understand the impact of therapy on the tumor and microenvironment. Hyperpolarized (HP) 13C-pyruvate magnetic resonance imaging (MRI) - a novel non-radioactive imaging modality able to provide in vivo measurements of the pyruvate-to-lactate conversion rate (kpl).

Conditions

Neuroendocrine Tumors; Well-Differentiated Neuroendocrine Carcinoma; High Grade Neuroendocrine Carcinoma, Any Site

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as a complete response (CR) or a partial response (PR) according to RECIST version 1.1 criteria. The All Subjects as Treated (ASaT, ITT) population will be used for analysis which consists of all participants who received at least one dose of the study treatment. Participants without at least confirmatory scan will be classified as non-responders. The point estimate and 95% confidence interval will be reported.

  Up to 24 months

Secondary Outcomes (4)

• Proportion of participants with maximum grade, treatment-related Adverse Events

  Up to 27 months

• Median duration of response

  Up to 24 months

• Median Progression-Free Survival at 18 weeks

  Up to 18 weeks

• Median Progression-Free Survival

  Up to 27 months

Study Arms (1)

Lenvatinib Plus Pembrolizumab

EXPERIMENTAL

Participants will receive 20 mg once daily of lenvatinib plus 400 mg of pembrolizumab every 6 weeks for up to 18 doses. Eligible participants may also receive a Hyperpolarized 13C-pyruvate (HP 13C) magnetic resonance imaging (MRI) scan

Drug: Lenvatinib; Drug: Pembrolizumab; Drug: Hyperpolarized 13C-Pyruvate

Interventions

Lenvatinib DRUG

Given orally

Also known as: Lenvima

Lenvatinib Plus Pembrolizumab

Pembrolizumab DRUG

Given IV

Also known as: Keytruda

Lenvatinib Plus Pembrolizumab

Hyperpolarized 13C-Pyruvate DRUG

Given IV

Also known as: HP 13C

Lenvatinib Plus Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Participants must have locally advanced or unresectable histologically or cytologically confirmed WD G3 NET.
• pancreas primary.
• other primary sites:
• gastrointestinal site,
• unknown primary site,
• lung neuroendocrine carcinoma with carcinoid morphology, or
• other non-pancreatic primary sites with well-differentiated (WD) morphology and Ki67 \> 20%.
• WD G3 NET occurring de novo or in the setting of grade progression allowed (provided WD G3 NET is thought to be the dominant histology at the time of enrollment).
• Tumors with ambiguous histology and/or Ki67 \>/=55% must be reviewed at the participating site to confirm that they are not poorly differentiated. Tumors with confirmed ambiguous histology will be considered eligible.
• At least 1 measurable target lesion according to RECIST 1.1, including the following criteria.
• non-nodal lesion that measures \>=1.0 cm in the longest diameter.
• lymph node (LN) lesion that measures as \>=1.5 cm in the short axis.
• the lesion is suitable for repeat measurement using computed tomography (CT) / magnetic resonance imaging (MRI) (CT/MRI).
• lesions previously treated with radiation or other locoregional therapy are considered measurable if progression has been demonstrated in such lesions.
• in the setting of grade progression, every attempt should be made to select measurable target lesions that are thought to represent G3 disease (based on biopsy results, tumor growth rate, or other features).

You may not qualify if:

• Has poorly differentiated neuroendocrine carcinoma (e.g., small cell NEC, large cell NEC, Merkel cell carcinoma, prostate neuroendocrine carcinoma) or WD Grades 1 or 2 NET (without evidence of G3 NET).
• Uncontrolled blood pressure (BP) (Systolic BP \>=140 mmHg or diastolic BP \>=90 mmHg) despite an optimized regimen of antihypertensive medication.
• Significant gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.
• Has pre-existing \>= grade 3 (G3) gastrointestinal or non-gastrointestinal fistula.
• Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention, including New York Heart Association (NYHA) Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted
• Radiographic evidence of major blood vessel invasion/infiltration (e.g., carotid artery) or intratumoral cavitation in the chest (e.g. tumors above the diaphragm).
• 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. NOTE: Vascular encasement may be allowed in selected cases below the diaphragm; clinical judgement must be employed. Eligible tumors may include:
• Portal vein or inferior vena cava involvement by tumor is allowed at the discretion of the investigator (and is distinguished from invasion through the wall of a vessel.
• Vascular encasement by tumor below diaphragm is allowed at the discretion of the investigator, Examples of potentially eligible tumors include: mesenteric mass encasing superior mesenteric artery (SMA)/superior mesenteric vein (SMV), splenic vein involvement from a pancreas primary tumor, or lymphadenopathy adjacent to the inferior vena cava, portal vein, or other vessels without a clear plane between the tumor and vessel).
• Vascular encasement by the tumor in the abdomen, such as a mesenteric mass encasing the SMV/SMA, must be distinguished from invasion through the wall of a vessel and with consideration of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
• Active hemoptysis or tumor bleeding (bright red blood of at least 0.5 teaspoons) within 3 weeks prior to the first dose of study drug.
• Hypersensitivity (\>=G3) or known intolerance to lenvatinib or pembrolizumab or any of its excipients.
• Serious non-healing wound, ulcer, or bone fracture.
• Bleeding or thrombotic disorders or participants at risk for severe hemorrhage.
• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

lenvatinib; pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Emily Bergsland, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Luan

CONTACT

(415) 514-6220; Jennifer.Luan@ucsf.edu

Study Design

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

Study Record Dates

• First Submitted: February 17, 2023
• First Posted: February 27, 2023
• Study Start: July 17, 2023
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)