Lenvatinib and Pembrolizumab for Well-Differentiated G3 Neuroendocrine Tumors
This study is looking at a combination of two drugs, Lenvatinib and Pembrolizumab, for people with a specific type of cancer called well-differentiated grade 3 neuroendocrine tumors (WD G3 NET). These tumors can start in the pancreas, stomach, intestines, lungs, or other areas. Researchers want to see how many people respond to this treatment. You would receive Lenvatinib by mouth and Pembrolizumab through an IV. The study also involves special imaging and blood and tumor samples to understand how the treatment affects the tumor. This is a new area of study, as WD G3 NETs were only recently recognized as a distinct type of tumor. The study aims to enroll 29 participants.
- Study design
- This is a single-arm study, meaning all participants receive the same treatment. It is a Phase II study, which typically evaluates the effectiveness and safety of a new treatment in a larger group of people.
- What's involved
- The study involves receiving Lenvatinib orally and Pembrolizumab intravenously. It also includes serial blood samples, tumor biopsies, and special imaging.
- Compensation
- Not stated in the trial record.
- Follow-up
- The main goal of the study, overall response rate, will be measured for up to 24 months.
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NCT05746208
Lenvatinib Plus Pembrolizumab in Well Differentiated G3 Neuroendocrine Tumors
Recruiting
PHASE2Ages 18+InterventionalTreatmentUniversity of California, San FranciscoInvestigator-initiated
~29 participants
Updated 2026-03-17 on ClinicalTrials.gov
What's tested:LenvatinibPembrolizumabHyperpolarized 13C-Pyruvate
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall Response Rate (ORR)
Measured over Up to 24 months
Conditions
Where it's being run
1 sites across 1 statesCalifornia1
Study leadership
- Emily Bergsland, MD · PRINCIPAL_INVESTIGATOR · University of California, San Francisco
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
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%. 3. 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). 4. 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. 2. At least 1 measurable target lesion according to RECIST 1.1, including the following criteria.
Adequate bone marrow function:
Absolute neutrophil count \>=1,500/microliter (mcL)
Platelets \>=100,000/mcL
Hemoglobin \>=1,500/mcL
Hemoglobin \>=9.0 g/dL or \>=5.6 mmol/L.
Adequate hepatic function,
Total bilirubin \<=1.5 X institutional upper limit of normal, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT) \<=2.5 X institutional upper limit of normal (ULN) (\<=5 × ULN for participants with liver metastases).
Adequate renal function,
Creatinine \<= 1.5 x institutional upper limit of normal OR
Creatinine clearance \>=30 mL/min for participant with creatinine levels \>1.5 × institutional ULN,
Urine protein-to-creatinine ratio (UPCR) \<1 (unless urine protein \<1 g/24 hour) OR
Urine protein dipstick \<= 1+(unless urine protein \<1 g/24 hour).
Coagulation: International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) \<=1.5 × ULN unless participant is receiving anticoagulant therapy (and PT or aPTT is within therapeutic range of intended use of anticoagulants). 8. Participant (or legally acceptable representative) must have the ability to understand a written informed consent document, and the willingness to sign it. 9. Adequately controlled blood pressure (BP) with or without anti-hypertensive medications, defined as BP \<140/90 (NOTE: BP should be controlled without a change in medications within one week of day 1 cycle 1). 10. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. 11. Must have a life expectancy of greater than 3 months, as determined by the investigator. 12. Stage 2 patients must agree to have a biopsy of the primary tumor or metastatic tissue at baseline, and there must be a lesion that can be biopsied with acceptable clinical risk (as judged by the investigator).
Formalin-fixed, paraffin-embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. 13. Male participants are eligible to participate if they agree to the following starting with the first dose of study therapy through 7 days after the last dose of lenvatinib (and refrain from donating sperm during this period).
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR Must agree to use contraception (see appendix 5) unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
Please note that 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed. 14. Female participants are eligible if not pregnant or breastfeeding, and at least 1 of the following conditions applies during the intervention period and for at least 120 days post pembrolizumab or 30 days post lenvatinib, whichever occurs last:
Not be a woman of childbearing potential (WOCBP), e.g., postmenopausal (no menses for \> 1 year) or permanently sterilized.
Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency.
Abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) NOTE: The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention.
Exclusion
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. 7. 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. 8. Hypersensitivity (\>=G3) or known intolerance to lenvatinib or pembrolizumab or any of its excipients. 9. Serious non-healing wound, ulcer, or bone fracture. 10. Bleeding or thrombotic disorders or participants at risk for severe hemorrhage. 11. 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. 12. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL before the first dose of study drug. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study treatment.
Participants who are positive for anti-Hepatitis B Core (HBc), negative for HbsAg, and negative or positive for anti-HBs, and who have an HBV viral load under 100 IU/mL, do not require HBV antiviral prophylaxis 18. Is known to have active tuberculosis (TB, Bacillus tuberculosis). 19. Diagnostic assessments:
A woman of child bearing potential (WOCBP) must have a negative highly sensitive pregnancy test (urine or serum) within 14 days of the first dose of the study intervention.
If a urine test cannot be confirmed as negative (e.g., a positive or an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Similarly, a WOCBP must have a negative urine pregnancy test if the serum pregnancy test is positive (and thought to be spurious/from underlying malignancy). 21. Women who are breastfeeding are excluded from the study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenvatinib plus pembrolizumab (breastfeeding should be discontinued if the mother is treated with lenvatinib plus pembrolizumab). 22. Has a history or current evidence of any condition, therapy, or laboratory abnormality (including electrolyte abnormalities that have not been corrected, e.g., potassium, calcium, magnesium) that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 23. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.
What this trial measures
- Overall Response Rate (ORR)Up to 24 months
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.