Phase II Study of Pembrolizumab and Lenvatinib in Advanced Well-differentiated Neuroendocrine Tumors

NCT03290079 | Completed Phase 2 Results FDA Drug

• 1 other identifier: MCC-19207
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to:

• Assess overall radiographic response rate (ORR)
• Assess progression-free survival (PFS)
• Test the safety and tolerability of Pembrolizumab in combination with lenvatinib

Conditions

Neuroendocrine Tumors; Neuroendocrine Carcinoma; Neuroendocrine Cancer

Keywords

well-differentiated neuroendocrine tumors

Outcome Measures

Primary Outcomes (1)

• Objective Radiographic Response Rate (ORR)

  Response Evaluation Criteria in Solid Tumors (RECIST) based response rate. Complete Response (CR): Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 mm in short axis. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest). The SLD must also demonstrate an absolute increase of at least 5mm. (Two lesions increasing from 2 mm to 3 mm, for example, does not qualify). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  Up to 12 months

Secondary Outcomes (3)

• Duration of Response (DOR)

  Up to 12 months

• Progression Free Survival (PFS)

  Up to 12 months

• Overall Survival (OS)

  At 12 months

Study Arms (1)

Pembrolizumab & Lenvatinib treatment

EXPERIMENTAL

Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks, in addition to 20 mg Lenvatinib by mouth every day of each 3 week cycle. Estimated average length of treatment per participant: 4 months.

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

200 mg Pembrolizumab by IV on Day 1 of each 3 week cycle.

Also known as: Keytruda®

Pembrolizumab & Lenvatinib treatment

Lenvatinib DRUG

20 mg Lenvatinib by mouth every day of each 3 week cycle

Also known as: Lenvima®

Pembrolizumab & Lenvatinib treatment

Eligibility Criteria

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

You may qualify if:

• Diagnosis/Condition for entry into the trial: Metastatic well differentiated neuroendocrine tumors of primary lung, thymic, small bowel and colorectal origin (including unknown primary)
• Evidence of radiographic disease progression with scan documenting progression occurring within 8 months of signing informed consent
• At least two prior lines of systemic treatment. If the only prior line of treatment was adjuvant or neoadjuvant, patient must have completed treatment within 12 months. There is no limit to number of prior therapies.
• Willing and able to provide written informed consent/assent for the trial.
• ≥ 18 years of age on day of signing informed consent.
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function and laboratory values. All screening labs should be performed within 14 days of treatment initiation.
• Females of childbearing potential (FOCBP) should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication.
• FOCBP must agree to use adequate contraception as outlined in study documentation for the course of the through 120 days after the last dose of study medication.
• Male participants of childbearing potential must agree to use an adequate method of contraception as outlined in study documentation, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Poorly differentiated neuroendocrine carcinoma
• Pancreatic neuroendocrine tumor
• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Potential participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If have received major surgery within 3 weeks, must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
• Serious non-healing wound, ulcer or bone fracture
• Has pre-existing \>/= Grade 3 gastrointestinal (GI) or non-GI fistula
• Has significant cardiovascular impairment within 12 months of the first dose of study drug
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Potential participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
• History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Neuroendocrine Tumors; Carcinoma, Neuroendocrine

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Results Point of Contact

• Title: Jonathan Strosberg, MD
• Organization: Moffitt Cancer Center

jonathan.strosberg@moffitt.org

813-745-5553

Study Officials

• Jonathan Strosberg, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Simon 2-stage design

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: September 21, 2017
• Study Start: December 15, 2017
• Primary Completion: January 10, 2023
• Study Completion: May 13, 2024
• Last Updated: December 22, 2025
• Results First Posted: March 26, 2024

Record last verified: 2025-12

Locations

US (1)