Lenvatinib and Pembrolizumab in People With Advanced Adenoid Cystic Carcinoma and Other Salivary Gland Cancers

NCT04209660 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 19-310
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to see if the study drugs, lenvatinib and pembrolizumab, are effective in treating advanced Adenoid Cystic Carcinoma (ACC) or other salivary gland cancers that have come back and/or spread to other parts of the body. Researchers are also doing this study to test the safety of the study drugs in participants.

Conditions

Adenoid Cystic Carcinoma; Salivary Gland Cancer

Keywords

Lenvatinib; Pembrolizumab; 19-310

Outcome Measures

Primary Outcomes (1)

• best overall response rate

  Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

  2 years

Secondary Outcomes (1)

• median progression-free survival (PFS)

  2 years

Study Arms (2)

recurrent/metastatic adenoid cystic carcinoma (R/M ACC)

EXPERIMENTAL

All eligible patients will undergo informed consent and screening for trial enrollment. Enrolled patients will receive a starting lenvatinib dose of 20mg daily taken orally and pembrolizumab 200mg intravenously every 3 weeks (1 cycle=3 weeks)

Drug: Lenvatinib; Drug: Pembrolizumab

recurrent/metastatic non-ACC salivary gland cancers (R/M SGC).

EXPERIMENTAL

All eligible patients will undergo informed consent and screening for trial enrollment. Enrolled patients will receive a starting lenvatinib dose of 20mg daily taken orally and pembrolizumab 200mg intravenously every 3 weeks (1 cycle=3 weeks)

Drug: Lenvatinib; Drug: Pembrolizumab

Interventions

Lenvatinib DRUG

Lenvatinib 20mg daily (two 10mg lenvatinib capsules) taken orally will be administered with water orally once a day (with or without food) in 21-day cycles at approximately the same time each day.

recurrent/metastatic adenoid cystic carcinoma (R/M ACC); recurrent/metastatic non-ACC salivary gland cancers (R/M SGC).

Pembrolizumab DRUG

Pembrolizumab (200mg) will be administered as a 30-minute IV infusion, Q3W +/-3 days (infusions lasting between 25-40 minutes are acceptable on C1D1.

recurrent/metastatic adenoid cystic carcinoma (R/M ACC); recurrent/metastatic non-ACC salivary gland cancers (R/M SGC).

Eligibility Criteria

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

You may qualify if:

• ACC Cohort (Cohort 1) only: Patients must have pathologically or cytologically confirmed adenoid cystic carcinoma. Cancers arising from non-salivary gland primary sites are allowed.
• Non-ACC Cohort (Cohort 2) only: Patients must have pathologically or cytologically confirmed salivary gland cancer of any histology (except for adenoid cystic carcinoma that is enrolled into cohort 1).
• Patients must have recurrent and/or metastatic disease not amenable to other curative intent therapy.
• At least 4 weeks must have elapsed since the end of prior systemic treatment and/or since completion of radiotherapy with resolution of all treatment related toxicity to NCI CTCAE Version 5.0 grade ≤1 (or tolerable grade 2) or back to baseline (except for alopecia, lymphopenia, or hypothyroidism) prior to starting study drug treatment.
• Patients must have RECIST V1.1 measurable disease defined as at least one non-nodal lesion measuring ≥ 20 mm with conventional techniques or as ≥10mm with CT scan, MRI, or calipers by clinical exam in the longest dimension AND/OR a nodal lesion measuring \> 15 mm in the shortest dimension. Tumors in previously irradiated fields may be considered measurable if there is evidence of tumor progression after radiation treatment.
• Cohort 1 and acinic cell carcinoma patients in Cohort 2 only: Patients must have documentation of a new or progressive lesion on radiologic imaging study performed within 6 months prior to study enrollment (progression of disease over any interval is allowed) and/or new/worsening disease related symptoms within 6 months prior to study enrollment. Note: This assessment will be performed by the treating investigator and evidence of progression by RECIST criteria is not required.
• Age ≥ 18 years of age on the day of signing informed consent.
• ECOG performance status 0 or 1 (or Karnofsky ≥ 70%).
• Patients must have tissue from the primary tumor or metastases available for correlative studies. Either a paraffin block or at least 20 unstained slides are acceptable (paraffin block or at 30 unstained slides would be ideal). Patients without available tissue for submission may still be eligible if approved by the Principal Investigator.
• Screening laboratory values must meet the following criteria:
• Neutrophils ≥1500/μL
• Platelets ≥ 100x10\^3/μL
• Hemoglobin ≥ 9.0 g/dL (without packed red blood cell (pRBC) transfusion within the last 2 weeks)
• AST and ALT ≤ 2.5 x ULN (if liver metastases are present, AST and ALT ≤ 5x ULN)
• Total Bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 x ULN (except participants with Gilbert Syndrome, who can have a total bilirubin \< 3.0 mg/dL)

You may not qualify if:

• Untreated metastatic brain (subjects with treated brain metastases will be eligible, provided that they are radiographically 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 the first dose of study treatment).
• Concurrent anti-cancer therapy (chemotherapy, definitive radiation therapy, surgery, immunotherapy, biologic therapy or tumor embolization) other than study treatment. Concurrent therapy with bisphosphonates or denosumab for bone metastases is allowed, provided they are started prior to study entry. Palliative radiation to non-target lesions is also allowed.
• Prior malignancy if diagnosed and treated within 2 years of trial drug initiation (with the exception of non-melanomatous skin cancers). Patients may be included if they have completed therapy for a prior malignancy \>2 years prior to drug initiation and are currently NED. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (breast DCIS, or cervical CIS) that have undergone potentially curative at any time therapy are not excluded from trial participation.
• History of allergy or intolerance to study drug components (or any of their excipients), or severe (\> Grade 3) hypersensitivity reaction to any excipients of pembrolizumab or any monoclonal antibody.
• Prior use of lenvatinib or any PD-1/PD-L1 or anti-PD-L2 targeted therapies or with an agent directed at another stimulatory or co-inhibitory T-cell receptor (CTLA-4, OX-40, CD137).
• Uncontrolled hypertension (systolic pressure \>140mm Hg or diastolic pressure \>90mm Hg), despite optimal medical management.
• Prior systemic anti-cancer therapy including use of another investigational drug or device (i.e., outside study treatment) during, or within 4 weeks of trial entry (time of initiation of experimental drug).
• Clinically significant proteinuria:
• °Subjects having \>1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with proteinuria ≥1gm/24-hour will be ineligible.
• Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
• New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months (baseline echocardiogram is not required unless clinically indicated).
• Subjects with thrombotic, embolic, venous or arterial events, such as cerebrovascular accidents (including transient ischemic attacks), deep venous thrombosis or pulmonary embolism within 6 months of study treatment start.
• Prolongation of QTc interval to \>480 msec
• Any hemorrhage or bleeding event ≥ NCI CTCAE v5.0 Grade ≥3 within 4 weeks prior to start of study medication.
• Active infection (any infection requiring systemic treatment)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• Eisai Inc.: collaborator

Study Sites (8)

Baptist Alliance MCI

Miami, Florida, 33143, United States

Location

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (All protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (All Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Tchekmedyian V. Salivary Gland Cancers. Hematol Oncol Clin North Am. 2021 Oct;35(5):973-990. doi: 10.1016/j.hoc.2021.05.011.

  PMID: 34503735 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic; Salivary Gland Neoplasms

Interventions

lenvatinib; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases

Study Officials

• Alan Ho, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase II study evaluating the efficacy of lenvatinib plus pembrolizumab in the treatment of progressive, recurrent/metastatic adenoid cystic carcinoma (R/M ACC) and recurrent/metastatic non-ACC salivary gland cancers (R/M SGC). Patients will be enrolled in two cohorts: Cohort 1, patients with R/M ACC ("ACC group"), and Cohort 2: patients with R/M SGC ("non-ACC group").

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: December 24, 2019
• Study Start: June 2, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (8)