Lenvatinib and Pembrolizumab in People With Advanced Soft Tissue Sarcoma

NCT04784247 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 21-047
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to find out whether combining the study drugs, lenvatinib and pembrolizumab, is a safe and effective treatment for metastatic soft tissue sarcomas that cannot be removed with surgery.

Conditions

Advanced Sarcoma

Keywords

Lenvatinib; Pembrolizumab; Metastatic and/or unresectable soft tissue sarcomas; 21-047

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)

  at 27 weeks

Secondary Outcomes (1)

• progression-free survival (PFS)

  27 weeks

Study Arms (5)

Leiomyosarcoma

EXPERIMENTAL

Patients enrolled in the study will be treated initially with a 2 week run-in of lenvatinib 20 mg orally daily. Subsequently, they will start pembrolizumab 200 mg intravenously every 3 weeks (21-day cycles). Treatment will continue until progression or other indications for study withdrawal Otherwise, treatment will be discontinued after a maximum of 35 cycles of pembrolizumab (approximately 2 years) or after achieving CR. RECIST v1.1 tumor assessments will be made at baseline (CT or MRI) and approximately every 3 cycles (or every 9 weeks +/- 1 week) for the first 9 cycles (27 weeks), then every 4 cycles (or every 12 weeks +/- 1week). Patients who progress after having discontinued therapy after completing 2 years of treatment or after achieving confirmed CR may be eligible to reinitiate therapy for an additional 1 year (approximately 17 cycles).

Drug: Lenvatinib; Drug: Pembrolizumab

High grade undifferentiated pleomorphic sarcoma

EXPERIMENTAL

Patients enrolled in the study will be treated initially with a 2 week run-in of lenvatinib 20 mg orally daily. Subsequently, they will start pembrolizumab 200 mg intravenously every 3 weeks (21-day cycles). Treatment will continue until progression or other indications for study withdrawal . Otherwise, treatment will be discontinued after a maximum of 35 cycles of pembrolizumab (approximately 2 years) or after achieving CR. RECIST v1.1 tumor assessments will be made at baseline (CT or MRI) and approximately every 3 cycles (or every 9 weeks +/- 1 week) for the first 9 cycles (27 weeks), then every 4 cycles (or every 12 weeks +/- 1week). Patients who progress after having discontinued therapy after completing 2 years of treatment or after achieving confirmed CR may be eligible to reinitiate therapy for an additional 1 year (approximately 17 cycles).

Drug: Lenvatinib; Drug: Pembrolizumab

Vascular sarcomas (including angiosarcoma and epithelioid hemangioendothelioma)

EXPERIMENTAL

Patients enrolled in the study will be treated initially with a 2 week run-in of lenvatinib 20 mg orally daily. Subsequently, they will start pembrolizumab 200 mg intravenously every 3 weeks (21-day cycles). Treatment will continue until progression or other indications for study withdrawal. Otherwise, treatment will be discontinued after a maximum of 35 cycles of pembrolizumab (approximately 2 years) or after achieving CR. RECIST v1.1 tumor assessments will be made at baseline (CT or MRI) and approximately every 3 cycles (or every 9 weeks +/- 1 week) for the first 9 cycles (27 weeks), then every 4 cycles (or every 12 weeks +/- 1week). Patients who progress after having discontinued therapy after completing 2 years of treatment or after achieving confirmed CR may be eligible to reinitiate therapy for an additional 1 year (approximately 17 cycles).

Drug: Lenvatinib; Drug: Pembrolizumab

Other soft tissue sarcomas (including synovial sarcoma and malignant peripheral nerve sheath tumor

EXPERIMENTAL

Patients enrolled in the study will be treated initially with a 2 week run-in of lenvatinib 20 mg orally daily. Subsequently, they will start pembrolizumab 200 mg intravenously every 3 weeks (21-day cycles). Treatment will continue until progression or other indications for study withdrawal. Otherwise, treatment will be discontinued after a maximum of 35 cycles of pembrolizumab (approximately 2 years) or after achieving CR. RECIST v1.1 tumor assessments will be made at baseline (CT or MRI) and approximately every 3 cycles (or every 9 weeks +/- 1 week) for the first 9 cycles (27 weeks), then every 4 cycles (or every 12 weeks +/- 1week). Patients who progress after having discontinued therapy after completing 2 years of treatment or after achieving confirmed CR may be eligible to reinitiate therapy for an additional 1 year (approximately 17 cycles).

Drug: Lenvatinib; Drug: Pembrolizumab

Bone sarcomas (including osteosarcoma and chondrosarcoma)

EXPERIMENTAL

Patients enrolled in the study will be treated initially with a 2 week run-in of lenvatinib 20 mg orally daily. Subsequently, they will start pembrolizumab 200 mg intravenously every 3 weeks (21-day cycles). Treatment will continue until progression or other indications for study withdrawal. Otherwise, treatment will be discontinued after a maximum of 35 cycles of pembrolizumab (approximately 2 years) or after achieving CR. RECIST v1.1 tumor assessments will be made at baseline (CT or MRI) and approximately every 3 cycles (or every 9 weeks +/- 1 week) for the first 9 cycles (27 weeks), then every 4 cycles (or every 12 weeks +/- 1week). Patients who progress after having discontinued therapy after completing 2 years of treatment or after achieving confirmed CR may be eligible to reinitiate therapy for an additional 1 year (approximately 17 cycles).

Drug: Lenvatinib; Drug: Pembrolizumab

Interventions

Lenvatinib DRUG

20mg daily (two 10mg lenvatinib capsules) taken orally

Bone sarcomas (including osteosarcoma and chondrosarcoma); High grade undifferentiated pleomorphic sarcoma; Leiomyosarcoma; Other soft tissue sarcomas (including synovial sarcoma and malignant peripheral nerve sheath tumor; Vascular sarcomas (including angiosarcoma and epithelioid hemangioendothelioma)

Pembrolizumab DRUG

(200mg) will be administered as a 30-minute IV infusion, Q3W +/-3 days (infusions lasting between 25-40 minutes. Study treatment with pembrolizumab may be administered up to 3 days before or after the scheduled Day 1 of each cycle due to administrative reasons.

Bone sarcomas (including osteosarcoma and chondrosarcoma); High grade undifferentiated pleomorphic sarcoma; Leiomyosarcoma; Other soft tissue sarcomas (including synovial sarcoma and malignant peripheral nerve sheath tumor; Vascular sarcomas (including angiosarcoma and epithelioid hemangioendothelioma)

Eligibility Criteria

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

You may qualify if:

• Male or female age ≥18 years at time of informed consent
• Be willing and able to provide written informed consent/assent for the trial
• Be willing to comply with treatment protocol
• Availability of archival tissue for correlative studies; either a paraffin block or at least 20 unstained slides are acceptable
• Patients must have a metastatic and/or unresectable soft tissue sarcoma as below:
• Cohort A: Leiomyosarcoma
• Cohort B: High grade undifferentiated pleomorphic sarcoma
• Cohort C: Vascular sarcomas (including angiosarcoma and epithelioid hemangioendothelioma)
• Cohort D: Other soft tissue sarcomas (including synovial sarcoma and malignant peripheral nerve sheath tumor
• Cohort E: Bone sarcomas (including osteosarcoma and chondrosarcoma)
• Subjects must have had at least 1 but not more than 3 prior lines of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy); patients who decline the standard of care first-line systemic therapy will be eligible for this trial. Prior adjuvant therapy will not count provided it was completed more than 6-month previously.
• Presence of measurable disease per RECIST v1.1. Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment.Where and when possible, target lesions will not be chosen as the biopsy lesion.
• Must have a performance status ECOG 0-1.
• Screening laboratory values must meet the following criteria:
• Neutrophils ≥ 1000/μL

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 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 as screened by the Principal Investigator.
• Presence of any other concurrent malignancy requiring active therapy or thought to potentially interfere with the safe conduct or assessment of outcomes on this trial.
• History of allergy or intolerance to lenvatinib or study drug components (or any of their excipients) or severe (\> Grade 3) hypersensitivity reaction to pembrolizumab and/or any of its excipients or any monoclonal antibody.
• Prior use of lenvatinib or pazopanib 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 investigation drug or device (i.e., outside study treatment) during, or within 3 weeks of trial entry (time of initiation of experimental drug).
• Prior radiotherapy within 2 weeks of the start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Participants must have recovered all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy or alopecia may be eligible. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Clinically significant proteinuria:
• °Subjects having \>1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with proteinuria ≥/24-hour will be ineligible.
• Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
• ≥ Grade 3 gastrointestinal or non-gastrointestinal fistula
• New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months (baseline echocardiogram is not required unless clinically indicated) or left ventricular ejection fraction \<55% as determined by echocardiogram.
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• Parker Institute for Cancer Immunotherapy: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

lenvatinib; pembrolizumab

Study Officials

• Sujana Movva, MD

  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 pilot study evaluating the efficacy of lenvatinib plus pembrolizumab in the treatment of select metastatic and/or unresectable soft tissue sarcomas. Patients will be enrolled in one of five cohorts.

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: March 5, 2021
• Study Start: March 18, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (7)