Phase II Trial of Pembrolizumab Plus Lenvatinib in Advanced Adrenal Cortical Carcinoma

NCT05036434 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: MCT-STRC-02
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

• Clinical Indication : Advanced adrenal cortical carcinoma after platinum-based chemotherapy
• Trial Type : Single arm, prospective trial
• Route of administration : Intravenous (pembrolizumab) and peroral (lenvatinib)
• Treatment Groups : Single arm
• Number of trial participants : 30

Conditions

Adrenocortical Carcinoma

Outcome Measures

Primary Outcomes (1)

• To assess the antitumor activity of pembrolizumab plus lenvatinib in patients with advanced ACC.

  Through study completion, an average of 1 year.

  Treatment-Related Adverse Events as Assessed by CTCAE v4.0, Imaging assessment by RECIST v1.1.

Study Arms (1)

Treatment arm

EXPERIMENTAL

Pembrolizumab 200mg q 3wks IV / Lenvatinib 20mg daily once PO q 3wks

Drug: Pembrolizumab / Lenvatinib

Interventions

Pembrolizumab / Lenvatinib DRUG

Pembrolizumab Plus Lenvatinib administration.

Also known as: Keytruda / Lenvima

Treatment arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 19 years of age on the day of signing informed consent with histologically confirmed diagnosis of adrenal cortical carcinoma will be enrolled in this study.
• Patients with locally advanced, recurrent, or metastatic disease not amenable to surgery, radiotherapy, or combined modality therapy with curative intent.
• Patients who have received prior systemic therapy including combined mitotane and cisplatin-based chemotherapy as a palliative aim systemic therapy in advanced setting, and have had disease progression within 6 months of the last dose of the most recent systemic therapy. Patients who discontinued prior therapy due to intolerable toxicities can be included.
• \*However, patients who have not received prior mitotane therapy due to inability to import mitotane domestically who disease has progression may be exceptionally eligible for registration.
• Patients should have measurable disease according to RECIST v1.1 meeting the following criteria:
• at least 1 lesion of ≥10 mm in the longest diameter for a non-lymph node or ≥15 mm in the short-axis diameter for a lymph node that is serially measurable according to RECIST using CT or MRI
• lesions that have had external beam radiotherapy or other loco-regoinal therapies such as radiofrequency ablastion must show subsequent evidence of substantial size increase to be deemed a target lesion.
• Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1
• Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP≤150/90 mmHg at screening and no change in hypertensive medications within 1 week prior to the cycle 1 day 1.
• Adequate renal function defined as creatinine ≤1.5 times the upper limit of normal (×ULN) or calculated creatinine clearance ≥30 ml/min per the Cockcroft and Gault formula
• Adequate bone marrow function:
• Absolute neutrophil count (ANC)≥1500/mm3 (≥1.5×103/μL)
• platelets≥100,000/ mm3 (≥100×109/L)
• hemoglobin≥9.0 g/dL
• adequate blood coagulation function defined by international Normlized Ratio (INR)≤1.5 unless participant is receiving anticoagulation therapy

You may not qualify if:

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior therapy with any VEGFR TKI or monoclonal antibody targeting VEGF pathway.
• Has received major surgery within 2 weeks of start of study intervention. Participants must have recovered from any toxicity and/or complications from major surgery prior to starting therapy.
• Previous radiotherapy to the only measurable lesion: but previous radiotherapy will be permitted unless the lesion is the only measurable lesion.
• Subjects having \>1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥1g/24-hour will be ineligible.
• Gastrointestinal malabsorption, gastrointestinal obstruction, or any other condition that might affect the absorption of lenvatinib.
• Significant cardiovascular impairment within 6 months of the first dose of study drug. History of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke, cardiac arrhythmia associated with significant cardiovascular impairment, or a left ventricular ejection fracture (LVEF) below the institutional normal range as determined by MUGA or echocardiogram.
• Prolongation of QTc interval to \>480 msec
• Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. 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.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• 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. The use of physiologic doses of corticosteroids may be approved at the discretion of treating physician. In mitotane treated subject, adrenal insufficiency happens inevitably and required dose of corticosteroid is higher than usual due to altered metabolism of corticosteroid.48 Therefore, the decision on whether the dose of maintenance corticosteroid is acceptable for enrollment depends on investigator.
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Clinically insignificant or curatively treated localized prostate cancer and curatively treated thyroid cancer of any stage can be included at the discretion of treating physician.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically 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 first dose of study intervention.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.

Sponsors & Collaborators

• MSD Korea Ltd.: collaborator
• National Cancer Center, Korea: lead

Study Sites (1)

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Study Officials

• Tak Yun

  National Cancer Center, Republic of Korea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor of Medicine

Study Record Dates

• First Submitted: August 26, 2021
• First Posted: September 5, 2021
• Study Start: November 15, 2021
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

KR (1)