Pembrolizumab and Sunitinib Malate in Treating Participants With Refractory Metastatic or Unresectable Thymic Cancer

Study of Investigational Medications for Thymic Cancer

P
Patrick Loehrer, MD

Primary Investigator

Administratively Closed
18 years or above
All
Phase 2
40 participants needed
1 Location

Brief description of study

This phase II trial studies how well pembrolizumab and sunitinib malate work in treatingwith thymic cancer that has spread to other places in the body or cannot beved by surgery and does not respond to treatment. Monoclonal antibodies, such asbrolizumab, may interfere with the ability of tumor cells to grow and spread. Sunitiniby stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and sunitinib malate may work better in treating thymic cancer.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:

IU Clinical Trials Office 

Email: iutrials@iu.edu 

Phone: (317) 278-5632

Detailed description of study

PRIMARY OBJECTIVES:
I. To evaluate the efficacy of pembrolizumab and sunitinib malate (sunitinib) for thewith thymic carcinoma that have progressed on prior platinum basedhemotherapy as measured by objective response rate.
SECONDARY OBJECTIVES:
I. To evaluate the safety profile and toxicity of combination pembrolizumab and sunitinibCommon Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0.
II. To evaluate the progression free survival (PFS) and overall survival (OS) of patientsd with combination pembrolizumab and sunitinib.
EXPLORATORY OBJECTIVES:
I. To determine objective response rate (ORR), PFS, and OS by PD-L1 expression > 50% tumor(TPS) (by 22C3 assay) II. To determine whether sunitinib treatment leads toPD-L1 expression and tumor infiltrating lymphocytes and decrease inyeloid-derived suppressor cells (MDSC) in both tumor and peripheral blood.

TLINE

Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and sunitiniby (PO) daily on days 1-14. Courses repeat every 21 days for 24 months in thebsence of disease progression or unacceptable toxicity.
After completion of the study treatment, participants are followed up for 30 days, every 6 weeks for 1 year, and every 9 or 12 weeks thereafter.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Thymic Carcinoma, Cancer
  • Age: 18 years or above
  • Gender: All

Inclusion Criteria:
  • Be willing and able to provide written informed consent/assent for the trial
  • Have histologically or cytologically-documented diagnosis of advanced (metastaticd/or unresectable) thymic carcinoma, for which no curative treatment (includingurgery, radiation, or other) is available
  • Have experienced progressive disease after at least one previous regimen ofum-based chemotherapy
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)1.1
  • Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block;y obtained archival FFPE tumor tissue block (if an FFPE tissue block cannotbe provided, 15 unstained slides [10 minimum] will be acceptable) from a primary orumor resection or biopsy can be provided if it was obtained within 3 yearsg; patients with tumor specimens older than 3 years may still begible if deemed so by study sponsor
  • Be willing to provide tissue from an on-treatment fine-needle aspiration (FNA) or corebiopsy of a tumor lesion; subjects must consent to on-treatment biopsy prior tohowever in subjects for whom newly-obtained samplesbe provided (e.g. inaccessible or subject safety concern) may still continue onudy
  • Be willing to provide peripheral blood samples at screening and day 1 of cycle 2 andycle 3 for correlative studies
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
  • Life expectancy greater than 3 months
  • Ability to swallow and retain oral medication
  • No evidence of uncontrolled hypertension as documented by 2 baseline blood pressure(BP) readings taken at least 1 hour apart; the baseline systolic BP readings must be=< 140 mm Hg, and the baseline diastolic BP readings must be =< 90 mm Hg; use ofhypertensive medications to control BP is allowed
  • Left ventricular ejection fraction (LVEF) >= lower limit of normal (LLN) as assessedby either multigated acquisition (MUGA) scan or echocardiogram (ECHO)
  • Absolute neutrophil count (ANC) >= 1,500 /mcL, performed within 28 days of treatment
  • Platelets >= 100,000 / mcL, performed within 28 days of treatment initiation
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated(glomerular filtration rate [GFR] can also be used in place ofCrCl) >= 60 mL/min for subject with creatinine levels > 1.5 Xutional ULN, performed within 28 days of treatment initiation
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with totalbilirubin levels > 1.5 ULN, performed within 28 days of treatment initiation
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and(ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 XLN OR =< 5 X ULN for subjects with liver metastases, performed within 28 days of
  • Albumin >= 2.5 mg/dL, performed within 28 days of treatment initiation
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unlessubject is receiving anticoagulant therapy as long as PT or partial thromboplastin(PTT) is within therapeutic range of intended use of anticoagulants, performedwithin 28 days of treatment initiation
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receivinggulant therapy as long as PT or PTT is within therapeutic range of intended usegulants, performed within 28 days of treatment initiation
  • Female subject of childbearing potential should have a negative urine or serumgnancy within 72 hours prior to receiving the first dose of study medication; ifhe urine test is positive or cannot be confirmed as negative, a serum pregnancy testwill be required
  • Female subjects of childbearing potential must be willing to use an adequate method ofhe course of the study through 120 days after the last dose ofudy medication
    • Note: abstinence is acceptable if this is the usual lifestyle and preferredhe subject

  • Male subjects of childbearing potential must agree to use an adequate method of

    contraception starting with the first dose of study therapy through 120 days after thedose of study therapy
    • Note: abstinence is acceptable if this is the usual lifestyle and preferredhe subject
Exclusion Criteria:
  • Is currently participating and receiving study therapy or has participated in a studyvestigational agent and received study therapy or used an investigationaldevice within 4 weeks of the first dose of treatment
  • Has received prior sunitinib or pembrolizumab therapy for the treatment of malignancy
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or anyher form of immunosuppressive therapy within 7 days prior to the first dose of trial
  • Has a known history of active tuberculosis (TB) (Bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or sunitinib or any of their excipients
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapywithin 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or atbaseline) from adverse events due to a previously administered agent
    • Note: subjects with =< grade 2 neuropathy due to chemotherapy are an exception tohis criterion and may qualify for the study
    • Note: if subject received major surgery, they must have recovered adequately fromhe toxicity and/or complications from the intervention prior to starting therapy

  • Has a known additional malignancy that is progressing or requires active treatment;

    exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of thekin that has undergone potentially curative therapy or in situ cervical cancer
  • Has known active central nervous system (CNS) metastases and/or carcinomatousgitis; subjects with previously treated brain metastases may participate providedhey are stable (without evidence of progression by imaging for at least four weekshe first dose of trial treatment and any neurologic symptoms have returnedbaseline), have no evidence of new or enlarging brain metastases, and are not usingds for at least 7 days prior to trial treatment; this exception does not includeus meningitis which is excluded regardless of clinical stability
  • Has active autoimmune disease, including myasthenic syndrome, which has requiredystemic treatment in the past 2 years (i.e. with use of disease modifying agents,ds or immunosuppressive drugs); replacement therapy (eg., thyroxine,ulin, or physiologic corticosteroid replacement therapy for adrenal or pituitaryufficiency, etc.) is not considered a form of systemic treatment
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormalityhat might confound the results of the trial, interfere with the subject?she full duration of the trial, or is not in the best interest ofhe subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere withwith the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within thejected duration of the trial, starting with the pre-screening or screening visithrough 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) orhepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] isdetected)
  • Has received a live vaccine within 30 days of planned start of study therapy
    • Note: seasonal influenza vaccines for injection are generally inactivated fluvaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist)ve attenuated vaccines, and are not allowed
  • Significant proteinuria at baseline (> 500 mg/ 24 h, or > 2+ on spot analysis)
  • Serious non-healing wound, ulcer or bone fracture
  • Evidence of bleeding diathesis or coagulopathy
  • Grade >= 3 hemorrhage within 4 weeks of patient randomization
  • Recent (< 6 months) arterial thromboembolic events, including transient ischemick, cerebrovascular accident, unstable angina, or myocardial infarction
  • Ongoing cardiac dysrhythmias of National Cancer Institute (NCI) CTCAE grade >= 2 orgation of the corrected QT interval (QTc) interval to > 500 msec
  • Current use or anticipated need for treatment with drugs or foods that are knowng CYP3A4/5 inhibitors, including their administration within 10 days prior towith study drug (eg, grapefruit juice orgrapefruit/grapefruit-related citrus fruits [eg, Seville oranges, pomelos],ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin,ythromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir,vir nefazodone, lopinavir, troleandomycin, mibefradil, and conivaptan); theuse of these medications (if applicable), such as 2% ketoconazole cream, iswed
  • Current use or anticipated need for drugs that are known strong CYP3A4/5 inducers,uding their administration within 10 days prior to patient randomization, eg,henobarbital, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin, clevidipine,John?s wort
  • Any condition which in the investigator?s opinion deems the participant an unsuitabledidate to receive study drug

This study investigates treatments for thymic cancer that has spread or cannot be removed by surgery. Thymic cancer is a rare type of cancer that occurs in the thymus, a small organ in the upper chest. The study focuses on using investigational medications to see how well they work in stopping the growth of cancer cells.

Participants will receive an investigational medication intravenously and another one orally. The intravenous medication is given over 30 minutes, and the oral medication is taken daily for two weeks. This cycle repeats every three weeks for up to two years, as long as there are no serious side effects or the cancer does not get worse.

  • Who can participate: Adults aged 18 and older with advanced thymic cancer that cannot be cured with surgery or other treatments can participate. They must have previously tried chemotherapy and have a life expectancy of more than three months.
  • Study details: Participants will receive an investigational medication intravenously and another orally. The intravenous medication is administered over 30 minutes, and the oral medication is taken daily for two weeks. This cycle repeats every three weeks for up to two years, as long as there are no serious side effects or the cancer does not progress. A placebo is not used in this study.
  • Study timelines: The study will last 24 months.
Updated on 10 Mar 2026. Study ID: CTO-OSU17234, 15099, 10724

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