This phase II trial tests whether elraglusib and carboplatin work to shrink tumors in patients with salivary gland cancer that has come back (recurrent), cannot be removed by surgery (unresectable), or has spread to other places in the body (advanced/metastatic). Elraglusib blocks a protein called glycogen synthase kinase-3 beta (GSK-3beta) which is thought to be important in signaling cancer growth and to have immune properties. By blocking the action of GSK-3beta protein, elraglusib may block other cancer signals downstream and slow cancer cell growth. Chemotherapy drugs, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving elraglusib with carboplatin with or without pembrolizumab may help delay the progression of salivary cancer and improve outcomes.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05010629.
PRIMARY OBJECTIVE:
I. To estimate overall response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 from the date of study registration.
SECONDARY OBJECTIVES:
I. To estimate progression frees survival (PFS) from date of study registration.
II. To estimate overall survival (OS) from date of study registration.
III. To estimate duration of therapeutic response, and response among patients in part 1 and part 2, and among all cohorts individually.
IV. To evaluate safety and toxicity (Common Terminology Criteria for Adverse Events [CTCAE] v5.0).
V. To measure quality of life metrics on study treatment (University of Washington Quality of Life Questionnaire [UW-QOL]).
VI. To correlate molecular and immunologic parameters with response and survival outcomes.
OUTLINE:
PART I (NO IMMUNOTHERAPY): Patients receive carboplatin intravenously (IV) or cisplatin IV on day 1 and elraglusib IV on days 1 and 4. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy during screening and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.
PART II (IMMUNOTHERAPY): Patients receive pembrolizumab IV on day 1 for 2 cycles and then receive the same carboplatin or cisplatin and elraglusib regimen as part I for cycles 3 and beyond. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy during screening and CT or MRI throughout the study.
After completion of study treatment, patients are followed up every 9-12 weeks for up to 3 years from time of study enrollment.
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorGlenn J. Hanna
