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Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies | Clinical Trials | Clareo Health

COMPLETEDPHASE1

Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies

A Phase 1b Dose Escalation/Expansion Study of Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies

NCT03590054•Rahul Aggarwal

View on ClinicalTrials.gov

Summary

This phase I trial studies the best dose and side effects of abexinostat and how well it works with given together with pembrolizumab in treating participants with microsatellite instability (MSI) solid tumors that have spread to other places in the body. Abexinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving abexinostat and pembrolizumab may work better in treating participants with solid tumors.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the maximally tolerated and recommended phase 2 dose of abexinostat in combination with anti-PD-1/PD-L1 checkpoint inhibitor (CPI). (Dose escalation) II. To determine the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients treated with abexinostat in combination with CPI in patients with prior primary (cohort A) or acquired (cohort B) resistance to prior CPI treatment. (Dose expansion) SECONDARY OBJECTIVES: I. To determine the objective response rate and median duration of response (DoR) by immune modified (i)RECIST criteria. II. To determine the median progression-free survival (PFS). III. To further characterize the safety profile of the treatment combination. OUTLINE: This is a dose-escalation study of abexinostat. Participants receive abexinostat orally (PO) twice daily (BID) on days 1-21 and pembrolizumab intravenously (IV) on over 30 minutes day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up for 90 days.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patient \>= 18 years of age at the time of study enrollment.
•Has histologically confirmed locally advanced or metastatic solid tumor malignancy with one of the following tumor types:
•* Urothelial carcinoma
•* Melanoma
•* Non-small cell lung cancer
•* Small cell lung cancer
•* Non-pulmonary squamous cell carcinoma
•* Head and neck squamous cell carcinoma
•* MSI-high solid tumor, with MSI-high status defined by microsatellite instability testing by Polymerase chain reaction (PCR), loss of mismatch repair proteins by Immunohistochemistry (IHC), or Clinical Laboratory Improvement Amendments (CLIA)-approved next generation sequencing test.
•* Gastric and gastro-esophageal junction adenocarcinoma
+22 more criteria

Exclusion Criteria

•Has persistent clinically significant toxicities (grade \>= 2; per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5) from previous anticancer therapy (excluding alopecia which is permitted and excluding grades 2 and 3 laboratory abnormalities if they are not associated with symptoms, are not considered clinically significant by the Investigator, and can be managed with available medical therapies).
•Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/ interstitial lung disease
•Has a diagnosis of clinically significant immunodeficiency.
•Has received external-beam radiation or another systemic anticancer therapy within 14 days or 5 half-lives (whichever is shorter) before start of study treatment.
•Has received treatment with an investigational drug or monoclonal antibody within 28 days prior to study treatment administration. For classes of investigational agents that are not known to have prolonged toxicities, the washout time may be decreased to 14 days at the discretion of the principal investigator.
•Has received previous treatment with a histone deacetylase (HDAC) inhibitor.
•Has an additional active malignancy that may confound the assessment of the study endpoints. Patients with the following concomitant neoplastic diagnoses are eligible: nonmelanoma skin cancer and carcinoma in situ including transitional cell carcinoma, anal carcinoma, and melanoma in situ).
•Has clinically significant cardiovascular disease including, but not limited to:
•* Uncontrolled or any New York Heart Association class 3 or 4 congestive heart failure
•* Uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months before study entry
+14 more criteria

Locations (1)

University of California, San Francisco

San Francisco, California, United States

Key Dates

Start Date

August 20, 2018

Primary Completion Date

November 30, 2023

Completion Date

November 30, 2023

Last Updated

March 22, 2024

Enrollment

ACTUAL participants

Conditions

Stage III Cutaneous MelanomaStage IV Cutaneous MelanomaLocally Advanced MelanomaLocally Advanced Solid NeoplasmMetastatic Head and Neck Squamous Cell CarcinomaMetastatic Malignant Solid NeoplasmMetastatic MelanomaMetastatic Urothelial CarcinomaNon-Small Cell Lung CarcinomaStage IB Lung Cancer AJCC v7Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8Stage III Lung Cancer AJCC v8Stage III Ureter Cancer AJCC v8Stage IIIA Lung Cancer AJCC v8Stage IIIB Lung Cancer AJCC v8Stage IIIC Lung Cancer AJCC v8Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8Stage IV Lung Cancer AJCC v8Stage IV Ureter Cancer AJCC v8Stage IVA Lung Cancer AJCC v8Stage IVB Lung Cancer AJCC v8

Interventions

Abexinostat

DRUG

Pembrolizumab

BIOLOGICAL

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RECRUITINGPHASE1

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 22, 2024Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies

Inclusion Criteria

Exclusion Criteria

IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors

A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing

Ketogenic Dietary Intervention to Improve Response to Immunotherapy in Patients With Metastatic Melanoma and Metastatic Kidney Cancer

Time-of-Day Specified Immunotherapy for Advanced Melanoma, The TIME Trial

Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma

A Study to Compare the Administration of Pembrolizumab After Surgery Versus Administration Both Before and After Surgery for High-Risk Melanoma