Selective HDAC6 Inhibitor ACY 241 in Combination With Nivolumab in Patients With Unresectable Non Small Cell Lung Cancer

A Phase 1b Study of the Selective HDAC6 Inhibitor ACY-241 in Combination With Nivolumab in Patients With Unresectable Non-Small Cell Lung Cancer

Determine the safety, tolerability, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of ACY 241 in combination with nivolumab.

Study Overview

• Status: Terminated
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Nivolumab; Drug: ACY-241

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 350

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Must be able to understand and voluntarily sign an informed consent form (ICF).
2. Must be ≥ 18 years of age at the time of signing the ICF.
3. Must be able to adhere to the study visit schedule and other protocol requirements.
4. Patients must have histologically confirmed unresectable NSCLC for which nivolumab is clinically appropriate. Patients must have had one line of prior therapy and have progressed or have discontinued due to toxicity.
5. Measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and Immune related Response Criteria (irRC).
6. Life expectancy > 12 weeks.
7. Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
8. Willingness to have pre treatment and on treatment tumor biopsies.
9. Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Female patients of childbearing potential must agree to use adequate contraceptive measures until 3 months after the last study drug is taken. Females of childbearing potential must have a negative pregnancy test. It is not known if the antideacetylase activity of this experimental drug may be harmful to the developing fetus or nursing infant.
10. Male patients should be willing to use barrier contraceptive (ie, condoms) until 3 months after last study drug is taken.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from giving informed consent.
2. Any serious concurrent medical conditions, laboratory abnormality, or psychiatric illness that might make the patient nonevaluable, put the patient's safety at risk, or prevent the patient from following the study requirements.
3. Pregnant or lactating females.
4. Patients with uncontrolled brain metastases. Existing brain metastases must have been previously treated and currently stable.
5. Patients who have had chemotherapy within 14 days before entering the study or those who have not recovered from AEs to ≤ Grade 1 due to agents administered more than 14 days earlier.
6. Previous therapy with histone deacetylase (HDAC) inhibitor and/or anti PD 1, anti PD L1, or anti CTLA4 immunotherapy.

7. Any of the following laboratory abnormalities:

   • ANC < 1,500/µL
   • Platelet count < 100,000/µL
   • Hematologic growth factors are not allowed at Screening or during the first cycle of treatment
   • Hemoglobin < 9 g/dL (< 5.5 mmol/L; previous red blood cell transfusion is permitted)
   • Creatinine > 1.5 × upper limit of normal (ULN)
   • AST or ALT > 2.5 × ULN. For patients with liver metastasis AST or ALT > 5 × ULN
   • Serum total bilirubin > 1.5 mg/dL or > 3 × ULN for patients with hereditary benign hyperbilirubinemia
8. Corrected QT interval (QTc) using Fridericia's formula (QTcF) value > 480 msec at Screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at Screening; previous history of drug induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG).
9. Congestive heart failure (New York Heart Association Class III or IV), myocardial infarction within 12 months before starting study treatment, or unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.
10. Patients with chronic autoimmune disease(s) requiring systemic immunosuppression.
11. Positive human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infection.
12. Patients who received any of the following within the 14 days before initiating study treatment: major surgery, radiation therapy, and/or systemic therapy (standard or an investigational or biological anticancer agent).
13. Current enrollment in another clinical study involving treatment and/or is receiving an investigational agent for any reason, or use of any investigational agents within 14 days of initiating study treatment.
14. Incidence of gastrointestinal disease that may significantly alter the absorption of ACY 241.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACY-241 in combination with nivolumab	Drug: Nivolumab; Specified dose on specified days; Other Names: Opdivo; Drug: ACY-241; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	one to two years
recommended Phase 2 dose (RP2D) of ACY 241 in combination with nivolumab	one to two years

Secondary Outcome Measures

Outcome Measure	Time Frame
preliminary antitumor activity of ACY 241 in combination with nivolumab	one to two years
Maximum Plasma Concentration [Cmax] of ACY 241 in combination with nivolumab on biomarkers in peripheral blood and tumor tissue	one to two years

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Ileana Elias, MD, Celgene

Publications and helpful links

General Publications

• Awad MM, Le Bruchec Y, Lu B, Ye J, Miller J, Lizotte PH, Cavanaugh ME, Rode AJ, Dumitru CD, Spira A. Selective Histone Deacetylase Inhibitor ACY-241 (Citarinostat) Plus Nivolumab in Advanced Non-Small Cell Lung Cancer: Results From a Phase Ib Study. Front Oncol. 2021 Sep 6;11:696512. doi: 10.3389/fonc.2021.696512. eCollection 2021. Erratum In: Front Oncol. 2022 Jun 07;12:889996.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2016
• Primary Completion (Actual): January 22, 2024
• Study Completion (Actual): January 22, 2024

Study Registration Dates

• First Submitted: December 14, 2015
• First Submitted That Met QC Criteria: December 16, 2015
• First Posted (Estimated): December 18, 2015

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: ACE-ST-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No