Selective HDAC6 Inhibitor ACY-241 in Combination With Ipilimumab and Nivolumab

NCT02935790 | Completed Phase 1

• 1 other identifier: ACE-ST-204
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Determine the safety, tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of ACY-241 in combination with ipilimumab and nivolumab in patients with unresectable Stage III/Stage IV melanoma.

Conditions

Malignant Melanoma

Keywords

unresectable; melanoma

Outcome Measures

Primary Outcomes (1)

• Number of Dose Limiting Toxicities defining the MTD

  12 months

Secondary Outcomes (4)

• Percentage of Patients with ORR based on RECIST 1.1 change from baseline by CT or MRI measurements

  12 months

• Percentage of Patients with ORR based on irRC change from baseline by CT or MRI measurements

  12 months

• Maximum observed concentration (Cmax) of ACY-241 administered in combination with ipilimumab and nivolumab

  12 months

• trough concentrations of ACY-241 administered in combination with ipilimumab and nivolumab

  12 months

Other Outcomes (1)

• Exploratory: Pharmacodynamic changes in biomarkers (to be determined) pre-dose versus post-dose in peripheral blood and tumor tissue

  12 months

Study Arms (1)

ACY-241 combo with Ipi and Nivo

EXPERIMENTAL

ACY-241 in Combination with Ipilimumab and Nivolumab

Drug: ACY-241; Drug: nivolumab; Drug: ipilimumab

Interventions

ACY-241 DRUG

tablet

Also known as: HDAC6 Inhibitor

ACY-241 combo with Ipi and Nivo

nivolumab DRUG

infusion

Also known as: OPDIVO

ACY-241 combo with Ipi and Nivo

ipilimumab DRUG

infusion

Also known as: YERVOY

ACY-241 combo with Ipi and Nivo

Eligibility Criteria

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

You may qualify if:

• Patients must have signed and dated an Institutional Review Board/Independent Ethics Committee -approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study.
• All patients must be either Stage IIIb/c or Stage IV according to the American Joint Committee on Cancer (AJCC) (7th edition) and have histologically-confirmed melanoma that is felt to be surgically unresectable in order to be eligible. Please refer to the AJCC Cancer Staging Manual, 7th edition for a description of tumor, lymph node, metastasis and staging.
• All melanomas, except ocular/uveal melanoma, regardless of primary site of disease will be allowed; mucosal melanomas are eligible.
• Patients must not have received prior anticancer treatment for metastatic disease (for example, but not limited to, systemic, local, radiation, radiopharmaceutical).
• All patients must have their disease status documented by a complete physical examination and imaging studies within 4 weeks prior to the first dose of study drug. Imaging studies must include computerized tomography (CT) scan of neck, chest, abdomen, pelvis, and all known sites of resected disease in the setting of Stage IIIb/c or Stage IV disease, and brain magnetic resonance imaging (\[MRI\], brain CT allowable if MRI is contraindicated).
• The complete set of baseline radiographic images must be available before treatment initiation.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Tumor tissue from the resected site of disease must be provided for biomarker analyses
• Prior treated CNS metastases must be without MRI evidence of recurrence for at least 4 weeks after treatment. Patients must be off immunosuppressive doses of systemic steroids (≥ 10 mg/day prednisone or equivalent) for at least 14 days prior to study drug administration, and must have returned to neurologic baseline status postoperatively.
• The 4-week period of stability is measured after the completion of the neurologic interventions (ie, surgery and/or radiation).
• In addition to neurosurgery to treat CNS metastases, adjuvant radiation after the resection of CNS metastasis is allowed. Immunosuppressive doses of systemic steroids (doses ≥ 10 mg/day prednisone or equivalent) must be discontinued at least 14 days before study drug administration.
• Prior surgery that required general anesthesia must be completed at least 4 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration.
• All baseline laboratory requirements will be assessed and should be obtained within 14 days of first dose of study drug. Screening laboratory values must meet the following criteria:
• White blood cells ≥ 2000/µL

You may not qualify if:

• Patients with carcinomatosis meningitis or a history of ocular/uveal melanoma are excluded.
• Patients with previous nonmelanoma malignancies are excluded unless a complete resection or remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period (exceptions include, but are not limited to, nonmelanoma skin cancers, in situ bladder cancer, in situ gastric cancer or gastrointestinal stromal tumor, in situ colon cancers, in situ cervical cancers/dysplasia, or breast carcinoma in situ).
• Patients with active, known, or suspected autoimmune disease. Patients with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the Principal Investigator be consulted prior to signing informed consent.
• Patients with a condition requiring systemic treatment with either corticosteroids (≥ 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
• Prior therapy for melanoma with the following exceptions which are allowed: 1) surgery for the melanoma lesion(s), 2) adjuvant RT after neurosurgical resection for CNS lesions, and 3) prior adjuvant IFN (see qualifier below). Specifically, patients who received prior therapy with anti-PD-1, anti PD L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell costimulation or checkpoint pathways) are not eligible.
• Prior treatment with adjuvant IFN is allowed if completed ≥ 3 months prior to treatment.
• Treatment directed against the melanoma (eg, chemotherapy, targeted agents, biotherapy, limb perfusion) that is administered after a prior complete resection other than adjuvant radiation after neurosurgical resection and IFN for resected melanoma.
• Previous therapy with histone deacetylase inhibitor.
• 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 × ULN
• AST or ALT \> 2.5 × ULN. For patients with liver metastasis, AST or ALT \> 5 × ULN

Sponsors & Collaborators

• Celgene: lead
• Syneos Health: collaborator
• ApoCell, Inc.: collaborator
• Celerion: collaborator
• NYU Langone Health: collaborator

Study Sites (1)

NYU Langone Medical Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

citarinostat; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jeffrey S Weber

  Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center

  PRINCIPAL INVESTIGATOR

• Elizabeth Buchbinder

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: October 18, 2016
• Study Start: September 30, 2016
• Primary Completion: April 7, 2017
• Study Completion: April 7, 2017
• Last Updated: August 24, 2017

Record last verified: 2017-08

Locations

US (1)