Phase I/II Evaluation of a Cancer Lysate Vaccine and Montanide(R) ISA-51 VG With Entinostat and Nivolumab as Adjuvant Therapy Following Chemoradiation Therapy With or Without Surgery for Locally Advanced Esophageal Cancer

NCT05898828 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 10001544001544-C
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II study to determine the safety and immune response of the H1299 cell lysate vaccine mixed with Montanide(R) ISA-51 VG adjuvant, to be administered on the study in combination with Entinostat and Nivolumab in eligible participants with locally advanced esophageal cancers (EsC) following either neoadjuvant chemoradiation therapy (nCRT) or nCRT and surgery. Phase I of the protocol aims to determine the safe dose of the H1299 lung cancer cell lysate vaccine mixed with Montanide(R) ISA-51 VG adjuvant when it is administered in combination with Entinostat and Nivolumab. Phase II of the protocol will focus on assessing the level of immune response in participants receiving the study intervention when the H1299 cell lysate vaccine with Montanide(R) ISA-51 VG adjuvant is administered at the dose level determined in Phase I.

Conditions

Neoplasms; Esophageal Neoplasms; Esophagus Neoplasm; Esophagus Cancer; Neoplasms, Esophageal; Esophageal Cancer (EsC)

Keywords

Cell Mediated Response; immune subsets; peripheral immune subsets; CT antigens; neoadjuvant chemoradiation therapy (nCRT); H1299 Cell Lysates; EsC; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Phase I Component: To determine the safe dose of adjuvant H1299 lung cancer cell lysate vaccines with Montanide(R) ISA-51 VG administered in conjunction with entinostat and nivolumab in participants with locally advanced esophageal cancers (EsC)...

  Assessment of safety and tolerability as determined by the frequency and severity of adverse events

  before each cycle, every 2 weeks during Cycles 1 and 2 (AE only), at each treatment evaluation, and at the safety visit

• Phase II Component: To assess the frequency of immunologic responses to purified cancer-testis (CT) antigens in EsC participants receiving adjuvant vaccinations with H1299 cell lysate/Montanide(R) ISA-51 VG in combination with entinostat and niv...

  Assessment of immune response to CT antigens (new serologic reactivity or increase in existing antibody response to CT antigens, evidenced by IgM/IgG class switch or antibody titer)

  within 2 weeks prior to initiation of treatment, prior to 1st vaccination, 1 month following first 6 vaccinations, and every 6 months (24 weeks) during treatment continuation

Secondary Outcomes (3)

• Phase I Component: To assess the frequency of immunologic responses to purified cancer-testis (CT) antigens in EsC participants receiving adjuvant vaccinations with H1299 cell lysate/Montanide(R) ISA-51 VG in combination with entinostat and nivo...

  within 2 weeks prior to initiation of treatment, prior to 1st vaccine, one month following the first six vaccinations (start of cycle 7), and every 6 months (24 weeks) during treatment continuation

• Phase I + II Component: To assess safety of adjuvant H1299 lung cancer cell lysate vaccines with Montanide(R) ISA-51 VG administered in conjunction with entinostat and nivolumab in participants with locally advanced esophageal cancers (EsC) with...

  before each cycle, every 2 weeks between vaccines 1 and 2, at each treatment evaluation, and at the safety visit

• Phase II Component: To determine progression free survival (PFS) in EsC participants receiving the investigational adjuvant vaccine regimen

  every 12 weeks while on treatment or continued treatment, and during follow up every 3 months for 3 years, every 6 months for another 2 years or through disease progression ending at time of final PFS evaluation at 5 years post-enrollment

Study Arms (2)

1/ Phase I

EXPERIMENTAL

H1299 cell lysate vaccine with Montanide(R) ISA-51 VG, entinostat, and nivolumab (Phase I component to determine lysate dose)

Drug: Nivolumab; Drug: Entinostat; Biological: Montanide(R) ISA-51 VG Adjuvant; Biological: H1299 Cell Lysates

2/ Phase II

EXPERIMENTAL

H1299 cell lysate vaccine with Montanide(R) ISA-51 VG, entinostat, and nivolumab (lysate at dose determined in Phase I)

Drug: Nivolumab; Drug: Entinostat; Biological: Montanide(R) ISA-51 VG Adjuvant; Biological: H1299 Cell Lysates

Interventions

Nivolumab DRUG

Nivolumab 480 mg flat dose via intravenous infusion on Day 3 of every cycle starting at Cycle 2, for intended duration of 1 year.

1/ Phase I; 2/ Phase II

Entinostat DRUG

Entinostat (5 mg) self-administered on Days -14 and -7 prior to the first vaccination cycle, then entinostat (3 mg) self-administered on Days 1, 8, 15, and 22 of each vaccine cycle (Cycles 1-6). Entinostat continuation for subjects with immunologic response and NED during additional 2 vaccine injections.

1/ Phase I; 2/ Phase II

Montanide(R) ISA-51 VG Adjuvant BIOLOGICAL

H1299 cell lysate with Montanide(R) ISA-51 VG adjuvant vaccine via subcutaneous injections once every cycle (1 cycle=28 days) for 6 cycles (i.e., 6 vaccinations). Dose Level 1 (DL1) starting dose is 20 mg lysate protein in 2-2.5 mL Montanide(R) ISA-51 VG adjuvant; lysate concentration will be 8-10 mg/mL. Additional 2 vaccine injections for subjects with immunologic response and NED.

1/ Phase I; 2/ Phase II

H1299 Cell Lysates BIOLOGICAL

H1299 cell lysate with Montanide(R) ISA-51 VG adjuvant vaccine via subcutaneous injections once every cycle (1 cycle=28 days) for 6 cycles (i.e., 6 vaccinations). Dose Level 1 (DL1) starting dose is 20 mg lysate protein in 2-2.5 mL Montanide(R) ISA-51 VG adjuvant; lysate concentration will be 8-10 mg/mL. Additional 2 vaccine injections for subjects with immunologic response and NED.

1/ Phase I; 2/ Phase II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with clinical Stage II (T2/N0-N1; T3/N0) or Stage III (T1-T2/N2, T3/N1-N2) EsC per 8th edition TNM Staging System who have histologically documented or suspected residual disease in the esophagus or regional nodes following nCRT. Diagnosis must be confirmed by the NIH Laboratory of Pathology.
• No prior anti-PD1/anti-PD-L1 therapy for their EsC.
• Participant must be enrolled within 16 weeks following completion of nCRT or nCRT/surgery
• ECOG performance status of 0-1.
• years of age or older
• Participant must be willing to co-enroll on 06C0014 (Prospective Analysis of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies) allowing for the use of tumor or normal tissues for correlative experiments pertaining to this protocol and related translational research efforts in the Thoracic Surgery Branch (TSB).
• Adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters (all eligibility assessment/enrollment bloodwork must be done at NIH no more than 2 weeks prior to initiation of study therapy):
• Absolute neutrophil count greater than 1500/mm\^3
• Platelet count greater than 100,000/mm\^3
• Hemoglobin greater than 8 g/dL (participants may receive transfusions to meet this parameter)
• INR \<= 1.5 x ULN
• Total bilirubin \<1.5 x upper limits of normal (except those with Gilberts disease)
• Serum creatinine less than or equal to 1.6 mg/mL or the eGFR (calculated per institutional standards) must be greater than 60 mL/min/1.73m\^2
• Oxygen saturation equal to or greater than 92% on room air within 2 weeks of initiation of study therapy.
• Seronegative for HIV antibody by bloodwork performed at NIH no more than 4 weeks prior to initiation of study therapy.

You may not qualify if:

• Participants who are receiving any other investigational agents
• Participants with a history of pneumonitis will be excluded unless cleared by Pulmonary Medicine consultants
• Participants requiring chronic systemic treatment with steroids above physiologic doses.
• Participants receiving warfarin anticoagulation, who cannot be transitioned to other agents such as enoxaparin or dabigatran, and for whom anticoagulants cannot be held for up to 24 hours.
• Participants with uncontrolled hypertension (\>160/95) at screening, unstable coronary disease evidenced by EKG evidence of cardiac ischemia or uncontrolled arrhythmias, unstable angina, decompensated CHF (\>NYHA Class II), or myocardial infarction within 6 months prior to initiation of study therapy.
• Participants with any of the following pulmonary function abnormalities: FEV, \< 35% predicted; DLCO \< 35% predicted (post-bronchodilator); based on assessment performed no more than 4 weeks prior to initiation of study therapy.
• Participant pregnancy.
• Other malignancy requiring treatment with the exception of localized skin cancer amenable to topical therapies
• Uncontrolled intercurrent illness occurring within 3 months prior to initiation of study therapy that would limit compliance with study requirements. Intercurrent illness may include any conditions uncovered during screening assessments (physical examination, laboratory assessments, etc.) that, in the judgment of the investigator, precludes participation because it could present disproportionate risk to the participant

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neoplasms; Esophageal Neoplasms

Interventions

Nivolumab; entinostat

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal 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

• David S Schrump, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2023
• First Posted: June 12, 2023
• Study Start: August 2, 2024
• Primary Completion: August 2, 2024
• Study Completion: August 2, 2024
• Last Updated: August 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers after the trial has been completed and closed.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)