A Phase I Study of CYT001

JRCT ID: jRCT2031190072

Registered date:08/08/2019

Basic Information

• Recruitment status: Suspended
• Health condition(s) or Problem(s) studied: Hepatocellular carcinoma
• Date of first enrollment: 01/05/2020
• Target sample size: 6
• Study type: Interventional
• Intervention(s): Reconstitute two kinds of cancer peptide vaccines (HSP70 derived peptide and GPC3 derived peptide) by injecting the adjuvants (hLAG-3Ig and Poly-ICLC)

Outcome(s)

• Primary Outcome: Incidence of Dose-limiting toxicities (DLT)

Secondary Outcome

Safety:
Incidence of Adverse events (AEs) and changes in laboratory values, vital signs, body weight, ECOG PS, 12-lead electrocardiogram and chest X-ray
Efficacy:
Overall Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS), Tumor Shrinkage Rate
Specific Cytotoxic T Lymphocyte (CTL) response
Exploratory:
Biomarkers (PD-1, LAG3, TIM3, CTLA-4, etc.) related to the clinical outcome

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Histologically or cytologically confirmed hepatocellular carcinoma
2) Patients who are not eligible for curative surgical resection, or have not been eligible for regional therapy due to disease progression after surgery or locoregional treatment
3) Disease progression after at least one prior systemic regimen with Sorafenib, Lenvatinib or Atezolizumab plus Bevacizumab, or discontinuation of the regimen with Sorafenib or Lenvatinib due to intolerable toxicity
4) Patients who are able to undergo a biopsy as scheduled in the protocol to provide specimens
5) HLA-A*24:02, -A*02:01 or -A*02:06
6) Patients 20 years or older at the time of informed consent
7) ECOG PS 0-1
8) Child-Pugh class A liver score within 14 days prior to the first study treatment
9) Estimated life expectancy of >= 90 days
10) Adequate function of major organs, and the following laboratory parameters within 14 days prior to the first study treatment:
- Neutrophils >=1,500 /mm3
- Lymphocytes >=500 /mm3
- Platelet Count >=7.5x104 /mm3
- Hemoglobin >=8.0 g/dL
- Total Bilirubin <=ULNx3.0
- AST <=ULNx5.0
- ALT <=ULNx5.0
- Serum creatinine <=ULNx1.5, or Creatinine Clearance calculated by Cockcroft-Gault equation >=50 mL/min
- PT-INR <=1.7
- Serum Albumin >=2.8 g/dL
11) Recovery from previous treatment related toxicity (except for alopecia and controlled hypertension) to <= Grade 1
12) Measurable lesion according to RECIST v1.1
13) Ability to understand the study procedure and willingness to provide written consent

Exclude criteria

1)CNS metastases that are symptomatic or require treatment
2)Regorafenib, Ramucirumab or Cabozantinib treatment recommended
3)Malignancies other than HCC within the past 2 years except for carcinoma in situ or intramucosal carcinoma cured by regional therapy
4)Use of other anticancer drugs or other investigational products within 14 days prior to the first dose of study drug, or use of antibody drugs within 28 days prior to the first study treatment
5)Surgery within 28 days (as for puncture or drainage, within 14 days) prior to the first dose of study drug. Patients are not excluded unless recurrent abscess after puncture or drainage occur within 14 days prior to the first study treatment.
6)Following medical conditions:
-Uncontrolled heart diseases (e.g. NYHA Class III or IV of congestive heart failure, myocardial infarction within 1 year prior to the enrollment, unstable angina pectoris, arrhythmia requiring treatment)
-QTcF >470 msec or familial long-QT syndrome
-Uncontrolled diabetes or hypertension
-Active infection that requires systemic therapy such as antibacterial drugs and/or antiviral drugs.
Patients who have active infection of hepatitis B with HBV DNA <500 IU/mL within 28 days prior to the first study treatment, and have been undergoing anti-HBV treatment (e.g. nucleotide analogues) for at least 14 days prior to the first study treatment, are not excluded as long as they agree to stay on the same antiviral treatment throughout the study.
-Obvious interstitial lung disease or pulmonary fibrosis
-Severe mental disorder including dementia
-Effusion (pleural effusion, ascites or pericardial effusion) requiring puncture or drainage
-Esophageal varix or gastric varix requiring treatment
7)Known human immunodeficiency virus (HIV) positive status
8)Active state or history of recurrent or chronic autoimmune diseases.
Exceptions: Type I diabetes mellitus, hypothyroidism controlled by hormone replacement therapy, skin diseases (e.g. leukoderma, psoriasis, alopecia) without requiring systemic therapy, or autoimmune diseases whose recurrence will not be expected in the absence of extrinsic influences
9)Active state or history of hepatic encephalopathy
10)History of cerebrovascular disease, thrombosis or thromboembolism (pulmonary thromboembolism or deep vein thrombosis) within 180 days prior to the first study treatment
11)Radiation therapy within 28 days (palliative radiotherapy for pain-relieving within 14 days) prior to the first study treatment
12)Women who are pregnant or breastfeeding.
Women of breastfeeding, who agree not to breastfeed during and after the study, are not excluded. Women of childbearing potential who had negative results in pregnancy test (serum or urine) within 14 days prior to the first study treatment, are not excluded.
13)Patients who cannot agree to practice an effective contraception (e.g. condom, intrauterine device or oral contraception), from informed consent to 90 days after the last study treatment. As for women who use oral contraception, barrier contraception must be used concurrently.
Postmenopausal women (one year has passed after last menstruation) and men or women who have received surgical contraception, are not excluded.
14)History of organ transplantation or hematopoietic stem cell transplantation
15)Prior administration of HSP70 derived peptide, GPC3 derived peptide, hLAG-3Ig or Poly-ICLC
16)Known hypersensitivity reactions to any ingredients of CYT001
17)Unsuitable conditions for the study participation determined by investigators

Related Information

• Primary Sponsor: Kato Naoya