Trial Title:
Phase I Study to Evaluate Safety and Anti-tumor Activity of PB101, an Anti-angiogenic Immunomodulating Agent
NCT ID:
NCT06075849
Condition:
Solid Tumor, Adult
Solid Tumor
Gastric Cancer
Hepatocellular Carcinoma
Metastatic Colorectal Cancer
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Neoplasms
Angiogenesis Inhibitors
Antineoplastic Agents
Angiogenesis Modulating Agents
Immuno Modulating Agents
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PB101
Description:
Cohorts of 3-6 patients receive PB101 until the MTD is determined. The dose (2 mg/kg-15
mg/kg) assigned to the cohort will be administered weekly for two 28-day cycles or until
progressive disease (PD), unacceptable toxicity, withdrawal of subject consent, and/or
the investigator's decision to discontinue the study treatment occurs.
Administration may be continued for subjects in whom PB101 provides clinical benefits at
the discretion of the investigator.
Arm group label:
PB101
Summary:
This clinical trial is designed as a multi-center, open-label, dose-escalation,
dose-expansion, phase 1 clinical trial and will be evaluating the safety and efficacy of
PB101 in patients with advanced solid tumors who have progressed after standard of care.
PB101 may stop the growth of tumor cells by blocking blood flow to the tumor and
modulating the tumor microenvironment.
Detailed description:
Primary Objectives
To assess the safety and tolerability of PB101 and determine the maximum tolerated dose
(MTD) and/or the recommended phase-2 dose
Secondary Objectives
1. To characterize the pharmacokinetics of PB101.
2. To identify the preliminary anti-tumor activity of PB101.
3. To assess the immunogenicity of PB101.
Tertiary Objectives
To explore the correlation between potential pharmacodynamic (PD) biomarkers (e.g.,
vascular endothelial growth factor(VEGF)-A, placental growth factor (PlGF) and VEGFR1
signaling) and anti-cancer activity of PB101.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria.
1. ≥19 years of age
2. Patients with unresectable locally advanced or metastatic solid tumor, confirmed
histologically and cytologically, who is refractory to existing standard of care or
has progressive disease and has no other available standard of care available.
3. Patient who has at least one measurable or non-measurable but evaluable lesion that
meets the RECIST version 1.1.
4. Patient whose expected survival period is 12 weeks or longer.
5. Patient with eastern cooperative oncology group (ECOG) performance status ≤ 2
6. Patient whose adequate hematological function, and kidney and liver functions have
been confirmed by the following criteria. (Laboratory tests are allowed to
re-conducted within the screening period.)
7. Patient with adequate anticoagulant functions according to the following criteria:
- Without receiving anticoagulant therapy, patient whose international normalized
ratio (INR) is ≤ 1.5 x upper limit of normal (ULN) and partial thromboplastin
time (PTT) is ≤ 5 seconds above the ULN.
- When receiving an oral anticoagulant or low molecular weight heparin, patient
whose prothrombin time (PT) or PTT is confirmed to be stable for at least 2
weeks.
- When receiving warfarin, patient whose INR is ≤3.0 There must be no active
bleeding (bleeding within 14 days) or pathological conditions with a high risk
of bleeding (e.g., tumor with macrovesicular invasion or known varicose vein).
8. Patient who voluntarily gave informed consent in writing to participate in this
clinical trial after being provided with information on the nature and risks of the
study as well as the expected desirable benefits and AEs of the investigative
product (IP).
Exclusion Criteria:
Patients who meet any of the following criteria cannot participate in this clinical
trial.
1. Patient expected to show hypersensitivity to the active ingredient and components of
PB101 or similar drugs.
2. Patient with the following medical history (including surgery/procedure history)
confirmed.
- Major surgery within 4 weeks prior to administration of the IP, and clinically
significant traumatism.
- Cardiovascular disease (including unstable angina, myocardial infarction,
stroke, and transient ischemic attack), congestive heart failure (NYHA class
III or IV), or clinically significant arrhythmia uncontrollable by medication
within 24 weeks prior to administration of the IP.
- Patient whose left ventricular ejection fraction (LVEF) measured by
echocardiography, multigated blood pool scan (MUGA) scan or the standard
procedure at the institution before administration of the IP is less than the
lower limit of normal at the institution. However, if there is no reference
LVEF set at the institution, 50% will be treated as the reference level.
- Vascular disorders (e.g., deep vein thrombosis, pulmonary embolism, aortic
aneurysm, and peripheral arterial thrombosis) within 24 weeks prior to
administration of the IP
- Life-threatening (Grade 4) venous thromboembolism (regardless of the duration,
even if it is a past medical history)
- Medical history of primary malignancies other than indication for this clinical
trial. However, the following cases are allowed:
- Not less than 3 years have passed since the cure diagnosis of a primary
malignancy. However, in case of papillary thyroid cancer, patients who
underwent curative resection can participate in the study regardless of
the duration.
- At least 1 year has passed since complete resection of cutaneous basal
cell carcinoma/squamous cell carcinoma of the skin or successful treatment
of cervical carcinoma in situ.
- Psychiatric disorder that may significantly affect the participation in the
study at the discretion of the investigator.
3. Patient with the following comorbidities confirmed at the time of participation in
the study.
- Squamous cell carcinoma of the lung (current and past medical history).
- Interstitial lung disease or pulmonary fibrosis (current and past medical
history).
- The following hemorrhage-related and digestive system diseases (current and
past medical history).
- Evidence of active bleeding, hemorrhagic diathesis, coagulopathy, and
tumor with macrovesicular invasion.
- Clinically significant medical history of digestive system, such as peptic
ulcer, gastrointestinal bleeding, gastrointestinal or non-gastrointestinal
fistulas or perforations, intra-abdominal abscesses, clinical symptoms and
signs of gastrointestinal obstruction, and inflammatory bowel disease.
- Clinically significant pericardial effusion, pleural fluid, or ascites.
However, in case of ascites, patients who do not require paracentesis for
improvement of the symptoms can participate in the study.
- Uncontrolled hypertension (systolic blood pressure (SBP) > 150 or diastolic
blood pressure (DBP) > 90 mmHg even after medication).
- Infection of active hepatitis B* or C† virus
*Hepatitis B surface antigen (HBsAg)-positive at screening. However, for HBsAg
positive, not excluded if the patient is taking antiviral agents stably.
†Hepatitis C virus antibody (HCV Ab)-positive at screening. However, if the
result of HCV RNA test is negative, participation is possible.
- Human immunodeficiency virus (HIV)-positive.
- Severe infection or other uncontrolled active infection that requires
administration of systemic antibiotics, antivirals, etc. at the discretion of
the investigator
- New or active brain metastases. However, patients who do not need central
nervous system (CNS) treatment immediately (or within 1 cycle) at the
discretion of the investigator can participate in the study.
- Leptomeningeal metastasis
- Serious and unhealed wound or fracture
4. Patient who received the following treatment regimens (drug/non-drug)
- patient who received the following anti-cancer treatments other than this IP.
- Chemotherapy, hormone therapy, and radiation therapy within 2 weeks prior
to administration of the IP. However, patients who completed local
radiotherapy as a palliative therapy for the purpose of pain relief in
areas other than the target lesion (e.g., site of bone metastases) and
recovered from following acute toxicity (e.g., myelosuppression).However,
patients who completed local radiotherapy as a palliative therapy for the
purpose of pain relief in areas other than the target lesion (e.g., site
of bone metastases) and recovered from following acute toxicity (e.g.,
myelosuppression).However, patients who completed local radiotherapy as a
palliative therapy for the purpose of pain relief in areas other than the
target lesion (e.g., site of bone metastases) and recovered from following
acute toxicity (e.g., myelosuppression).
- Targeted therapies or immunotherapy within 4 weeks prior to administration
of the IP.
- Administration history of nitrosoureas or mitomycin-C within 6 weeks prior
to administration of the IP.
- Administration history of nonsteroidal anti-inflammatory drugs (NSAID) and
anti-platelet agents within 7 days prior to administration of the IP. However,
for aspirin, doses of 325 mg/day are allowed.
5. Patient who participated in another clinical study within 4 weeks prior to
administration of the IP and received (underwent procedure of) an investigational
drug (or medical device).
6. Patient who continues to experience a clinically significant toxicity or adverse
event of Grade 2 or higher (based on NCI-CTCAE v5.0) after prior anti-cancer
therapy. However, hair loss (any grade) and neuropathy (Grade 2 or lower) are
exceptions.
7. Pregnancy test positive at screening, or pregnant or lactating woman.
8. Female or male subject of childbearing potential who does not agree to stay
abstinent or use an effective method of contraception† during the study period and
for at least 26 weeks (women) or 14 weeks (men) after the last dose of the IP.
†Effective method of contraception:
- Hormonal contraceptive: Subdermal implants, injections, oral contraceptives,
etc. However, in case of ovarian/breast cancer, hormonal contraception is not
allowed.
- Implantation of an intrauterine device or intrauterine system: Loop, and
hormone-containing intrauterine system.
- Sterilization procedure or surgery of the subject or his/her spouse (partner):
Vasectomy, tubal ligation, etc.
9. Other patients deemed ineligible to participate in the study by the investigator.
Gender:
All
Minimum age:
19 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHA University Bundang Medical Center
Address:
City:
Seongnam
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Hong Jae Chon, MD/PhD
Phone:
+82)31-780-5000
Email:
hongjaechon@gmail.com
Facility:
Name:
Seoul National University Bundang Hospital
Address:
City:
Seongnam
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Keun Wook Lee, MD/PhD
Phone:
+82)2-1588-3369
Email:
imdoctor@snu.ac.kr
Facility:
Name:
The Catholic University of Korea Seoul St. Mary's Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Not yet recruiting
Contact:
Last name:
Myoung-An Lee, MD/PhD
Phone:
+82)2-1588-1511
Email:
angelamd@catholic.ac.kr
Start date:
October 25, 2023
Completion date:
January 2025
Lead sponsor:
Agency:
Panolos Bioscience
Agency class:
Industry
Source:
Panolos Bioscience
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06075849
https://www.panolos.com
https://www.youtube.com/watch?v=HPGW7sunrsI
