Phase I Study to Evaluate Safety and Anti-tumor Activity of PB101, an Anti-angiogenic Immunomodulating Agent

NCT06075849 | Recruiting Phase 1

• 1 other identifier: PB101_101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Solid Tumor, Adult; Solid Tumor; Gastric Cancer; Hepatocellular Carcinoma; Metastatic Colorectal Cancer; Advanced Solid Tumor

Keywords

Neoplasms; Angiogenesis Inhibitors; Antineoplastic Agents; Angiogenesis Modulating Agents; Immuno Modulating Agents

Outcome Measures

Primary Outcomes (5)

• Dose limiting toxicity (DLT)

  Frequency by dose group

  8 weeks

• Permanent discontinuation / dose reduction due to adverse events (AE)

  Frequency and percentage by dose group due to adverse drug reactions (ADR)

  8 weeks

• Adverse events

  Incidence by dose group for treatment-emergent adverse events (TEAEs), ADRs, serious adverse events (SAEs), and serious ADRs

  8 weeks

• Electrocardiogram (ECG)

  Clinically significant changes in ECG results compared to baseline

  8 weeks

• Left ventricular ejection fraction (LVEF)

  Multigated blood pool scan (MUGA) or echocardiography (ECHO), clinical significance and significant changes evaluated

  8 weeks

Secondary Outcomes (7)

• Objective response rate (ORR)

  8 weeks

• Duration of response (DOR)

  8 weeks

• Progression free survival (PFS)

  8 weeks

• Disease control rate (DCR)

  8 weeks

• Time to progression (TTP)

  8 weeks

Other Outcomes (7)

• Area under the concentration-time curve (AUC)

  8 weeks

• Maximum plasma concentration (Cmax)

  8 weeks

• Minimum plasma concentration (Cmin)

  8 weeks

Study Arms (1)

PB101

EXPERIMENTAL

A total of 6 cohorts are planned, and each dose escalation will proceed in a traditional 3+3 scheme.

Drug: PB101

Interventions

PB101 DRUG

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.

PB101

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥19 years of age
• 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.
• Patient who has at least one measurable or non-measurable but evaluable lesion that meets the RECIST version 1.1.
• Patient whose expected survival period is 12 weeks or longer.
• Patient with eastern cooperative oncology group (ECOG) performance status ≤ 2
• 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.)
• 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).
• 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).

You may not qualify if:

• Patients who meet any of the following criteria cannot participate in this clinical trial.
• Patient expected to show hypersensitivity to the active ingredient and components of PB101 or similar drugs.
• 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.
• 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).

Sponsors & Collaborators

• Panolos Bioscience: lead

Study Sites (3)

CHA University Bundang Medical Center

Seongnam, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam, South Korea

RECRUITING

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, South Korea

NOT YET RECRUITING

Related Publications (2)

• Lee JE, Kim C, Yang H, Park I, Oh N, Hua S, Jeong H, An HJ, Kim SC, Lee GM, Koh GY, Kim HM. Novel glycosylated VEGF decoy receptor fusion protein, VEGF-Grab, efficiently suppresses tumor angiogenesis and progression. Mol Cancer Ther. 2015 Feb;14(2):470-9. doi: 10.1158/1535-7163.MCT-14-0968-T. Epub 2014 Dec 22.

  PMID: 25534360 BACKGROUND

• Go EJ, Yang H, Lee SJ, Yang HG, Shin JA, Lee WS, Lim HS, Chon HJ, Kim C. PB101, a VEGF- and PlGF-targeting decoy protein, enhances antitumor immunity and suppresses tumor progression and metastasis. Oncoimmunology. 2023 Sep 20;12(1):2259212. doi: 10.1080/2162402X.2023.2259212. eCollection 2023.

  PMID: 37744990 BACKGROUND

Related Links

• Company link
• Mechanism of Action

MeSH Terms

Conditions

Stomach Neoplasms; Carcinoma, Hepatocellular; Colorectal Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Hong Jae Chon, MD/PhD

  CHA University Bundang Medical Center

  PRINCIPAL INVESTIGATOR

• Keun Wook Lee, MD/PhD

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

• Myung-Ah Lee, MD/PhD

  The Catholic University of Korea

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin A Shin, PhD

CONTACT

+82)31-8055-0886; jashin@panolos.com

Study Design

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

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 10, 2023
• Study Start: October 25, 2023
• Primary Completion: October 1, 2024
• Study Completion: January 1, 2025
• Last Updated: February 23, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3)