Trial Title:
A First-in-Human Study of SON-DP in Participants With Relapsed/Refractory Intolerant to Standard of Care Therapies for Advanced/Metastatic Solid Tumors
NCT ID:
NCT05989724
Condition:
Solid Tumor
Breast Cancer
Pancreatic Cancer
Ovarian Cancer
Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Pancreatic Neoplasms
Ovarian Neoplasms
Conditions: Keywords:
SON-DP
Solid Tumor
Breast Cancer
Pancreatic Cancer
Ovarian Cancer
Colorectal cancer
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
This is a first-in-human and first-in-class, open-label, Phase I clinical trial including
a Phase Ia dose escalation stage for the participants with all solid tumor types using
seven dose levels of SON-DP to determine the RP2D, MTD and DLT; and a Phase Ib dose
expansion stage for the participants of four arms including breast cancer, pancreatic
cancer, ovary cancer or colorectal cancer using the RP2D of SON-DP obtained from Phase
Ia.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SON-DP
Description:
Solution for IV administration
Arm group label:
Dose escalation, Cohort 1
Arm group label:
Dose escalation, Cohort 10
Arm group label:
Dose escalation, Cohort 11
Arm group label:
Dose escalation, Cohort 2
Arm group label:
Dose escalation, Cohort 3
Arm group label:
Dose escalation, Cohort 4
Arm group label:
Dose escalation, Cohort 5
Arm group label:
Dose escalation, Cohort 6
Arm group label:
Dose escalation, Cohort 7
Arm group label:
Dose escalation, Cohort 8
Arm group label:
Dose escalation, Cohort 9
Arm group label:
Dose expansion, Arm 1
Arm group label:
Dose expansion, Arm 2
Arm group label:
Dose expansion, Arm 3
Arm group label:
Dose expansion, Arm 4
Summary:
This proposed Phase I clinical trial of SON-DP is an FIH, open-label, Phase Ia/Ib dose
escalation and expansion study to evaluate the safety, tolerability, PK, and PD of SON-DP
in participants with relapsed/refractory/intolerant to standard of care therapies, for
advanced/ metastatic solid tumors.
Detailed description:
- In an effort to overcome the major challenges of the conventional cancer
cell-killing therapy for high side effect, drug resistance, cancer recurrence and
tumor heterogenicity, Qurgen Inc. is developing a novel transcription factor (TF)
protein anticancer drug, named SON-DP, to treat the Participants with relapsed and
advanced metastatic solid tumors. Proposed as an effective therapeutic drug product
for a cell-converting cancer therapy, SON-DP is expected to transform cancer cells
in situ into normal tissue cells via a SON-DP induced cancer cell reprogramming and
re-differentiation process as an innovative rationale.
- SON-DP is developed based on the rationale of cancer cell conversion into normal
tissue cells as the primary mechanism of actions of a new cancer therapy, not by
cancer cell-killing, the traditional goals of chemotherapy, radiation therapy,
targeted therapy and immune therapy. Cancer cell conversion is achieved by the
SON-DP induced pluripotent re-programming in situ inside tumor tissue into transient
iPSCs (tiPSCs) that quickly re-differentiate into normal tissue cells induced by the
differentiating resident tissue environment. The in situ generated tiPSCs either
secrete exosomes, providing the embryonic stem cells (ESC)-like microenvironments to
transform the surrounding cancer cells into normal tissue cells for an overall
malignant phenotype reversion (OMPR) (an effect named as a bystander effect), or
display a targeting effect that enables the in situ generated tiPSCs to track down
the distant metastatic cancer cells for OMPR (an effect named as a tropism effect).
The SON-DP-induced cell reprogramming also restored the mutation-caused and
compromised p53 checkpoint in cancer cells to re-establish cell quality control
system that ensures the downstream re-differentiation of the in situ generated
tiPSCs into normal tissue cells. Overall, this SON-DP-induced re-programming and
re-differentiation process is capable of transforming both primary and metastatic
cancer cells into normal tissue cells.
- Preclinical studies demonstrated that treatment of tumors with SON-DP resulted in
eradication of late-stage cancers and long term (over 3 years) survival without
teratoma formation and cancer recurrence in multiple tumor-bearing mouse/rat
(syngeneic) or human xenograft rodent models, providing high treatment efficacy of
this cell-converting cancer therapy. Thus, the cell-converting cancer therapy
rationale represents a new cancer therapeutic strategy. SON-DP was tolerated in
tumor-bearing rodents, as well as in naïve rats, dogs, and monkeys as demonstrated
by GLP-enabled (rats and dogs) and non-GLP (monkey) toxicity study and after
repeated IV administrations at higher doses compared with the planned clinical dose
range. Therefore, the current nonclinical studies, including pharmacodynamics (PD),
pharmacokinetics (PK) and toxicology studies, support the safety and efficacy of
SON-DP TF protein drug product to be used in clinical studies of human participants.
This first-in-human (FIH) clinical study will be conducted in selected types of
relapsed/refractory advanced/metastatic solid tumors as a step in demonstrating the
utility of this anticancer agent.
- In this SON-DP-A001-ST clinical trial, SON-DP is given to the participants with late
stage solid tumors through 90-minutes IV infusion either once a week or twice a week
at first 4 dose levels during the first Phase I dose escalation stage with the
purpose to identify the final schedule (either once a week or twice a week) for the
last 3 higher dose levels and the recommended phase II dose (RP2D) for the second
Phase Ib does expansion stage that will focus on 4 cancer types including breast
cancer, pancreatic cancer, ovarian cancer and colorectal cancer.
- During Phase Ia dose escalation stage, an accelerated 3+3 design will be followed. A
Safety Monitoring Committee (SMC) will be formed to evaluate all the safety,
efficacy, pharmacokinetic and pharmacodynamic data of each dose level cohort to
decide if the SON-DP dose level should be either escalated to the next dose level or
de-escalated to one level below or determination of maximum tolerated dose (MTD) or
RP2D confirmation or others. Phase Ia will enroll the participants with various
types of solid tumors that metastasized and not response to standard treatment.
- During Phase Ib dose expansion stage, SON-DP will be used, at RP2D dose level, to
treat the participants with 4 specific cancer types including breast cancer,
pancreatic cancer, ovary cancer or colorectal cancer. Four groups of cancer cohorts
will be opened with eligible participants who have relapsed/refractory/intolerant to
standard of care therapies of these four advanced/metastatic solid tumors.
Participants will be followed for safety, confirmation of the RP2D, PK, PD, and
anti-tumor activity as measured by standard assessment tools.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed written informed consent;
2. Male or female participants aged ≥ 18 years;
3. For Phase Ia: Participants with histologic diagnosis and confirmed solid tumor; For
Phase Ib: Participants with one of the four tumor types: breast cancer, pancreatic
cancer, ovarian cancer or colorectal cancer;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study
entry and an estimated life expectancy of at least 3 months;
5. Agree to the placement of drug infusion venous access;
6. For high dose group, agree for two biopsies, one at screening and one at 1st week of
cycle 3;
7. Adequate hematological function;
8. Adequate hepatic/renal function;
9. Acceptable coagulation function;
10. Recovered from prior treatment Adverse Effect;
11. Effective contraception for female participant with child bearing potential
participants and sexually active male participants.
Exclusion Criteria:
1. Participation in investigational study within 2 weeks or 5 half-lives, whichever is
shorter of the first dose of study treatment.
2. Impaired cardiac function or clinically significant cardiac disease.
3. History of stroke or clinically significant intracranial hemorrhage within 6 months
before first dose of study drug.
4. Malignant disease, other than that being treated in this study.
5. Anticancer therapy within 5 half-lives or 2 weeks (whichever is shorter) prior to
study entry.
6. Active infection requiring intravenous systemic antibiotic or antiviral therapy
within 14 days prior to the first dose of study drug.
7. Major surgery within 4 weeks of the first dose of study treatment.
8. Any medical condition that would, in the Investigator's judgment, prevent the
participant's participation in the clinical study due to safety concerns, compliance
with clinical study procedures, or interpretation of study results.
9. Active pneumonitis, the suspected pneumonitis that cannot be ruled out based on the
imaging at Screening or based on the Investigator's judgement and a history of the
(non-infectious) pneumonitis that required steroids within the past 12 months
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Banner MD Anderson Cancer Center (BMDACC)
Address:
City:
Gilbert
Zip:
85234
Country:
United States
Status:
Recruiting
Contact:
Last name:
Katt Mackin
Phone:
480-256-3425
Email:
Katt.Mackin@bannerhealth.com
Investigator:
Last name:
Jason Niu
Email:
Principal Investigator
Facility:
Name:
Henry Ford Health System
Address:
City:
Detroit
Zip:
48202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Cesar Figueras
Phone:
313-433-8915
Email:
cfiguer1@hfhs.org
Investigator:
Last name:
Amy Weise
Email:
Principal Investigator
Facility:
Name:
Carolina BioOncology Institute
Address:
City:
Huntersville
Zip:
28078
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ashley McClain Wallace
Phone:
980-441-1021
Email:
awallace@carolinabiooncology.org
Investigator:
Last name:
John Powderly
Email:
Principal Investigator
Facility:
Name:
Stephenson Cancer Center, University of Oklahoma
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christina Caldwell
Phone:
405-271-8001
Phone ext:
48171
Email:
Christina-Caldwell@ouhsc.edu
Investigator:
Last name:
Susanna Ulahannan
Email:
Principal Investigator
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Siqing Fu
Phone:
877-632-6789
Email:
siqingfu@mdanderson.org
Contact backup:
Last name:
Jing Peng
Phone:
713-792-2208
Email:
jingpeng@mdanderson.org
Investigator:
Last name:
Siqing Fu
Email:
Principal Investigator
Start date:
September 19, 2023
Completion date:
March 2026
Lead sponsor:
Agency:
Qurgen Inc.
Agency class:
Industry
Source:
Qurgen Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05989724
