A Phase I Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of SON-DP in Subjects with Advanced Solid Tumors
* SON-DP is different from the conventional cancer cell-killing therapy which have high side effect, drug resistance, cancer recurrence and tumor heterogenicity, SON-DP is a novel transcription factor (TF) protein anticancer drug 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 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-A003-ST clinical trial, SON-DP is given to the participants with late stage solid tumors through 150-minutes IV infusion once a week at 4 dose levels during the first Phase I dose escalation to find the recommended phase II dose (RP2D) for the second Phase Ib does expansion stage that will focus on 2 cancer types including advanced primary liver cancer and advanced primary gastric cancer. * During Phase Ia dose escalation stage, an 3+3 design will be followed. 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 2 specific cancer types including advanced primary liver cancer and advanced primary gastric cancer. Two groups of cancer cohorts will be opened with eligible participants who have relapsed/refractory/intolerant to standard of care therapies of these two 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
96
Solution for IV administration
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
NOT_YET_RECRUITINGBeijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGNumber of participants with AEs, with abnormal vital signs, abnormal ECG readings, abnormal clinical laboratory tests results, abnormal physical examinations and abnormal ECOG performance status.
Time frame: Up to 7 months after the first dose
MTD (Maximum tolerable dose) / RP2D (Recommended dose for phase II)
Time frame: 28 days post first administration of SON-DP
ORR
Objective response rate (ORR)
Time frame: Up to 6 months after the first dose. Up to 9 months if treated for 9 cycles.
DCR
Disease control rate (DCR)
Time frame: Up to 6 months after the first dose
TTP
Time-to-event endpoints of time to disease progression (TTP)
Time frame: Up to 6 months after the first dose
DOR
Duration of response (DoR)
Time frame: Up to 6 months after the first dose
PFS
Progression-free survival (PFS)
Time frame: Up to 6 months after the first dose
OS
Overall Survival (OS)
Time frame: Up to 12 months after the first dose
Cmax
Maximum serum concentration (Cmax) of 3 proteins from SON-DP will be investigated.
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Beijing GoBroad Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe First Hospital of Lanzhou University
Lanzhou, Gansu, China
RECRUITINGSun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGSun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGJiangsu Province Hospital
Nanjing, Jiangsu, China
RECRUITINGThe First Affiliated Hospital of Xi 'an Jiaotong University
Xi'an, Shaanxi, China
RECRUITINGIntroduction to Cancer Hospital of Shandong First Medical University (Shandong Cancer Institute,Shandong Cancer Hospital)
Jinan, Shandong, China
RECRUITINGZhongShan Hospital Fudan University
Shanghai, Shanghai Municipality, China
RECRUITING...and 1 more locations
Time frame: Up to 6 months after the first dose
Tmax
Time to maximum serum concentration (Tmax) of 3 proteins from SON-DP will be investigated.
Time frame: Up to 6 months after the first dose
T1/2
Half-life (T1/2) of 3 proteins from SON-DP will be investigated.
Time frame: Up to 6 months after the first dose
AUC0-t
AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.
Time frame: Up to 6 months after the first dose
CL
Clearance (CL) in the serum of 3 proteins from SON-DP per unit of time will be investigated.
Time frame: Up to 6 months after the first dose