A First-in-Human Study of SON-DP in Participants With Relapsed/Refractory Intolerant to Standard of Care Therapies for Advanced/Metastatic Solid Tumors

Overview

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.

* 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.