None listed
Conditions
Brief summary
The aim of this study is to assess the safety and efficacy of a novel anti-cancer drug called SON-DP in patients with advanced or metastatic solid tumours that have relapsed or are not responding to standard treatment. This novel anti-cancer drug is different from the traditional cancer cell killing drug as it is expected to transform cancer cells into normal tissue cells via a SON-DP induced cancer cell reprogramming and re-differentiation process. Who is it for? You may be eligible to join this study if you are aged 18 years or older, and you have a histologically confirmed locally advanced or metastatic solid tumour that is relapsed or not responding to currently approved therapies. Study details All participants will be treated with SON-DP administered via a 90 minute intravenous infusion twice per week in 28-day cycles, for a maximum of 6 cycles. The first few participants enrolled will start at a low dose, and will be assessed for safety and anti-cancer activity of the drug. If determined to be safe, the next participants enrolled will receive a higher dose level, or alternatively will receive a lower dose level if side effects are experienced. For the duration of treatment and up to 1 month after completing treatment, participants will undergo blood tests and imaging to determine the safety and anti-cancer efficacy of SON-DP. Participants may also be asked to undergo tumour biopsies, although this will be voluntary for participants receiving lower dose levels. It is hoped that this study will show that this novel drug is safe and effective for the treatment of patients with advanced or metastatic solid tumours that have relapsed or are not responding to standard treatment. The information in this phase 1a study will be used to determine the optimal dose of SON-DP for future treatment of similar patients.
Interventions
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. In an effort to overcome the major challenges of the conventional cancer cell-killing therapy for high side effect, drug resistance, cancer recurrence, and tumour heterogenicity the sponsor is developing a protein anticanc
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. In an effort to overcome the major challenges of the conventional cancer cell-killing therapy for high side effect, drug resistance, cancer recurrence, and tumour heterogenicity the sponsor is developing a protein anticancer drug product, named SON-DP, previously referred to as REPROGRACON to treat the subjects with relapsed and advanced metastatic solid tumours. Cancer cell conversion is achieved by the SON-DP induced re-programming in situ inside tumour tissue into transient pluripotent stem cells (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). In addition, these in situ generated tiPSCs display a targeting effect that enables the generated tiPSCs to track down the distant metastatic cancer cells for OMPR. 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. This new cancer therapeutic strategy may provide an effective cancer therapy. SON-DP is proposed as an effective universal therapeutic drug for solid tumour cell-converting cancer therapy. The first-in-human (FIH) and first-in-class clinical study will be conducted in advanced cancer patients with solid tumours. The completed nonclinical studies, including pharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies, support the safety and efficacy of SON-DP protein drug product to be used in clinical studies of human participants. During dose escalation in Phase Ia, a total of 7 dose levels is proposed, from 0.2mg/kg to 6.0mg/kg. All seven dose level cohorts will follow a classic 3+3 escalation approach with the first two dose level cohorts being planned for an accelerated one participant only. An additional 8th cohort of up to 6 subjects may be enrolled at the discretion of the SMC, in order to evaluate an intermediary dose level and/or to further evaluate the MTD/RP2D. Participants will receive SON-DP through intravenous infusion (IV) at the assigned dose level in 28-day cycles, two times a week for the maximum of 6 cycles. In general, SON-DP administration will be continued in 28-day cycles until complete response or disease progression, participant intolerance, or participant withdrawal or completion of study treatment period. For the dose level 1 or 2, single eligible participants will be enrolled and treated. If one of these participants experience a drug related Grade 2 (Grade 2 or higher) adverse event (AE) during the DLT observation period regardless of attribution, the current cohort and all subsequent cohorts will be expanded to a minimum of 3 participants and will follow the 3+3 dose limiting toxicity (DLT) evaluation rule. For the dose level 3 and beyond, eligible participants will be enrolled in cohorts of 3, at each dose, according to the 3+3 design. Each escalation decision to next higher dose will be made by the Safety Monitoring Committee (SMC). The RP2D will be determined using Cycle 1 information as well as available subsequent SON-DP treatment information. For participants receiving dose levels from 2mg/kg up to 6mg/kg, tumour biopsies will be mandatory at screening and at Cycle 2 week 1 respectively. For subjects receiving the lower dose levels, tumour biopsies are optional or voluntary. Biopsies will take up to 1 or 2 hours (depending on the biopsy method, such as CT-guided) for the biopsy procedure excluding the observation period after the biopsy and will be performed by the participants surgical oncologist or contracted surgical oncologist. The Site Principal Investigator will assess the situation for ease of biopsy and safety of the participant, only one biopsy will be performed. Archived tumour tissue will also be collected. The study staff who administer the SON-DP must have the required qualifications and have completed all necessary study specific training for SON-DP treatment and intravenous infusion.
Sponsors
Qurgen Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase 1a: 1. Participants are required to have: a. Histological confirmed locally advanced or metastatic solid tumour, that is relapsed, refractory, or intolerant to currently approved therapies. b. Measurable or evaluable disease by RECIST v1.1. 2. Willing and be able to understand and to sign an informed consent form (ICF) and to comply with all aspects of the protocol. 3. Female or male participants aged greater than or equal to 18 years. 4. Participants who use tobacco products can be included only if they agree that the use of nicotine- containing products (including nicotine patches) will not be permitted while they are in the study centre. 5. The ECOG performance status less than or equal to 1. 6. Life expectancy greater than 3 months in the Investigator’s opinion. 7. Participants must be candidates for and agree to the placement of a central venous access line and further must be able, in the opinion of the Investigator, to manage care of this line. 8. Participants with treated brain metastases are allowed but should be neurologically stable (for 4 weeks post-treatment as assessed by central nervous system (CNS) imaging and prior to study enrolment) and off steroids for at least 2 weeks before administration of any study treatment. 9. Adequate hepatic/renal function 10. Adequate haematological function 11. Coagulation tests within an acceptable range
Exclusion criteria
1. Participation in an interventional, investigational study within 2 weeks or 5 half-lives, whichever is shorter of the first dose of study treatment. 2. Presence of overt leptomeningeal or active CNS metastases or primary tumour or CNS metastases that require local CNS-directed therapy (e.g., radiotherapy or surgery) or increasing doses of corticosteroids within the prior 2 weeks. 3. Impaired cardiac function or clinically significant cardiac disease, including any of the following: a. Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association [NYHA] Grade greater or equal to 2), left ventricular ejection fraction (LVEF) less than 50% as determined by multiple gated acquisition (MUGA) or echocardiogram (ECHO), recorded in medical history of last two years or clinically significant arrhythmia. b. QT interval corrected for heart rate using Fridericia’s formula (QTcF) greater than 470 ms ECG or congenital long QT syndrome at the Screening Visit. c. Acute myocardial infarction or unstable angina pectoris less than 6 months prior to the first dose of study drug. 4. Uncontrolled hypertension (systolic blood pressure greater than 150 mmHg and diastolic blood pressure greater than 100 mmHg), or in the opinion of the Investigator: a recent history of hypertension crisis, or a recent history of hypertensive encephalopathy. 5. History of stroke or clinically significant intracranial haemorrhage within 6 months before first dose of study drug. 6. Participants with active human immunodeficiency virus (HIV) infection or if subject has a history of HIV, subject must be confirmed to not have active infection. 7. Participants who have active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. 8. Chronic liver disease or chronic hepatitis (Child-Pugh Class B or C hepatic impairment). 9. Prior or current malignant disease other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; adequately treated cervical carcinoma-in-situ completely resected basal cell or squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
Outcome results
None listed