Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000202662
Ethics application status
Approved
Date submitted
21/12/2022
Date registered
24/02/2023
Date last updated
29/02/2024
Date data sharing statement initially provided
24/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A First-in-Human, Open-label, Phase Ia Dose Escalation Study of SON-DP in subjects with advanced/metastatic solid tumors that have relapsed or are refractory/intolerant to standard of care therapies
Scientific title
A First-in-Human (FIH), Open-Label, Phase Ia Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SON-DP in Subjects with Advanced/Metastatic Solid Tumours that have relapsed or are refractory/intolerant to standard of care therapies
Secondary ID [1] 308398 0
SON-DP-A002-ST
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid tumor malignancies 328557 0
Condition category
Condition code
Cancer 325573 325573 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 325110 0
Treatment: Drugs
Comparator / control treatment
NA
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333415 0
To assess the safety and tolerability of SON-DP in participants with advanced/metastatic solid tumours that have relapsed or are refractory/intolerant to standard of care therapies. The parameters assessed for safety endpoints include:
- Adverse events - Incidence, severity and relationship of Adverse Events/Serious Adverse Events (including withdrawals due to AEs). AEs and SAEs will be assessed for severity and causality (relationship of the event to the investigational product) by the study investigator using the specified grading definitions Common Terminology Criteria for Adverse Events.
- Vital signs- Change from baseline in vital signs (systolic and diastolic blood pressure, respiration rate, body temperature and pulse rate). Blood pressure will be measured using sphygmomanometer, body temperature will be measured using a thermometer, Heart rate (HR) is measured using vital sign machine and respiratory rate is measured manually via 60-second count.
- ECG- Change from baseline in electrocardiogram (ECG) parameters
- Clinical laboratory tests - (Blood and Urine samples) Change from baseline in clinical laboratory parameters (haematology, serum chemistry, coagulation and urinalysis).
- Physical examination - A directed physical examination will include, at a minimum, assessments of the skin, lungs, cardiovascular system, palpable tumour, and abdomen (liver and spleen).
- ECOG Performance- will be assessed by the status up to last safety follow up visit and baseline medical conditions.
- Tolerability assessed by summarising the number of dose delays and dose reductions/interruptions recorded in the participant's electronic case report form (eCRF). Reasons for dose delays and dose reductions/interruptions will be listed by participant and summarized. Assessment will include review of dose interruptions, reductions, and doses administered up to the last safety Follow-up Visit.
Timepoint [1] 333415 0
The timepoints include:
- Adverse events (AEs) - AEs assessment will be performed throughout the study period from Screening through to 30 Days after last infusion of study drug (Follow Up/End of Treatment (EOT) Visit). Participants who discontinue SON-DP will have an EOT Visit (within 30 days from the last infusion or on the day/visit of the decision to discontinue treatment). Participants who stop SON-DP but who have not experienced disease progression and do not start new alternative therapy will continue study visits and assessments until disease progression or decision to discontinue from study participation.
- Vital Signs - Vital Signs are performed during Screening, Week 1 - Day 1 pre-infusion, every 30 mins during infusion, post EOI, 1 hr, 2 hrs post-End of infusion (EOI) & Day 4 pre-infusion, every 30 mins during infusion, on completion of dosing, 1 hr post-dose. Week 2- Day 8 and Day 11 pre-dose, every 30 mins during dosing, post-EOI, 1 hr post-EOI. Week 3 - Day 15 and 18 pre-infusion, every 30 mins during infusion, post-EOI, 1 hr post-EOI. Week 4- Day 22 and Day 25 pre-infusion, every 30 mins during infusion, post-EOI, 1 hr post-EOI. Cycle 2- Week 1- Day 1 pre-infusion, every 30 mins during infusion, post-EOI, 1 hr, 2 hrs post-EOI and Day 4 pre-infusion, every 30 mins during infusion, post-EOI, 1 hr post-EOI. Week 2 - Day 8 and 11 pre-infusion, every 30 mins during infusion, post-EOI, 1 hr post-EOI. Week 3 - Day 15 and 18 pre-infusion, every 30 mins during infusion, post-EOI, 1 hr post-EOI, Week 4 - Day 22 and 25 pre-infusion, every 30 mins during infusion, post-EOI, 1 hr post-EOI and on Follow up visit 30 Days after last infusion.
- ECG- ECGs will be obtained at Screening, pre-infusion on Day 1 of Cycles 1-4, EOT, and as clinically indicated. Whenever ECG and PK samples are specified to be collected at the same time, ECG will be obtained before the PK sampling.
- Laboratory tests- Haematology and chemistry tests will be performed pre-infusion at Screening, Days 1, 4, 8, and 18 of Cycle 1, Day 1 of each subsequent cycle, and at the EOT visit. During Cycle 1, assessments should be performed within 24 hours prior to infusion. If the screening assessment was obtained within 1 week prior to the first infusion of Cycle 1 and the participant is clinically stable, it is not necessary to repeat the assessment at Cycle 1, Day1. Urinalysis should be obtained pre-infusion at Screening, Days 1, 4, 8, and 18 of Cycle 1, Day 1 of each subsequent cycle, and at the EOT. INR or PT and PTT will be obtained pre-infusion at Screening, Days 1, 4, 8, and 18 of Cycle 1, Day 1 of each subsequent cycle, and at the EOT visit.
- Physical examination- A complete physical examination at screening and End of Treatment, including height, will include the following systems: skin, head, eyes, ears, nose, throat, respiratory system, cardiovascular system, GI system, neurological condition, blood and lymphatic systems, and the musculoskeletal system . Symptom-directed physical examination will be conducted on Day 1 of Cycle 1 before the first infusion of study treatment and at subsequent safety assessment visits. Directed physical examination will include, at a minimum, assessments of the skin, lungs, cardiovascular system, palpable tumour, and abdomen (liver and spleen).
- ECOG Performance- During Cycle 1, ECOG Scale of Performance Status (PS) will be assessed on the day of drug administration, at EOT and as clinically indicated. During subsequent cycles, ECOG PS will be assessed on Day 1 of the cycle.
- Tolerability assessment - Tolerability assessment will include review of dose interruptions, reductions, and doses administered up to the last safety Follow-up Visit 30 Days after last dose.
Primary outcome [2] 333416 0
To assess dose-limiting toxicity (DLT) which is defined as any Grade 3 or higher adverse event (AE) that may be related to SON-DP.
The DLT evaluation period is the Cycle 1 treatment period based on the 3+3 evaluation rule:
• If there are no DLTs in the first 3 participants in Cycle 1, dose escalation to the next higher dose level may proceed.
• If 1 of the 3 participants experiences a DLT, that dose level will be expanded to 6 participants (3 additional participants will be enrolled).
• If 2 participants at a given dose level experience a DLT, further accrual to the cohort will be terminated.

The next lower dose level will be expanded to 6 participants or if 6 participants have already been enrolled and no more than 1 of the 6 experiences a DLT, then this lower dose level will be considered the MTD. This process may be repeated if the DLT rate exceeds 33%.

Adverse events that occur after Cycle 1 will be considered when determining whether the dose should be escalated.
Timepoint [2] 333416 0
- Eligible participants will be treated according to the assigned dose level of SON-DP until the MTD is established. Dose escalation may be stopped if the SMC determines that a satisfactory PD signal has been observed in addition to the DLT finding.

The above is determined by the data received from cycle 1. The time points used to assess the following are the same as primary timepoint 1.
Primary outcome [3] 333674 0
To assess the maximum tolerated dose (MTD). MTD is the dose level at which 2 participants out of 3 in a cohort experience a DLT.
The MTD will be determined by the safety monitoring committee (SMC) after evaluation of all safety data as well as, available PK, PD/biomarker and anti-tumour activity data during dose escalation.
Timepoint [3] 333674 0
The timepoints include:
- After each dose escalation cohort has completed its Cycle 1 observation period, the SMC will review and assess all available safety data obtained from the cohort along with available PK data to determine the MTD.
Secondary outcome [1] 416990 0
To assess the anti-tumour activity of SON-DP.
This will be assessed by the following:
Evaluation of tumour response based on the RECIST v1.1 evaluation of imaging assessments (CT or MRI). All measurable lesions should be assessed and documented at the Screening Visit and throughout the study for each participant.
Timepoint [1] 416990 0
Imaging assessments - CT or MRI scans conducted at Screening and every 8 weeks for 24 weeks. In the absence of disease progression, tumour assessments should continue regardless whether participants discontinue study treatment, unless the participant starts new anti-cancer treatment, dies, withdraws consent, or the study is terminated by the Sponsor, whichever occurs first.
Secondary outcome [2] 416991 0
To characterize the plasma PK profile of the SON-DP protein. This is assessed by the following parameters: If calculable, including but not limited to maximum plasma concentration (Cmax), trough concentration (Ctrough), time to reach maximum plasma concentration (tmax), and area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable concentration [AUC(0-last)], AUC from time zero to infinity Day 1 only, [AUC(0-inf)], and systemic clearance (CL), volume of distribution (Vz and Vss), terminal half-life (t1/2), terminal rate constant (lambda z), and measures of dose proportionality and accumulation.
Timepoint [2] 416991 0
Plasma PK endpoints include: Phase 1 a: - Cycle 1 - Week 1- Day 1- Pre-dose, End of infusion (EOI), 0.5 hours post EOI, 1 hour post EOI, 1.5 hours post EOI, 2 hours post EOI, 4 hours post EOI, 6 hours post EOI, Day 2 - 24 hours post EOI Day 4- 72 hours pre-dose, 72 hours post EOI, Week 2 -Day 8 - Pre-dose, EOI, Week 3 - Day 18 - Pre-dose, EOI, Week 4 - Day 25 - Pre-dose , EOI, Cycle 2- Week 1- Day 1- Pre-dose, EOI, 0.5 hours post EOI, 1 hour post EOI, 1.5 hours post EOI, 2 hours post EOI, 4 hours post EOI, 6 hours post EOI, Cycle 2- Week 1- Day 1- at the time of tumour biopsy. Cycle 3 - Week 1 and subsequent cycles up to Cycle 6 - Pre-dose, EOI
Secondary outcome [3] 416992 0
To characterize the PD of SON-DP through assessment of changes in tumour morphology - Changes in overall tumour morphology as assessed from a tumour biopsy on-treatment relative to a screening biopsy (using scales developed for this purpose).

Timepoint [3] 416992 0
Tumour biopsy is performed at Screening and Cycle 2 Week 1 for higher dose cohorts (2mg/kg or higher).
Secondary outcome [4] 416993 0
To assess the immunogenicity of SON-DP.
- Incidence of anti-drug antibodies (ADA)
Timepoint [4] 416993 0
Blood samples will be collected from all participants to determine ADA at screening, pre-dose on Day 1 of Cycle 1, pre-dose on Day 15 of Cycle 1, pre-dose on Day 25 of Cycle 1, pre-dose on Day 1 of subsequent cycles up to Cycle 6, and at EOT 30 days after last infusion.
Secondary outcome [5] 416994 0
Exploratory Outcome 1a: To assess presence of the SON-DP protein in tumour tissue.
Timepoint [5] 416994 0
Tumour biopsy performed at Screening and Cycle 2 week 1
Secondary outcome [6] 416995 0
Exploratory Outcome 2: To develop a method for detection of immunogenicity of polyethylenimine (PEI)
Timepoint [6] 416995 0
Blood samples will be collected from all participants to determine ADA at screening, pre-dose on Day 1 of Cycle 1, pre-dose on Day 15 of Cycle 1, pre-dose on Day 25 of Cycle 1, pre-dose on Day 1 of subsequent cycles up to Cycle 6 (even cycles), and at EOT 30 days after last infusion.
Secondary outcome [7] 416996 0
Exploratory Outcome 3a: To characterize the PD of SON-DP through assessment of development of transient pluripotent stem cells (tiPSCs) in tumour tissue biopsies.
Timepoint [7] 416996 0
Tumour biopsy performed at Screening and Cycle 2 week 1.
Secondary outcome [8] 416997 0
Exploratory Outcome 4a: To identify blood biomarkers for blood borne measures of SON-DP activity.
Timepoint [8] 416997 0
ctDNA is performed during Screening period and post dose on Cycle 1 - Week 4- Day 25 and subsequent cycles up to Cycle 6 on Week 4 Day 25.
Secondary outcome [9] 416998 0
Exploratory Outcome 5a: To monitor changes in tumour burden and somatic tumour mutations as reflected in ctDNA levels and genomic profile as a surrogate efficacy endpoint via blood samples.
Timepoint [9] 416998 0
Timepoints include:

- CtDNA is performed during Screening period and post dose on Cycle 1 - Week 4- Day 25 and subsequent cycles up to Cycle 6 on Week 4 Day 25.
Secondary outcome [10] 417898 0
To assess the anti-tumour activity of SON-DP administered as a monotherapy in subjects with relapsed/refractory/intolerant to standard of care therapies, for advanced/metastatic solid tumours. This will be assessed by the following.
ECOG performance status for any change in symptom burden.
Timepoint [10] 417898 0
ECOG performance status for any change in symptom burden - During Cycle 1, ECOG Scale of PS will be assessed on the day of drug administration, at EOT and as clinically indicated. During subsequent cycles up to Cycle 6, ECOG PS will be assessed on Day 1 of the cycle.
Secondary outcome [11] 418175 0
To characterize the plasma PK profile of the SON-DP protein Oct4. This is assessed by the following parameters:
If calculable, including but not limited to maximum plasma concentration (Cmax), trough concentration (Ctrough), time to reach maximum plasma concentration (tmax), and area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable concentration [AUC(0-last)], AUC from time zero to infinity Day 1 only, [AUC(0-inf)], and systemic clearance (CL), volume of distribution (Vz and Vss), terminal half-life (t1/2), terminal rate constant (lambda z), and measures of dose proportionality and accumulation.
Timepoint [11] 418175 0
Plasma PK endpoints include:
Phase 1 a:
- Cycle 1 - Week 1- Day 1- Pre-dose, End of infusion (EOI), 0.5 hours post EOI, 1 hour post EOI, 1.5 hours post EOI, 2 hours post EOI, 4 hours post EOI, 6 hours post EOI
Day 2 - 24 hours post EOI
Day 4- 72 hours pre-dose, 72 hours post EOI
Cycle 2- Week 1- Day 1- Pre-dose, EOI, 0.5 hours post EOI, 1 hour post EOI, 1.5 hours post EOI, 2 hours post EOI, 4 hours post EOI, 6 hours post EOI,
Cycle 2- Week 1- Day 1- at the time of tumour biopsy.
Cycle 3, Week 1 and subsequent cycles up to Cycle 6 - Pre-dose, EOI
Secondary outcome [12] 418177 0
To assess the immunogenicity of SON-DP proteins. - Incidence of anti-drug antibodies (ADA); antibody titers; potential neutralizing activity of the ADAs
Timepoint [12] 418177 0
Blood samples will be collected from all participants to determine ADA at screening, pre-dose on Day 1 of Cycle 1, pre-dose on Day 15 of Cycle 1, pre-dose on Day 25 of Cycle 1, pre-dose on Day 1 of subsequent cycles up to Cycle 6, and at EOT 30 days after last infusion.
Secondary outcome [13] 418179 0
Exploratory Outcome 1b: To assess presence of the SON-DP proteins in the tumour,
Timepoint [13] 418179 0
Biopsy samples will be evaluated for PD biomarkers and concentrations of SON-DP proteins. Tumour biopsy performed at Screening and Cycle 2 week 1
Secondary outcome [14] 418181 0
Exploratory Outcome 3b: To characterize the PD of SON-DP through assessment of changes in cell proliferation rates in tumour tissue biopsies. These are assessed by the following parameters:
• Evidence of normalization of p53 and related pathways in the on-treatment biopsy relative to the pre-treatment biopsy.

The participants at higher dose levels (greater or equal to 2 mg/kg) during Phase Ia dose escalation will be asked to provide fresh tissue at screening and in Week 1 of Cycle 2. No biopsy is required at later cycles. The ICF will include agreement to undergo biopsies and, if necessary, repeat biopsies should the sample prove inadequate.

Participants at dose level 3 can volunteer for biopsies at screening and Week 1 of Cycle 2.
Timepoint [14] 418181 0
Tumour biopsy performed at Screening and Cycle 2 week 1.
Secondary outcome [15] 418182 0
Exploratory Outcome 3c: To characterize the PD of SON-DP through assessment of DNA damage and lineage-specific (resident tissue) re-differentiation in tumour tissue biopsies. These are assessed by the following parameters:
• Lineage, proliferation, DNA damage and other biomarkers in tumour cell reprogramming

The participants at higher dose levels (greater or equal to 2 mg/kg) during Phase Ia dose escalation will be asked to provide fresh tissue at screening and in Week 1 of Cycle 2. No biopsy is required at later cycles. The ICF will include agreement to undergo biopsies and, if necessary, repeat biopsies should the sample prove inadequate.

Participants at dose level 3 can volunteer for biopsies at screening and Week 1 of Cycle 2.
Timepoint [15] 418182 0
Tumour biopsy performed at Screening and Cycle 2 week 1.
Secondary outcome [16] 418184 0
Exploratory Outcome 4b: To identify blood biomarkers for blood borne measures of SON-DP activity.
Timepoint [16] 418184 0
ctDNA is performed during Screening period and post dose on Cycle 1 - Week 4- Day 25 and subsequent cycles up to Cycle 6 on Week 4 Day 25.
Secondary outcome [17] 418185 0
Exploratory Outcome 5b: To monitor changes in tumour burden and somatic tumour mutations as reflected in ctDNA levels and genomic profile as a surrogate efficacy endpoint via blood samples. These are assessed by the following parameters:
- To monitor changes in tumour burden and somatic tumour mutations as reflected in total mutation burden.
Timepoint [17] 418185 0
Timepoints include:

- CtDNA is performed during Screening period and post dose on Cycle 1 - Week 4- Day 25 and subsequent cycles up to Cycle 6 on Week 4 Day 25.
Secondary outcome [18] 418189 0
Exploratory Outcome 5c: To monitor changes in tumour burden and somatic tumour mutations as reflected in ctDNA levels and genomic profile as a surrogate efficacy endpoint via blood samples.
Timepoint [18] 418189 0
Timepoints include:

- CtDNA is performed during Screening period and post dose on Cycle 1 - Week 4- Day 25 and subsequent cycles up to Cycle 6 on Week 4 Day 25.
Secondary outcome [19] 418662 0
[Primary Outcome 4]: To determine the Recommended Phase II Dose (RP2D).

Determination of the RP2D based on DLTs during Cycle 1 (i.e., 28-day cycle). The RP2D will be determined using Cycle 1 information as well as available subsequent SON-DP treatment information.

For the dose level considered as a potential RP2D, at least 8 weeks of treatment/follow-up of the lastsubject treated (to allow for tumour imaging data to become available) will be necessary for the SMC tofi nalise its RP2D determination.
Timepoint [19] 418662 0
[Primary Timepoint 4]:
The timepoints include:
The SMC will consider data available from all treatment cycles and will additionally, consider PK data, PDdata, both from blood and biopsy samples and available anti-tumour activity to determine the RP2D.

Eligibility
Key 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


Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Sponsor decision to terminate study in Australia due to business strategy changes
Date of first participant enrolment
Anticipated
28/07/2023
Actual
Date of last participant enrolment
Anticipated
25/09/2025
Actual
Date of last data collection
Anticipated
25/04/2026
Actual
Sample size
Target
48
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 312651 0
Commercial sector/Industry
Name [1] 312651 0
Qurgen Australia Pty Ltd
Country [1] 312651 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Qurgen Australia Pty Ltd
Address
Qurgen Australia Pty Ltd
Level 5, 63 Pirie Street,
Adelaide, SA, 5000 Australia
Country
Australia
Secondary sponsor category [1] 314258 0
Commercial sector/Industry
Name [1] 314258 0
Avance Clinical Pty Ltd
Address [1] 314258 0
Avance Clinical Pty Ltd
Level 1, 2 Ann Nelson Drive
Thebarton, SA 5031, Australia
Country [1] 314258 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311958 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 311958 0
Ethics committee country [1] 311958 0
Australia
Date submitted for ethics approval [1] 311958 0
21/12/2022
Approval date [1] 311958 0
13/02/2023
Ethics approval number [1] 311958 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122966 0
Dr Dr Ganessan Kichenadasse
Address 122966 0
Southern Oncology Clinical Research Unit (SOCRU)
Level 3, Mark Oliphant Building, 5 Laffer Drive, Bedford Park, SA, 5042
Country 122966 0
Australia
Phone 122966 0
+61 491679039
Fax 122966 0
Email 122966 0
[email protected]
Contact person for public queries
Name 122967 0
Dr Ganessan Kichenadasse
Address 122967 0
Southern Oncology Clinical Research Unit (SOCRU)
Level 3, Mark Oliphant Building, 5 Laffer Drive, Bedford Park, SA, 5042
Country 122967 0
Australia
Phone 122967 0
+61 491679039
Fax 122967 0
Email 122967 0
request by site
Contact person for scientific queries
Name 122968 0
Dr Meidong Zhu
Address 122968 0
Qurgen Australia Pty Ltd
Level 5, 63 Pirie Street,
Adelaide, SA, 5000 Australia
Country 122968 0
Australia
Phone 122968 0
+61 484714378
Fax 122968 0
Email 122968 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and Intellectual property considerations


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.