Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000798662
Ethics application status
Approved
Date submitted
4/05/2023
Date registered
26/07/2023
Date last updated
30/08/2024
Date data sharing statement initially provided
26/07/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A First-in-Human, Open-label, Phase 1/2 Study of BOS-342 in Patients with Hepatocellular Carcinoma (HCC) and other Glypican 3 (GPC3)-expressing Tumors
Scientific title
A Phase 1/2, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of BOS-342 in Patients with Hepatocellular Carcinoma (HCC) and other GPC3-expressing Tumors
Secondary ID [1] 309314 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
HCC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma (HCC) 329505 0
Other GPC3-expressing Tumors 330453 0
Condition category
Condition code
Cancer 326439 326439 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BOS-342 (formerly known as PRS-342 and MPAL1073) is a monoclonal antibody (mAb)-like bispecific protein targeting the tumor antigen Glypican 3 (GPC3) and the costimulatory immunoreceptor 4-1BB (CD137). The anticipated mode of action of BOS-342 is to combine GPC3 binding in the tumor microenvironment with 4-1BB-induced T cell co-stimulation and expansion, leading to a higher local T cell activation and a reduced risk of systemic toxicity compared to monospecific 4-1BB targeting.

BOS-342 will be administered intravenously (IV) every 2 weeks (Q2W) until radiologically documented progressive disease (PD), unacceptable toxicity, or occurrence of any criterion for withdrawal from the study or the study treatment. Additional dosing schedules may be explored based on available pharmacokinetics (PK), Pharmacodynamics (PD) and clinical activity.

The study is comprised of 2 phases. Phase 1 is to assess the safety of BOS-342 and determine the maximum tolerated dose and/or recommended Phase 2 dose of BOS-342. Phase 2 is to evaluate the response rate in patients treated with BOS-342.

- Phase 1 (dose escalation): Small groups of participants will be enrolled one at a time. The next group will receive a higher dose of BOS-342 bi-weekly if the previous group tolerated a lower dose. These groups will be enrolled until the highest tolerated dose of BOS-342 is identified. Additional participants may be enrolled in previously cleared dose levels while some participants may be treated at higher dose levels.
- Phase 2 (dose expansion): Larger group of participants will be enrolled into the dose group selected from Phase 1. This group will receive a dose level and schedule that is deemed safe and tolerable as determined in Phase 1. Phase 2 is for collecting more information about the selected dose.

A single treatment cycle is 28 days long, with BOS-342 administered intravenously (IV) on Day 1 and Day 15 of each cycle. The starting dose of BOS-342 (Dose Level 1) is 0.5 mg/kg intravenously (IV) every two weeks (Q2W). Dose escalation decisions will be based on the safety review of data collected in Cycle 1 (dose-limiting toxicity [DLT] period). Six Doses (intravenously, every two weeks) are planned to be assessed for Phase 1: (Dose Level 1) is 0.5 mg/kg, (Dose Level 2) is 1.5 mg/kg, (Dose Level 3) is 4.5 mg/kg, (Dose Level 4) is 9 mg/kg, (Dose Level 5) is 18 mg/kg and (Dose Level 6) is 27 mg/kg.

Once the DLT period is met (28 days) for all patients enrolled to the evaluating-dose cohort, potential patients for the next cohort can begin screening. Once the safety data for the evaluating-dose cohort is evaluated by the Safety Review Team (SRT) and the decision is made to continue enrolling patients to the next dose cohort, patients can be treated at the dose determined by the SRT.
Intervention code [1] 325750 0
Treatment: Drugs
Comparator / control treatment
NA
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334283 0
Phase 1 - To assess the safety of BOS-342 and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BOS-342

• Occurrence of dose-limiting toxicities (DLTs) .
• Incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and Grade 3 or higher TEAEs.
• Incidence and shifts of clinically significant clinical laboratory abnormalities.
• Change from baseline in other observations related to safety, including electrocardiograms (ECGs), vital signs, and Karnofsky performance status.

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 (CTCAE) V5.0 dated 27Nov2017.
- Vital signs- Blood pressure will be measured using sphygmomanometer, body temperature will be measured using a thermometer, Heart rate (HR) will be measured using vital sign machine and respiratory rate using pulse oximetry.
- ECG- A single standard 12-lead electrocardiogram (ECG) will be recorded after the patient has been resting for at least 5 minutes in the supine position and before any blood sample collection required at the same timepoint, as specified in the Schedule of Activities (SoA) using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval (QTc) intervals.
- Echocardiogram - Ejection fraction is to be determined by echocardiogram, MUGA or cardiovascular MRI during Screening.
- Clinical laboratory tests - (Blood – including Hematology, Chemistry, Coagulation, Serology and Urine analysis)
- Karnofsky Performance- will be assessed by the treating investigator.
Timepoint [1] 334283 0
Phase 1:
• Occurrence of dose-limiting toxicities (DLTs) - assessed at all scheduled visits post dosing.
• Incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and Grade 3 or higher TEAEs - assessed at all visits post dosing.
• Incidence and shifts of clinically significant clinical laboratory abnormalities - reviewed at all scheduled visits.
• Change from baseline in other observations related to safety, including electrocardiograms (ECGs), vital signs, and Karnofsky performance status - ECG reviewed at C1D1 and at C2D1, Vitals and Karnofsky performance status at all visits.

The timepoints include:

- Adverse events (AEs) - AEs assessment will be performed at each visit throughout the study period from Screening through to 30 Days after last infusion of study drug (Follow Up/End of Treatment (EOT) Visit).
- Vital Signs - Vital Signs are performed during Screening, Cycle 1- Days 1, 8, 15 and 22 and all other cycles on Days 1 and 15, EoT and safety follow up. Vital signs will be measured in a supine position after 5 minutes rest and should be assessed predose (within 15 minutes of infusion), and then every 15 minutes from the start of infusion continuing through the duration of the infusion. If vital signs are not stable after completion of the infusion, vitals will be monitored every 15 minutes until stable on 2 consecutive repeated measurements. Otherwise, subsequent vital signs will be taken every 60 minutes until 4 hours following completion of the infusion. If there are no clinically significant changes in vital signs during the first 2 infusions then the vital signs schedule for subsequent infusions will be predose, every 15 minutes during the infusion, and then 1 hour from completion of infusion.
- ECG- Electrocardiograms will be performed on Cycle 1 Day 1 and Cycle 2 Day 1 predose and within 15 minutes following the end of infusion and as clinically indicated. Whenever ECG and blood / PK samples are specified to be collected at the same time, ECG will be obtained before the blood / PK sampling.
- Laboratory tests- Haematology and chemistry tests will be performed pre-infusion at Screening, Days 1, 8, 15 and 22 of Cycle 1, Days 1 and 15 of each subsequent cycle, and at the EOT visit and follow up visit.
Urinalysis should be obtained pre-infusion at Screening, Days 1, 8, 15 and 22 of Cycle 1, Day 1 of each subsequent cycle, and at the EOT and safety follow up visit.
Coagulation samples will be obtained pre-infusion at Screening, at Day 1 of each cycle, at EOT and at Safety Follow-Up Visits.
- Karnofsky performance status for any change in symptom burden – Karnofsky Scale of PS will be assessed at Screening, Cycle 1: Days 1, 8, 15 and 22 and all other cycles on days 1 and 15 (day of drug administration), EoT and safety follow up and as clinically indicated.
Primary outcome [2] 334289 0
Phase 2 - To evaluate the response rate in patients treated with BOS-342

• Confirmed Objective response rate (ORR) per RECIST 1.1
Timepoint [2] 334289 0
Phase 2: Response rate is evaluated every 8 weeks and at EOT.

Response rate is evaluated every 8 weeks until the subject comes off the treatment and at EOT. Imaging assessments - CT or MRI scans conducted at Screening and every 8 weeks until the subject comes off the treatment and at EoT. In the absence of radiologic progression, tumour assessments should continue regardless of 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.
Primary outcome [3] 334290 0
Phase 2 - To evaluate the safety and tolerability of BOS-342

• Incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and Grade 3 or higher TEAEs
• Incidence and shifts of clinically significant clinical laboratory abnormalities
• Change from baseline in other observations related to safety, including ECGs, vital signs, and Karnofsky performance status

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 (CTCAE) V5.0 dated 27Nov2017.
- Vital signs- 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 using pulse oximetry.
- ECG- A single standard 12-lead electrocardiogram (ECG) will be recorded after the patient has been resting for at least 5 minutes in the supine position and before any blood sample collection required at the same timepoint, as specified in the Schedule of Activities (SoA) using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval (QTc) intervals.
- Echocardiogram - Ejection fraction is to be determined by echocardiogram, MUGA or cardiovascular MRI during Screening.
- Clinical laboratory tests - (Blood – including Hematology, Chemistry, Coagulation, Serology and Urine analysis)
- Karnofksy Performance- will be assessed by the treating investigator.
Timepoint [3] 334290 0
Phase 2:
• Incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and Grade 3 or higher TEAEs- Evaluated at each scheduled visit.
• Incidence and shifts of clinically significant clinical laboratory abnormalities - evaluated at each scheduled visit.
• Change from baseline in other observations related to safety, including ECGs, vital signs, and Karnofsky performance status- ECG reviewed at C1D1 and at C2D1, Vitals and Karnofsky performance status at all visits.

The timepoints include:

- Adverse events (AEs) - AEs assessment will be performed at each visit throughout the study period from Screening through to 30 Days after last infusion of study drug (Follow Up/End of Treatment (EOT) Visit).
*- Vital Signs - Vital Signs are performed during Screening, Cycle 1- Days 1, 8, 15 and 22 and all other cycles on days 1 and 15, EoT and safety follow up. Vital signs will be measured in a supine position after 5 minutes rest and should be assessed predose (within 15 minutes of infusion), and then every 15 minutes from the start of infusion continuing through the duration of the infusion. If vital signs are not stable after completion of the infusion, vitals will be monitored every 15 minutes until stable on 2 consecutive repeated measurements. Otherwise, subsequent vital signs will be taken every 60 minutes until 4 hours following completion of the infusion. If there are no clinically significant changes in vital signs during the first 2 infusions then the vital signs schedule for subsequent infusions will be predose, every 15 minutes during the infusion, and then 1 hour from completion of infusion.
- ECG- Electrocardiograms will be performed on Cycle 1 Day 1 and Cycle 2 Day 1 predose and within 15 minutes following the end of infusion and as clinically indicated. Whenever ECG and blood / PK samples are specified to be collected at the same time, ECG will be obtained before the blood / PK sampling.
- Laboratory tests- Haematology and chemistry tests will be performed pre-infusion at Screening, Days 1, 8, 15 and 22 of Cycle 1, Days 1 and 15 of each subsequent cycle, and at the EOT visit and follow up visit.
Urinalysis should be obtained pre-infusion at Screening, Days 1, 8, 15 and 22 of Cycle 1, Day 1 of each subsequent cycle, and at the EOT and safety follow up visit. Coagulation samples will be obtained pre-infusion at Screening and at Day 1 of Cycle 2.
- Karnofsky performance status for any change in symptom burden – Karnofsky Scale of PS will be assessed at Screening, Cycle 1: Days 1, 8, 15 and 22 and all other cycles on days 1 and 15 (day of drug administration), EoT and safety follow up and as clinically indicated.
Secondary outcome [1] 420118 0
Phase 1 - To assess the serum PK profile of BOS-342

PK parameters for BOS-342 such as, but not limited to, maximum serum concentration (Cmax), time to maximum serum concentration (Tmax), and area under the serum concentration versus time curve from time 0 to t (AUC0–t)
Timepoint [1] 420118 0
Phase 1: PK parameters for BOS-342 such as, but not limited to, maximum serum concentration (Cmax), time to maximum serum concentration (Tmax), and area under the serum concentration versus time curve from time 0 to t (AUC0–t)- evaluated by collecting PK samples as Pre-dose (samples collected at C1D1; C2D15: C3D1; C4D1; C5D1) and post dose samples collected at C1 and C2 at variable timepoints.

Samples for pharmacokinetics and bioanalytical assessment will be collected as per the PK and bioanalytical blood sample collection schedule at all scheduled cycle visits on Cycle 1 Day 1- less than 1 hour prior to drug infusion,, post-dose at End of Infusion (EOI), 1, 3, 6 and on days 2 (24h post End of Infusion (EOI), 3 (48h post EOI), 4 (72h post EOI), 8 (168h post EOI) and 15 (336h post EOI). Cycle 2 Day 15- less than 1 hour prior to drug infusion, post-dose at End of Infusion (EOI), 1, 3, 6 and on days 16 (24h post EOI), 17 (48h post EOI), 18 (72h post EOI) and 22 (168h post EOI). Day 1 of Cycle 3 and subsequent cycles up to Cycle 10 – less than 1 hour Pre-dose, and post-dose at 1 hour post End of Infusion (EOI). Schedule may be altered on the basis of evolving data.
Secondary outcome [2] 420147 0
Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Duration of Response (DOR) per RECIST 1.1
Timepoint [2] 420147 0
Phase 2:
• DOR per RECIST 1.1 - assessed every 8 weeks, until subject comes off treatment and at EoT. For patients who discontinued BOS-342 not due to a radiologic PD, tumor assessment should be performed until a radiologic PD is observed or a new anti cancer therapy is initiated or death whichever comes first.
Secondary outcome [3] 420148 0
Phase 2 - To assess the serum PK profile of BOS-342

• PK parameters for BOS-342 such as, but not limited to, Cmax, Tmax, and AUC0–t
Timepoint [3] 420148 0
Phase 2:
• PK parameters for BOS-342 such as, but not limited to, Cmax, Tmax, and AUC0–t - evaluated by collecting PK samples as Pre-dose (samples collected at C1D1; C2D15; Day 1 of C3 to C10) and post dose samples collected at from C1 to C10 at variable timepoints.

Samples for pharmacokinetics and bioanalytical assessment will be collected as per the PK and bioanalytical blood sample collection schedule at all scheduled cycle visits on Cycle 1 Day 1- less than 1 hour prior to drug infusion, post-dose at End of Infusion (EOI), 1, 3, 6 and on days 2 (24h post End of Infusion (EOI), 3 (48h post EOI), 4 (72h post EOI), 8 (168h post EOI) and 15 (336h post EOI). Cycle 2 Day 15- less than 1 hour prior to drug infusion, post-dose at End of Infusion (EOI), 1, 3, 6 and on days 16 (24h post EOI), 17 (48h post EOI), 18 (72h post EOI) and 22 (168h post EOI). Day 1 of Cycle 3 and subsequent cycles up to Cycle 10 – less than 1 hour Pre-dose, and post-dose at 1 hour post End of Infusion (EOI). Schedule may be altered on the basis of evolving data.
Secondary outcome [4] 423379 0
Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Confirmed ORR per iRECIST
Timepoint [4] 423379 0
Phase 2:
• Confirmed ORR per iRECIST - assessed every 8 weeks, until subject comes off treatment and at EoT. For patients who discontinued BOS-342 not due to a radiologic PD, tumor assessment should be performed until a radiologic PD is observed or a new anti cancer therapy is initiated or death whichever comes first.
Secondary outcome [5] 423380 0
Phase 2 - To assess antitumor activity in patients treated with BOS-342

• Overall survival
Timepoint [5] 423380 0
Phase 2:
• Overall survival- assessed every 3 months post EOT.
Secondary outcome [6] 423902 0
Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Time-to-response (TTR) per RECIST 1.1
Timepoint [6] 423902 0
Phase 2:
• TTR per RECIST 1.1 - assessed every 8 weeks, until subject comes off treatment and at EoT. For patients who discontinued BOS-342 not due to a radiologic PD, tumor assessment should be performed until a radiologic PD is observed or a new anti cancer therapy is initiated or death whichever comes first.
Secondary outcome [7] 423903 0
Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Disease control rate (DCR) per RECIST 1.1
Timepoint [7] 423903 0
Phase 2:
• DCR per RECIST 1.1 - assessed every 8 weeks, until subject comes off treatment and at EoT. For patients who discontinued BOS-342 not due to a radiologic PD, tumor assessment should be performed until a radiologic PD is observed or a new anti cancer therapy is initiated or death whichever comes first.
Secondary outcome [8] 423904 0
Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Progression-free survival (PFS) per RECIST 1.1
Timepoint [8] 423904 0
Phase 2:
• PFS per RECIST 1.1 - assessed every 8 weeks, until subject comes off treatment and at EoT. For patients who discontinued BOS-342 not due to a radiologic PD, tumor assessment should be performed until a radiologic PD is observed or a new anti cancer therapy is initiated or death whichever comes first.
Secondary outcome [9] 423905 0
Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Confirmed DOR per iRECIST
Timepoint [9] 423905 0
Phase 2:
• Confirmed DOR per iRECIST - assessed every 8 weeks, until subject comes off treatment and at EoT. For patients who discontinued BOS-342 not due to a radiologic PD, tumor assessment should be performed until a radiologic PD is observed or a new anti cancer therapy is initiated or death whichever comes first.
Secondary outcome [10] 423906 0
Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Confirmed TTR per iRECIST
Timepoint [10] 423906 0
Phase 2:
• Confirmed TTR per iRECIST - assessed every 8 weeks, until subject comes off treatment and at EoT. For patients who discontinued BOS-342 not due to a radiologic PD, tumor assessment should be performed until a radiologic PD is observed or a new anti cancer therapy is initiated or death whichever comes first.
Secondary outcome [11] 423907 0
Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Confirmed DCR per iRECIST
Timepoint [11] 423907 0
Phase 2:
• Confirmed DCR per iRECIST - assessed every 8 weeks, until subject comes off treatment and at EoT. For patients who discontinued BOS-342 not due to a radiologic PD, tumor assessment should be performed until a radiologic PD is observed or a new anti cancer therapy is initiated or death whichever comes first.
Secondary outcome [12] 423908 0
Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Confirmed PFS per iRECIST
Timepoint [12] 423908 0
Phase 2:
• Confirmed PFS per iRECIST - assessed every 8 weeks, until subject comes off treatment and at EoT. For patients who discontinued BOS-342 not due to a radiologic PD, tumor assessment should be performed until a radiologic PD is observed or a new anti cancer therapy is initiated or death whichever comes first.

Eligibility
Key inclusion criteria
Age
1. Patients must be greater than or equal to 18 years, at the time of signing the informed consent.
Disease Characteristics
2. Histologically confirmed diagnosis of locally advanced, unresectable or metastatic HCC for which no standard curative therapy is available, or ineligible to accept/unable to tolerate standard therapy.
3. At least 1 unidimensional radiographically measurable lesion based on RECIST 1.1.
4. Availability of tumor biopsy:
• Phase 1 only: availability of a fresh biopsy or archival tumor samples no older than 2 years prior to the first study drug administration. Tumor biopsies and tumor archival material must be suitable for biomarker assessment (at least 10 slides). Patients who do not have adequate archival tissue will require a biopsy during the screening period. Refer to the Laboratory Manual for further information.
• Phase 2 only: availability of fresh tumor biopsy, or an archival tumor sample taken after the last anticancer treatment and prior to the first study drug administration. Tumor biopsies and tumor archival material must be suitable for biomarker assessment (at least 10 slides). Patients who do not have adequate archival tissue will require a biopsy during the screening period. Refer to the Laboratory Manual for further information.
5. GPC3 Expression:
• Tumor samples are positive for GPC3 by local or central immunohistochemistry testing

Organ Function and Performance Score within 10 days of treatment initiation
6. Karnofsky score greater than or equal to 50.
7. Adequate renal function as defined by an estimated creatinine clearance of greater than or equal to 60 mL/min/1.73 m2 according to the Cockcroft-Gault equation.
8. Adequate hepatic function defined as:
• total bilirubin less than or equal to 1.5 × upper limit of normal (ULN) or normal conjugated bilirubin.
• aspartate aminotransferase [AST] and alanine aminotransferase [ALT] less than or equal to 3 × ULN, or less than or equal to 5 × ULN if due to liver involvement by tumor.
9. Adequate bone marrow function defined as:
• absolute neutrophil count greater than or equal to 1..5 × 109 cells/L.
• hemoglobin greater than or equal to 9.0 g/dL.
• platelets greater than or equal to 75 × 109 cells/L.
10. Adequate cardiac function defined as ejection fraction greater than 50% by echocardiogram, multigated acquisition (MUGA) or cardiovascular magnetic resonance imaging (MRI).

Pregnancy and Contraception
11. All patients must be willing and able to comply with a highly effective contraceptive method (Appendix 4) during and for 3 months after the treatment period. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Informed Consent
12. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol prior to initiation of any study procedures.
13. Willing and able to participate in the study and comply with all study requirements.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Cancer and Previous Cancer Therapy
1. Any persistent clinically significant greater than or equal to Grade 2 toxicity from prior cancer therapy except alopecia or sensory neuropathy or immunotherapy-related thyroid toxicity requiring replacement therapy.
2. Active CNS metastasis.
Exceptions: patients with stable brain metastases previously treated with surgery, radiotherapy or systemic therapy who are on a stable dose of steroids/anticonvulsants, with no dose change within 28 days prior to the first dose of study drug, are eligible to enroll. CNS lesions that have been radiated should not be selected as target lesions for the purposes of RECIST evaluation.
3. Cancer directed therapy (chemotherapy, radiotherapy, biologic, immunotherapy, hormonal therapy or other) within the shorter of 28 days or 5 half-lives, if known, of the first dose of study drug.
Exception: palliative radiotherapy is allowed within 28 days prior to initiating treatment if associated toxicity resolved to less than or equal to Grade 1. However, lesions treated palliatively should not be selected as target lesions unless there has been clear progression of those lesions since the end of that treatment.
4. Prior or concurrent malignancy other than the malignancy under study, within the last 3 years.
Exception: Patients with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma or other malignancy for which there is very low risk of recurrence or progression are eligible.

Prior/Concomitant Therapy
5. Major surgery within 28 days prior to the first dose of study drug.
6. Systemic corticosteroid therapy or any other form of systemic immunosuppressive medication within 1 week prior to the first dose of study drug.
Exceptions: corticosteroid use as a premedication for IV contrast, transfusion therapy or prednisone less than or equal to 10 mg or equivalent per day for adrenal replacement or for patients with CNS disease, is permitted.
7. Live vaccine within 30 days prior to first day of treatment.

Infections
8. Active hepatitis B, defined as hepatitis B virus (HBV) surface antigen positive and HBV core antibody positive with positive HBV deoxyribonucleic acid (DNA), or HBV positive core antibody alone with positive HBV DNA, unless meeting all of the following criteria:
- Stable on antiviral therapy for hepatitis B virus (HBV) for at least 12 weeks.
- Adherence to antiviral therapy during study therapy per local standard of care.
- HBV viral load less than 200 IU / ml at screening
9. Active hepatitis C, defined as positive hepatitis C virus (HCV) antibody with positive HCV ribonucleic acid (RNA).
10. Known infection with human immunodeficiency virus (HIV), unless meeting all of the following criteria:
• Stable on antiretroviral therapy (ART) for at least 4 weeks.
• Adherence to ART during study therapy.
• HIV viral load of less than 400 copies/mL at Screening (or undetectable per local criteria).
• CD4 counts greater than or equal to 200/microliter.
11. Evidence or history of active or latent tuberculosis (TB) infection, defined as any 1 of the following:
• Current clinical, radiographical, or laboratory evidence of active TB.
• History of active TB.
• Positive QuantiFERON-TB Gold In-Tube or other diagnostic test in the absence of clinical manifestations.
12. Active uncontrolled infection being treated with systemic antibiotic, antiviral, or antifungal therapy.

Pregnancy and Breastfeeding
13. Pregnancy: Negative serum pregnancy test for females of child-bearing potential are required within 48 hours before the first dose of study intervention.
14. Breastfeeding or storage of breast milk.

Organ Function
15. Uncontrolled or significant cardiovascular disease, including:
• myocardial infarction, unstable angina or stroke/transient ischemic attack within the past 6 months.
• history of clinically significant arrythmias (such as atrial fibrillation, ventricular tachycardia, ventricular fibrillation or torsade de pointes).
• history of other clinically significant heart disease (e.g., New York Heart Association (NYHA) Class II or greater congestive heart failure, pericarditis, cardiac amyloidosis, significant pericardial effusion).
16. Liver cirrhosis classified as Child-Pugh Class B (greater than 7) or C.

Concurrent Conditions
17. Uncontrolled or severe concurrent medical condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate. Any patient who experiences a Grade 3 or higher AE during the screening period needs to be discussed with the Medical Monitor and Sponsor to confirm eligibility.
18. Uncontrolled intercurrent illness or psychiatric illness/social situation that would limit compliance with study requirements.
19. Clinically significant autoimmune disease, or history of greater than or equal to Grade 3 immune-mediated adverse event due to a checkpoint inhibitor or similar therapy.
20. Solid organ transplant.

Other Exclusions
21. Patient not available to complete all protocol required study visits or procedures to the best of the patient’s ability and Investigator’s knowledge.
22. History or evidence of any other clinically significant condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator, would be a risk to patient safety or interfere with the study evaluation, procedures, or completion.

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)
Nil
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Nil
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Nil
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
Continuous measures will be summarized using number of patients with an observation(s),
mean, median, standard deviation, Q1 and Q3 quartiles, minimum and maximum value. Categorical measures will be summarized by number and percentage of patients per category.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/08/2023
Actual
2/08/2023
Date of last participant enrolment
Anticipated
23/10/2025
Actual
Date of last data collection
Anticipated
31/10/2026
Actual
Sample size
Target
81
Accrual to date
12
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 24363 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 24364 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 24595 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 39947 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 39948 0
5042 - Bedford Park
Recruitment postcode(s) [3] 40190 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 25591 0
Korea, Republic Of
State/province [1] 25591 0
South Korea

Funding & Sponsors
Funding source category [1] 313510 0
Commercial sector/Industry
Name [1] 313510 0
Boston Pharmaceuticals, Inc.
Country [1] 313510 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Boston Pharmaceuticals, Inc.
Address
Boston Pharmaceuticals, Inc.
55 Cambridge Parkway,
Suite 400 Cambridge,
MA 02142 USA
Country
United States of America
Secondary sponsor category [1] 315282 0
Commercial sector/Industry
Name [1] 315282 0
Allucent (Au) Pty. Ltd
Address [1] 315282 0
Pharm-Olam International Pty. Ltd.
Level 12, 60 Castlereagh Street
Sydney, NSW 2000
Country [1] 315282 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312695 0
Bellberry Human Reasearch Ethics Committee
Ethics committee address [1] 312695 0
Ethics committee country [1] 312695 0
Australia
Date submitted for ethics approval [1] 312695 0
29/03/2023
Approval date [1] 312695 0
29/05/2023
Ethics approval number [1] 312695 0

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

Contacts
Principal investigator
Name 125590 0
A/Prof Hao-Wen Sim
Address 125590 0
St Vincent's Hospital Sydney
370 Victoria Street,
Darlinghurst, NSW 2010
Country 125590 0
Australia
Phone 125590 0
+61 2 9355 5737
Fax 125590 0
Email 125590 0
hao-wen.sim@svha.org.au
Contact person for public queries
Name 125591 0
Harmeet Singh
Address 125591 0
Allucent (Au) Pty. Ltd., Level 12 60 Castlereagh Street Sydney, New South Wales 2000 AUSTRALIA
Country 125591 0
Australia
Phone 125591 0
+61 2 8358 1558
Fax 125591 0
Email 125591 0
harmeet.singh@allucent.com
Contact person for scientific queries
Name 125592 0
Jerry Huang, MD, PhD, MBA
Address 125592 0
Clinical Development Consultant, Boston Pharmaceuticals 55 Cambridge Parkway, Suite 400 Cambridge, MA 02142
Country 125592 0
United States of America
Phone 125592 0
+1 201 257 7534
Fax 125592 0
Email 125592 0
jerry.huang@bostonpharmaceuticals.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The data collected for each participant will be recorded and reported in a blinded manner, hence, it is not possible to provide individual participant data to be shared.


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.