RecruitingPhase 1ACTRN12622001339741

A First-in-Human Study to Evaluate the Safety and Tolerability of HH3806 in Patients With Advanced Tumors

A Phase I, Open-label, Multicenter, First in Human Study to Evaluate the Safety and Tolerability of HH3806 in Patients with Advanced Malignancies

Sponsor

Tigermed Australia Pty Ltd

Enrollment

36 participants

Start Date

Mar 13, 2023

Study Type

Interventional

Conditions

Solid Tumors relapsed/refractory Non-Hodgkin’s lymphomas (NHL)

Summary

This is a first in human study of a new potential treatment drug HH3806 for patients with relapsed/refractory NHL or advanced solid tumors. This study aims to determine the maximum safest dose of HH3806 that may be administered to cancer patients as a single therapy. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and to determine maximum safest dose of HH3806 that will be administered orally as a single therapy in adult patients with advanced malignancies. Who is it for? You may be eligible for this study if you are an adult aged 18 or older and you have been diagnosed with relapsed/refractory NHL or advanced solid tumors. Study details This study will be conducted for eleven dose levels. Participant will receive HH3806 once daily till disease progression. HH3806 capsule will be administered as an oral capsule once daily for the duration of each 28-day treatment cycle without any study treatment interruption between each cycle. All participants will undergo additional tests (including blood tests, echocardiograms and imaging) to assess the effect of the treatment on their cancer, and to monitor for side effects. Study participation for each participant could be continued until disease progression, unacceptable toxicity, death or withdrawal of consent until the date of the last data collection (1 year post-treatment commencement), whichever occurs first. A Safety Review Committee (SRC) consisting of the Investigators and the Sponsor’s designated representatives will monitor safety throughout the study and make dose escalation decisions (including any decisions to explore intermediate, higher, or lower doses and/or alternative dosing schedules). It is hoped that this research will demonstrate the safety of HH3806 and find the ideal dose for larger-scale studies.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria9

Male and female patients 18years of age or older .
Provide informed consent voluntarily prior to initiation of any study-related procedures.
Tumor type criteria: Histologically or cytologically confirmed diagnosis of one of the following advanced malignancy:
a) Solid tumors that meet the following criteria:
Measurable disease by RECIST v1.1 in at least 1 site with the exception of Castration-Resistant Prostate Cancer (CRPC), who may be enrolled with objective evidence of disease as per certain criteria; disease progression with the last line of therapy and at least one prior standard of care regimens, or for which there is no approved therapy, or for which standard therapy is unsuitable or refused. Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent. Patients without treatment options available known to provide clinical benefit are also eligible
b) Relapsed/refractory NHL must have received at least 2 prior systemic therapies and there is no standard salvage regimen available.
Life expectancy greater than or equal to 3 months.
ECOG performance status less than or equal to 1.
Patient must have adequate organ function measured within 28 days of screening.

Exclusion Criteria26

Patients are ineligible for this study if they meet any of the following criteria:
Anticancer therapy (including chemotherapy, targeted therapy, biotherapy, hormone therapy, traditional Chinese medication with cancer indication or other investigational agents) within 4 weeks or 5 times of half-lives (whichever is shorter) prior to the first dose of the study drug.
Patients who had prior treatment with any BET inhibitor.
Radical radiation therapy within 4 weeks prior to the first dose of the investigational product or received local palliative radiation therapy for bone metastases within 2 weeks.
Any toxicities from prior treatment that have not recovered to baseline or less than or equal to NCI-CTCAE v5.0 Grade 1 before the start of study treatment, except for Adverse Events not considered a likely safety risk.
Patients who have been treated with any hematopoietic colony-stimulating growth factors 2 weeks prior to starting study drug.
Patients who have symptomatic CNS metastasis which is neurologically unstable or those who have CNS disease requiring increase in the dose of steroid. (Note: Patients with controlled CNS metastasis can participate in the trial. Before entering the study, patients should have finished radiotherapy, or have received operation for CNS tumor metastasis at least two weeks before. Patients’ neurological function must be in a stable state; no new neurological deficit is found during clinical examination and no new abnormality is found during CNS imaging examinations. If patients need to use steroids to treat CNS metastasis, the therapeutic dose of steroid should be stable for 3 months at least two weeks prior to entering the study with treatment dose no more than dexamethasone 4 mg daily or an equivalent dose of steroids).
Major surgery or had significant traumatic injury within 28 days prior to the first dose of the investigational product or has not recovered from major side effects.
Patients with prior immunodeficiency, or organ transplantation or patients after allogeneic stem cell transplantation if they are less than 100 days has elapsed from the day of transplantation, they are on any treatment for graft-versus-host disease, or they have not been off calcineurin inhibitors for at least 4 weeks are excluded.
Patients diagnosed with cataract who have not undergone surgery and do not meet either of the following conditions: best corrected visual acuity greater than or equal to 0.6, Postmydriatic LOCS III lens opacity classification criteria: posterior subcapsular (P) = 0, cortex (C) less than or equal to 2, nuclear (N) less than or equal to 2.
Known HIV.
Active hepatitis B and hepatitis C.
Patients with clinically significant cardiovascular disease.
Any active malignancy 2 years before the first dose of study drugs, except for the specific cancer under investigation and any locally recurring cancer that has been treated with curative intent.
Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication 14 days before the first dose of study drugs.
Unable or unwilling to swallow study medication or gastrointestinal condition which could impair absorption of study medication.
Patient has any other concurrent severe and/or uncontrolled medical condition such as active infection, unresolved bowel obstruction, or psychiatric disorders that would, in the investigator’s judgment, contraindicate patient participation in the clinical study.
Patients with a history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, noninfectious pneumonitis, or uncontrolled lung diseases, including but not limited to pulmonary fibrosis, acute lung disease, etc.
Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc.
Activity gastrointestinal ulcers within 2 months.
Was administered a live vaccine 4 weeks before first dose of study drug.
Any diseases or medical conditions, at the investigator's discretion, that may be unstable or influence their safety or study compliance, including organ transplantation, abuse of psychotropic medication, alcohol abuse or history of drug abuse.
Concurrent participation in another therapeutic clinical study.
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug or their excipients.
Pregnant or breast-feeding patients. Women of childbearing potential will be enrolled only after a confirmed menstrual period. Breast-feeding women can become eligible for this study if she stops breast-feeding, however, cannot restart the breast-feeding on/after the completion of the study treatment.
Male and Female of childbearing potential not using effective contraception during the trial and within 6 months after the end of treatment.

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Interventions

HH3806 is a novel highly potent and selective inhibitor against the BD2 of bromo- and extra-terminal domain (BET ) proteins family (BET-BD2). BET family proteins is known to play important roles in human cancers, associated with tumour cell growth. HH3806 has exhibited strong anti-tumor effects in pre-clinical and animal studies. In this First-In Human study, HH3806 is being studied for the treatment of advanced non-Hodgkin’s lymphomas (NHL), solid tumours and will evaluate the safety and tolerability of HH3806. Approximately 36 participants with either relapsed/ refractory NHL or solid tumours will be enrolled in this study. HH3806 capsule will be administered as an oral capsule once daily for the duration of each 28-day treatment cycle without any study treatment interruption between each cycle. The starting dose level of HH3806 is 10 mg once daily and the decision to dose escalate to the next dose level will be made based on the emerging safety data. Dosing schedule and cycle may be adjusted during the study on the basis of this data. The provisional dose in the dose escalation planned for this study is 10mg, 20mg, 30mg, 40mg, 50mg, 60mg, 75mg, 90mg, 110mg, 135mg and 165mg once daily. The dose level for individual participants will vary depending on the dose level enrolling participants at the time of study entry. HH3806 will be administered at the clinic on days 1, 8, 15 and 22 of cycle 1 & days 1 and 15 of cycle 2. It is to be taken at home on the others days. HH3806 will also be administered at clinic on approx. 3 days before cycle 1 if you are first participant in first 3 dose levels. The participants will complete a dosing diary to record time when HH3806 capsules are taken each day. Intra-patient dose escalation is not permitted at any time within the first four cycles of treatment. After the first four cycles are completed and the participant must have not experienced CTCAE v5.0 grade greater than or equal to 2 HH3806 related toxicity over at least four cycles of therapy at the lower dose, the participant may be considered for treatment at a higher dose of HH3806, which can be only the last cleared dose level of the study drug. The participant who develops any non-DLT during DLT observation period, treatment may be interrupted depending on the grade of AE, but dose modification is not allowed in first cycle. In principle, each participant is only allowed 2 dose reductions. If participant need to modify dose for the third time, the investigator must contact the sponsor to evaluate patient’s benefit and interest, then make the decision together. HH3806 dispensing and administration will also be documented as per study guidelines which will be monitored, and accountability assessed by Sponsor representatives. Study treatment could be continued until disease progression, unacceptable toxicity, death or withdrawal of consent until the date of the last data collection (1 year post-treatment commencement), whichever occurs first. After the completion of the study, if a patient still requires administration of HH3806 which has been assessed as beneficial per the study doctor, the sponsor and the study doctor will discuss the post-study provisions for the patient’s access to HH3806.