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

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.