Clinical Trial of HG146 Administered to Subjects With Advanced Solid Tumors or Lymphoma
A Phase I Open Label Study of HG146 Alone /in Combination With PD-(L)1 Inhibitor Administered With and Without Anticancer Agents in Participants With Advanced Solid Tumors or Lymphoma
This is a Phase I, open-label, repeat-dose, non-randomized, multicenter study to evaluate the safety, tolerability, and preliminary clinical activity and establish a recommended dose of HG146 administered orally (PO) alone (Part 1) or co-administered (Part 2) with PD-（L）1 inhibitor in subjects with refractory/relapsed solid tumors or Lymphoma. Part 1 consists of a dose escalation phae,Part2 consists of a dose escalation phase and a cohort expansion phase. In Part 1, escalating doses of HG146 will be evaluated as guided by the "3+3" approach. In Part 2A, escalating doses of HG146 in combination with PD-(L)1 inhibitor will be evaluated as guided by the "3+3" approach. In Part 2B, subjects will receive a single dose level of HG146 as identified based on data from Part 2, in combination with PD-(L)1 inhibitor . A total of approximately 96 subjects will be enrolled in this study, approximately 36 for dose escalation cohorts, and approximately 60 in the expansion cohorts.
Přehled studie
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
-
-
-
Beijing, Čína
- National Cancer Center/Cancer Hospital
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Key Inclusion Criteria:
1 Subject must be >=18 years of age at the time of signing the informed consent.
2- Ia/Ib dose escalation phase（Part1 and Part 2A）：Subjects with advanced/Metastatic solid tumors or Lymphoma, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established.
-
Ib dose expansion phase（Part 2）:
- Cohort 1,Subjects with advanced/Metastatic solid tumors or Lymphoma, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established, have not been treated with PD-(L)1 antibody； 2）Cohort 2,Subjects with advanced/Metastatic solid tumors or Lymphoma, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established, have progressed on PD-(L)1 antibody； 3 Measurable disease per RECIST version 1.1 or Lugano 2014（If applicable）. 4 Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1. 5 Has adequate organ function. 6 Signed informed consent form (ICF) and able to comply with study requirements.
Key Exclusion Criteria:
- Received prior therapies targeting HDAC.
- Symptomatic central nervous system (CNS) metastases that have required steroids within 4 weeks prior to first dose of study treatment.
- History of intolerant of anti-PD-(L)1 toxicity（Ib）.
- A condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of enrollment.
- Major surgery or major injury <=28 days before the first dose of study treatment,or anticipated major surgery during the study.
- Received other anticaner therapies within 4 weeks prior to first dose of study treatment or 5 half life period of anticancer drug .
- Active infection requiring systemic treatment.
- Prior allogeneic bone marrow transplantation or other solid organ transplantation ( Ib)
- Active autoimmune disease or disease of impaired immune system(Ib).
- History of Adrenal insufficiency.(Ib)
- History orConcurrent condition of other malignant tumors.
- Recent (within the past 6 months) history of Unstable or serious diseases, such as pancreatitis, severe angina, prolonged QT interval, congestive heart failure, myocardial infarction, pulmonary hypertension, stroke, and severe seizures, etc.
- History of severe lung disease.
- Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: Part 1:HG146 Monotherapy, Dose-escalation Cohort
Subjects will receive HG146 PO at every two days intervals (qod) for 14 consecutive days,7 days off, 21 days/ cycle. Escalating doses of HG146 will be evaluated using 3+3 approach. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
Ostatní jména:
|
|
Experimentální: Part 2A:HG146 + PD-(L)1 antibody, Dose escalation Cohort
Subjects will receive HG146 PO at every two days intervals (qod) for 14 consecutive days,7 days off, along with PD-(L)1 antibody IV once every 3 weeks (Q3W),21 days/ cycle. Escalating doses of HG146 in combination with PD-(L)1 antibody will be evaluated. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
Ostatní jména:
PD-(L)1 Antibody is available as solution for infusion or lyophilized powder for reconstitution to be administered Q3W. It will be administered as an IV infusion for 30 minutes.
Ostatní jména:
|
|
Experimentální: Part 2B-1：HG146 combination Expansion Cohort 1
Subjects who have not been treated with PD-(L)1 antibody，will receive HG146 po for 14 consecutive days,7 days off, in combination with PD-(L)1 antibody IV Q3W. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
Ostatní jména:
PD-(L)1 Antibody is available as solution for infusion or lyophilized powder for reconstitution to be administered Q3W. It will be administered as an IV infusion for 30 minutes.
Ostatní jména:
|
|
Experimentální: Part 2B-2：HG146 combination Expansion Cohort 2
Subjects who have progressed on PD-(L)1 antibody, will receive HG146 po for 14 consecutive days,7 days off, in combination with PD-(L)1 antibody IV Q3W. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
Ostatní jména:
PD-(L)1 Antibody is available as solution for infusion or lyophilized powder for reconstitution to be administered Q3W. It will be administered as an IV infusion for 30 minutes.
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Part I：Dose-Limiting Toxicities (DLTs)
Časové okno: Up to 26 Days in Cycle 0 and Cycle 1
|
Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0) |
Up to 26 Days in Cycle 0 and Cycle 1
|
|
Part I：Serious Adverse Events (SAEs) and Adverse Events (AE)
Časové okno: Up to 2 years
|
Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE) According to Safety performance. |
Up to 2 years
|
|
Part I：Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146
Časové okno: Up to 2 years
|
Maximum tolerated dose or Recommended Phase II dose of HG146 will be decided according to safety and effective results. |
Up to 2 years
|
|
Part 2A: Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0)
Časové okno: Up to 21 Days in Cycle 1
|
Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0) |
Up to 21 Days in Cycle 1
|
|
Part 2A: Serious Adverse Events (SAEs) and Adverse Events (AE)
Časové okno: Up to 2 years
|
Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE) According to Safety performance. |
Up to 2 years
|
|
Part 2A:Maximum tolerated dose or Recommended Phase II dose (RP2D) of HG146 in combination with PD-(L)1 antibody
Časové okno: Up to 2 years
|
Maximum tolerated dose or Recommended Phase II dose of HG146 will be decided according to safety and effective results. |
Up to 2 years
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Part 1:Area under the concentration versus time curve (AUC) of HG146
Časové okno: At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
|
|
Part 1:Peak plasma concentration (Cmax) of HG146
Časové okno: At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
|
|
Part 1:Time of Cmax (Tmax) of HG146
Časové okno: At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15(Except for cycle 0, each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15(Except for cycle 0, each cycle is 21 days)
|
|
Part 1:Apparent terminal half-life (T1/2) of HG146
Časové okno: At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
|
|
Part1: objective response rate (ORR)
Časové okno: Up to 2 years
|
ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Part1: Best overall response (BOR)
Časové okno: Up to 2 years
|
BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Part1: Duration of response (DOR)
Časové okno: Up to 2 years
|
DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Part 1:Time-to-response (TTR)
Časové okno: Up to 2 years
|
TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Part 1:Progression-Free Survival (PFS)
Časové okno: Up to 2 years
|
PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Part 2:Area under the concentration versus time curve (AUC) of HG146
Časové okno: At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
|
Part 2:maximum observed plasma concentration (Cmax) of HG146
Časové okno: At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
|
Part 2:time of maximum observed plasma concentration (Tmax) of HG146
Časové okno: At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
|
Part 2:apparent terminal half-life (T1/2) of HG146
Časové okno: At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
|
Part2: objective response rate (ORR)
Časové okno: Up to 2 years
|
ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Part2: Best overall response (BOR)
Časové okno: Up to 2 years
|
BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Part2: Duration of response (DOR)
Časové okno: Up to 2 years
|
DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Part 2:Time-to-response (TTR)
Časové okno: Up to 2 years
|
TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Part 2:Progression-Free Survival (PFS)
Časové okno: Up to 2 years
|
PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Overall survival (OS)
Časové okno: Up to 2 years
|
OS will be assessed by the investigators |
Up to 2 years
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Yuankai Shi, National Cancer Center/Cancer Hospital
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- HG146CN102
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .