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Clinical Trial of HG146 Administered to Subjects With Advanced Solid Tumors or Lymphoma

16. september 2026 opdateret af: HitGen Inc.

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

24

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

      • Beijing, Kina
        • National Cancer Center/Cancer Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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):

    1. 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:

  1. Received prior therapies targeting HDAC.
  2. Symptomatic central nervous system (CNS) metastases that have required steroids within 4 weeks prior to first dose of study treatment.
  3. History of intolerant of anti-PD-(L)1 toxicity(Ib).
  4. A condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of enrollment.
  5. Major surgery or major injury <=28 days before the first dose of study treatment,or anticipated major surgery during the study.
  6. Received other anticaner therapies within 4 weeks prior to first dose of study treatment or 5 half life period of anticancer drug .
  7. Active infection requiring systemic treatment.
  8. Prior allogeneic bone marrow transplantation or other solid organ transplantation ( Ib)
  9. Active autoimmune disease or disease of impaired immune system(Ib).
  10. History of Adrenal insufficiency.(Ib)
  11. History orConcurrent condition of other malignant tumors.
  12. 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.
  13. History of severe lung disease.
  14. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.

Andre navne:
  • HG146 capsule
Eksperimentel: 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.

Andre navne:
  • HG146 capsule

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.

Andre navne:
  • PD-1 antistof
Eksperimentel: 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.

Andre navne:
  • HG146 capsule

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.

Andre navne:
  • PD-1 antistof
Eksperimentel: 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.

Andre navne:
  • HG146 capsule

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.

Andre navne:
  • PD-1 antistof

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Part I:Dose-Limiting Toxicities (DLTs)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Part 1:Area under the concentration versus time curve (AUC) of HG146
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: Up to 2 years

OS will be assessed by the investigators

Up to 2 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Efterforskere

  • Ledende efterforsker: Yuankai Shi, National Cancer Center/Cancer Hospital

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

23. september 2021

Primær færdiggørelse (Faktiske)

13. juni 2024

Studieafslutning (Faktiske)

22. december 2024

Datoer for studieregistrering

Først indsendt

12. juli 2021

Først indsendt, der opfyldte QC-kriterier

23. juli 2021

Først opslået (Faktiske)

26. juli 2021

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

21. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

16. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Andre undersøgelses-id-numre

  • HG146CN102

Plan for individuelle deltagerdata (IPD)

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