A Study of HG381 Administered to Patients With Advanced Solid Tumors

NCT ID: NCT04998422

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-18
• Study Completion Date: 2025-12-31

Brief Summary

This is a Phase I, first in human, open-label, non-randomized, multicenter study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, preliminary efficacy and establish a recommended dose of HG381 administered intravenously (IV) alone in subjects with advanced solid tumors.

Detailed Description

The trial consists of a dose escalation phase and a cohort expansion phase.In dose escalation phase, escalating doses of HG381 will be evaluated as guided by the traditional 3+3 design . In cohort expansion phase, subjects will receive HG381 alone at a single dose level determined based on the data form dose escalation phase. In total, approximately 57 subjects will participate in the study, approximately 42 in the dose-escalation cohort, and approximately 15 in the expansion cohort.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: HG381 Monotherapy Dose Escalation Cohort

Subjects will receive HG381 IV at every one week intervals (Q1W). Escalating doses of HG381 will be evaluated by the traditional 3+3 design.

Group Type: EXPERIMENTAL

HG381

Intervention Type: DRUG

HG381 is available as white to off-white cake or powder for solution for injection at a unit dose strength of 5 mg per vial. HG381 will be administered as IV injection.

Part B: HG381 Monotherapy Dose Expansion Cohort

Subjects will be administered the recommended Phase 2 dose of HG381 IV Q1W established in Part A of the study.

Group Type: EXPERIMENTAL

HG381

Intervention Type: DRUG

HG381 is available as white to off-white cake or powder for solution for injection at a unit dose strength of 5 mg per vial. HG381 will be administered as IV injection.

Interventions

HG381

HG381 is available as white to off-white cake or powder for solution for injection at a unit dose strength of 5 mg per vial. HG381 will be administered as IV injection.

Intervention Type: DRUG

Other Intervention Names

HG381 for Injection

Eligibility Criteria

Inclusion Criteria

• Capable of giving signed informed consent.
• Life expectancy of at least 3 months.
• Histological or cytological documentation of an advanced solid tumor，subjects with advanced/recurrent solid tumors, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established.
• Measurable disease per RECIST version 1.1, there is at least one measurable lesion during the screening period.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Adequate organ function : Hematologic system: Hemoglobin ≥9 g/dL, Absolute neutrophil count [ANC] ≥1.5x10^9/L, Platelets ≥100x10^9/L, INR ≤ 1.5 and APTT ≤1.5 x ULN; Hepatic system: Total bilirubin ≤1.5 x ULN, ALT and AST ≤ 2.5 x ULN; Renal system: serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min (calculated by the Cockcroft-Gault formula); Cardiac system: left ventricular ejection fraction (LVEF) ≥50% ; QT interval (QTcF) ≤470 ms for women, and ≤450 ms for men; Endocrine system: Thyroid-stimulating hormone (TSH) is within the normal limits.
• Subjects with fertility must agree to take medically approved effective contraceptive measures during the entire trial period and at least 3 months after the last medication.

Exclusion Criteria

• Chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy and other anticancer therapy within 4 weeks.
• Concurrent medical condition requiring the use of other systemic immunosuppressive treatment within 4 weeks before the first dose of study treatment.
• Receipt of any live vaccine within 4 weeks of the start of study treatment.
• Receipt of unmarketed clinical trial drugs or treatments within 4 weeks of the start of study treatment.
• Receipt of surgery or interventional treatment (excluding tumor biopsy, puncture, etc.) within 4 weeks of the start of study treatment.
• History or evidence of cardiovascular and cerebrovascular diseases risk.
• Subjects with uncontrolled diabetes.
• Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within 2 weeks prior to first dose of study treatment.
• Currently or in the past suffering from malignant tumors.
• Uncontrollable pleural effusion, pericardial effusion or ascites still need to be drained frequently after appropriate intervention.
• Active or suspected autoimmune disease.
• History of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis.
• Toxicity from previous treatment including: Toxicity Grade ≥3 related to prior immunotherapy and that led to study treatment discontinuation; Toxicity related to prior treatment that has not resolved to Grade ≤ 1.
• Subjects who have acute bacterial, viral or fungal infections and require systemic anti-infective treatment.
• Positive test for syphilis antibodies or human immunodeficiency virus (HIV) antibodies.
• Subjects who are allergic to test drugs and excipients.
• Women who are pregnant or breastfeeding.
• Known drug or alcohol abuse.
• Patients with mental or neurological diseases.
• Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
• Subjects who have a history of serious systemic disease or any other reason are not suitable to participate in this trial as judged by the investigator.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

HitGen Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianming Xu, M.D

Role: PRINCIPAL_INVESTIGATOR

Chinese PLA General Hospital

Locations

HitGen Inc.

Chengdu, Sichuan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jie Shen, M.S

Role: CONTACT

jie.shen@hitgen.com

+86 2885197385 ext. 8211

Can Xu, B.S

Role: CONTACT

can.xu@hitgen.com

+86 1050953148

Facility Contacts

Jie Shen, M.S

Role: primary

jie.shen@hitgen.com

+86 2885197385 ext. 8211

Yumei Che, M.S

Role: backup

yumei.che@hitgen.com

+86 2885197385

References

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

Reference Type: BACKGROUND

PMID: 30207593 (View on PubMed)

Zhu Y, An X, Zhang X, Qiao Y, Zheng T, Li X. STING: a master regulator in the cancer-immunity cycle. Mol Cancer. 2019 Nov 4;18(1):152. doi: 10.1186/s12943-019-1087-y.

Reference Type: BACKGROUND

PMID: 31679519 (View on PubMed)

Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, Du F, Ren J, Wu YT, Grishin NV, Chen ZJ. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science. 2015 Mar 13;347(6227):aaa2630. doi: 10.1126/science.aaa2630. Epub 2015 Jan 29.

Reference Type: BACKGROUND

PMID: 25636800 (View on PubMed)

Barber GN. STING: infection, inflammation and cancer. Nat Rev Immunol. 2015 Dec;15(12):760-70. doi: 10.1038/nri3921.

Reference Type: BACKGROUND

PMID: 26603901 (View on PubMed)

Abe T, Barber GN. Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-kappaB activation through TBK1. J Virol. 2014 May;88(10):5328-41. doi: 10.1128/JVI.00037-14. Epub 2014 Mar 5.

Reference Type: BACKGROUND

PMID: 24600004 (View on PubMed)

Ramanjulu JM, Pesiridis GS, Yang J, Concha N, Singhaus R, Zhang SY, Tran JL, Moore P, Lehmann S, Eberl HC, Muelbaier M, Schneck JL, Clemens J, Adam M, Mehlmann J, Romano J, Morales A, Kang J, Leister L, Graybill TL, Charnley AK, Ye G, Nevins N, Behnia K, Wolf AI, Kasparcova V, Nurse K, Wang L, Puhl AC, Li Y, Klein M, Hopson CB, Guss J, Bantscheff M, Bergamini G, Reilly MA, Lian Y, Duffy KJ, Adams J, Foley KP, Gough PJ, Marquis RW, Smothers J, Hoos A, Bertin J. Design of amidobenzimidazole STING receptor agonists with systemic activity. Nature. 2018 Dec;564(7736):439-443. doi: 10.1038/s41586-018-0705-y. Epub 2018 Nov 7.

Reference Type: BACKGROUND

PMID: 30405246 (View on PubMed)

Sivick KE, Desbien AL, Glickman LH, Reiner GL, Corrales L, Surh NH, Hudson TE, Vu UT, Francica BJ, Banda T, Katibah GE, Kanne DB, Leong JJ, Metchette K, Bruml JR, Ndubaku CO, McKenna JM, Feng Y, Zheng L, Bender SL, Cho CY, Leong ML, van Elsas A, Dubensky TW Jr, McWhirter SM. Magnitude of Therapeutic STING Activation Determines CD8+ T Cell-Mediated Anti-tumor Immunity. Cell Rep. 2019 Oct 15;29(3):785-789. doi: 10.1016/j.celrep.2019.09.089. No abstract available.

Reference Type: BACKGROUND

PMID: 31618645 (View on PubMed)

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

Reference Type: BACKGROUND

PMID: 19097774 (View on PubMed)

Other Identifiers

HG381CN101

Identifier Type: -

Identifier Source: org_study_id