A Study of HG381 Administered to Patients With Advanced Solid Tumors

NCT04998422 | Recruiting Phase 1

• 1 other identifier: HG381CN101
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Number of subjects achieving Dose-limiting toxicity (DLT)

  DLT is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 and is at least possibly related to study drug.

  Up to Day 21

• Maximum Tolerated Dose (MTD)

  The maximum tolerated dose (MTD) is defined as the maximum dose where the number of cases of DLT ≤ 1/6 of the total number of cases during the DLT observation period. At least 6 evaluable subjects are required to determine MTD.

  Up to 12 months

• Number of subjects with adverse events (AEs) and serious adverse events (SAEs)

  An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or requires medical judgement.

  Up to 24 months

• Severity of AEs

  The severity of AEs will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.

  Up to 24 months

Secondary Outcomes (6)

• Recommended Phase 2 Dose (RP2D) of HG381

  Up to 12 months

• Best objective response based on RECIST 1.1

  Up to 24 months

• HG381 concentrations in plasma following administration of HG381 alone

  Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days)

• Maximum observed concentration (Cmax) following administration of HG381 alone

  Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days)

• Area under the concentration-time curve (AUC) following administration of HG381 alone

  Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days)

Study Arms (2)

Part A: HG381 Monotherapy Dose Escalation Cohort

EXPERIMENTAL

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

Drug: HG381

Part B: HG381 Monotherapy Dose Expansion Cohort

EXPERIMENTAL

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

Drug: HG381

Interventions

HG381 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.

Also known as: HG381 for Injection

Part A: HG381 Monotherapy Dose Escalation Cohort; Part B: HG381 Monotherapy Dose Expansion Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• HitGen Inc.: lead

Study Sites (1)

HitGen Inc.

Chengdu, Sichuan, 610200, China

RECRUITING

Related Publications (8)

• 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.

  PMID: 30207593 BACKGROUND

• 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.

  PMID: 31679519 BACKGROUND

• 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.

  PMID: 25636800 BACKGROUND

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

  PMID: 26603901 BACKGROUND

• 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.

  PMID: 24600004 BACKGROUND

• 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. Erratum In: Nature. 2019 Jun;570(7761):E53. doi: 10.1038/s41586-019-1265-5.

  PMID: 30405246 BACKGROUND

• 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.

  PMID: 31618645 BACKGROUND

• 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.

  PMID: 19097774 BACKGROUND

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Jianming Xu, M.D

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jie Shen, M.S

CONTACT

+86 2885197385; jie.shen@hitgen.com

Can Xu, B.S

CONTACT

+86 1050953148; can.xu@hitgen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 10, 2021
• Study Start: October 18, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)