HEC-921 Injection as Monotherapy and in Combination With Antineoplastic Therapies in Patients With Advanced Malignant Solid Tumors

NCT07824934 | Recruiting Phase 1

• 1 other identifier: HEC-921-ST-101
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase I Study of HEC-921 Injection as Monotherapy and in Combination with Other AntineoplasticTherapy in Patients with Advanced Malignant Solid Tumors

Conditions

Advanced Malignant Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity (DLT)

  Proportion of participants with dose limiting toxicities during DLT observation window, to identify monotherapy and combination derive maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D).

  The DLT observation period is 21 days after the first administration of HEC-921

• Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  The severity of adverse events (AEs) will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 6.0.

  From first dose of study drug up to 1-year follow-up

Secondary Outcomes (24)

• Objective Response Rate (ORR)

  From first dose of study drug up to 1-year follow-up

• Disease Control Rate (DCR)

  From first dose of study drug up to 1-year follow-up

• Duration of Response

  From first dose of study drug up to 1-year follow-up

• Progression-Free Survival ( PFS)

  from the first dose administration to the first documented PD or death from any cause (whichever occurs first) , up to 1-year follow-up

• Overall Survival ( OS)

  Time from the first dose administration to death from any cause,up to 1-year follow-up

Study Arms (2)

HEC-921 Monotherapy Study

EXPERIMENTAL

Drug: HEC-921

Combination Therapy Study

EXPERIMENTAL

HEC-921 in combination with capecitabine plus oxaliplatin (CAPOX) and bevacizumab

Drug: HEC-921; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Bevacizumab

Interventions

HEC-921 DRUG

Patients will receive specific dose of HEC-921 via intravenous infusion.

HEC-921 Monotherapy Study

Oxaliplatin DRUG

130 mg/m², administered via intravenous infusion on Day 1

Combination Therapy Study

Capecitabine DRUG

1000 mg/m² per dose, orally twice daily on Days 1-14

Combination Therapy Study

Bevacizumab DRUG

7.5 mg/kg, administered via intravenous infusion on Day 1

Combination Therapy Study

Eligibility Criteria

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

You may qualify if:

• Trial participants aged ≥18 years at the time of signing the informed consent form, either male or female;
• Patients with advanced malignant solid tumors confirmed by histology or cytology, who can provide archived or recently collected tumor tissue sections (recently collected samples are preferred), and meet the following requirements:
• Monotherapy dose escalation and dose expansion phases: Patients with advanced malignant solid tumors who have failed or are intolerant to standard therapy, or for whom no standard therapy exists, and whose tumor tissue is LY6G6D+. During the monotherapy dose escalation phase in the low-dose cohorts , there is no restriction on LY6G6D expression in participants' tumor tissue.
• Combination Therapy Phase: Histologically confirmed unresectable advanced colon adenocarcinoma or rectal adenocarcinoma, with no prior systemic therapy, deemed by the investigator suitable for receiving CAPOX combined with bevacizumab as first-line treatment for advanced disease; tumor tissue LY6G6D+ .
• Eastern Cooperative Oncology Group (ECOG) performance status: 0-1;
• Expected survival time ≥12 weeks;
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1);
• Adequate organ function:
• Female or male trial participants of childbearing potential must agree to have no plans for reproduction and to voluntarily use highly effective contraceptive measures with their partner during the study and for 6 months after the last dose; female trial participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose and must not be breastfeeding;
• The patient voluntarily participates, provides fully informed consent, signs the written informed consent form, and demonstrates good compliance.

You may not qualify if:

• Receipt of the following medications or treatments prior to the first dose:
• Received anti-tumor therapies such as chemotherapy or immunotherapy, or other investigational drugs within 3 weeks prior to the first dose; or received oral fluoropyrimidines, small-molecule targeted drugs, or traditional Chinese medicine with anti-tumor indications within 2 weeks prior to the first dose;
• Received radiotherapy (palliative radiotherapy for local bone/brain lesions is permitted if completed within 2 weeks prior to the first dose), major surgical procedures (not fully recovered from surgery or injury), or any live or attenuated live vaccines within 4 weeks prior to the first dose; or planned to receive live vaccines after enrollment;
• Patients who received systemic treatment with corticosteroids (prednisone \>10 mg/day or equivalent) for more than 1 week or other immunosuppressants within 2 weeks prior to the first dose. Inhaled or topical corticosteroids, or systemic prednisone ≤10 mg/day or equivalent doses of similar drugs, are permitted;
• Presence of active central nervous system metastases. Screening is permitted if the patient previously received radiotherapy or surgery, imaging within 4 weeks prior to the first dose indicates stable brain metastases without progression or new neurological symptoms, and corticosteroid therapy was discontinued at least 2 weeks prior to the first dose. Patients with leptomeningeal metastases or brainstem metastases are excluded regardless of treatment status;
• Occurrence of immune-related adverse events leading to permanent discontinuation during prior treatment with immune checkpoint inhibitors (e.g., anti-PD-(L)1, CTLA-4, LAG-3 inhibitors, etc.);
• Prior receipt of LY6G6D-targeted therapy or 4-1BB (CD137)-related therapy (including CAR-T, monoclonal antibodies, bispecific antibodies, etc.);
• Presence of symptomatic pleural effusion, ascites, or pericardial effusion requiring repeated interventions (e.g., puncture or drainage);
• History of interstitial lung disease or prior non-infectious pneumonia treated with corticosteroids, or evidence of active pneumonia on imaging during the screening period;
• Occurrence of a serious infection (CTCAE v6.0 \> Grade 2) within 4 weeks prior to the first administration of the investigational product, such as severe pneumonia requiring hospitalization, bacteremia, or infectious complications; or occurrence of an active infection requiring intravenous anti-infective treatment or unexplained fever \> 38.5°C within 2 weeks prior to the first administration of the investigational product (trial participants with fever caused by the tumor may be enrolled upon judgment by the investigator);
• Severe cardiovascular or cerebrovascular disease, including but not limited to: myocardial infarction, severe/unstable angina, congestive heart failure (New York Heart Association \[NYHA\] functional class ≥2), clinically significant supraventricular or ventricular arrhythmias requiring pharmacological intervention, aortic aneurysm requiring surgical repair, any arterial thrombotic/embolic event, Grade 3 or higher (CTCAE v6.0) venous thrombotic/embolic event, transient ischemic attack, or cerebrovascular accident occurring within 6 months prior to the first study dose; left ventricular ejection fraction (LVEF) \<50% by echocardiography; corrected QT interval (QTc) \>480 ms (calculated using the Fridericia method; if QTc is abnormal, three consecutive measurements may be taken at 2-minute intervals and averaged);
• Active autoimmune disease requiring systemic treatment (e.g., corticosteroids or immunosuppressive drugs) within 2 years prior to the first dose, including but not limited to: systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, vasculitis, etc. However, screening is permitted for hypothyroidism, adrenal insufficiency, or hypopituitarism controlled solely by hormone replacement therapy; type 1 diabetes mellitus; psoriasis or vitiligo not requiring systemic treatment; and childhood asthma/allergies that have resolved;
• History of another malignant tumor within 5 years prior to the first dose; except for cured localized tumors, including carcinoma in situ of the cervix, basal cell carcinoma of the skin, and carcinoma in situ of the prostate;
• Active tuberculosis; hepatitis B (hepatitis B surface antigen \[HBsAg\] positive and HBV DNA \>1000 copies/mL or 200 IU/mL); or hepatitis C (hepatitis C antibody \[HCVAb\] positive and HCV RNA above the lower limit of detection at the study center);
• History of immunodeficiency, including positive test for human immunodeficiency virus (HIV), or known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; Other severe physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study, affect treatment compliance, or interfere with study results, as determined by the investigator to render the participant unsuitable for this study.

Sponsors & Collaborators

• Sunshine Lake Pharma Co., Ltd.: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, 200032, China

RECRUITING

MeSH Terms

Interventions

Oxaliplatin; Capecitabine; Bevacizumab

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Liu Tianshu, MD

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liu Tianshu, MD

CONTACT

86+13681973996; liu.tianshu@zs-hospital.sh.cn

Study Design

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

Model Details: This study adopts a sequential group design. The monotherapy dose escalation and expansion cohorts will be conducted first, followed by the combination therapy dose escalation and expansion cohorts.

Study Record Dates

• First Submitted: September 5, 2026
• First Posted: September 17, 2026
• Study Start: September 18, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: September 24, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)