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Tolerability and Safety of HF1K16 Injection in Patients With Refractory Solid Tumors

H

HighField Biopharmaceuticals

Status and phase

Enrolling
Phase 1

Conditions

Solid Tumor, Adult

Treatments

Drug: HF1K16 /Arm 160 mg/m²
Drug: HF1K16 /Arm 120 mg or 180 mg
Drug: HF1K16 /Arm 45 mg/m²
Drug: HF1K16 /Arm 90 mg/m²
Drug: HF1K16 /Arm 120 mg/m²

Study type

Interventional

Funder types

Industry

Identifiers

NCT05388487
HF1K16-101(CN)

Details and patient eligibility

About

HF1K16 is an investigational pegylated liposome formulation of All-Trans Retinoic Acid (ATRA) for the induction of remission in patients with acute promyelocytic leukemia (APL) and for the treatment of solid tumors through targeting myeloid derived suppressor cells (MDSCs).

Full description

Myeloid Derived Suppressor Cells (MDSCs) play important roles in constituting the immune suppressive environment promoting cancer development and progression. While previous studies had shown that all-trans retinoic acid (ATRA) could induce MDSC differentiation and maturation, the very poor solubility and fast metabolism of the drug limited its applications as an immune-modulator for cancer immunotherapy

HF1K16 is an investigational pegylated liposome formulation with great ATRA dose loading capacity and sustained drug release property. In preclinical studies, HF1K16 was shown to be able to remodel the host systemic immune homeostasis as well as modify tumor microenvironment (TME). It promotes MDSCs maturation into DCs and facilitates immune responses against cancer cells.

Enrollment

54 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Willing and able to provide the test of informed consent in writing.

  2. Male or female, age > 18 years and < = 75 years.

  3. The subjects had to be diagnosed by histology and/or cytology with locally advanced or metastatic solid tumor. There is no effective standard of care or the patient is intolerant to the standard therapy.

    Cohort 5: The subjects must be diagnosed with glioma by histology, and the disease has relapsed or progressed after previous treatment, and there is no effective standard treatment or the subject is intolerant to standard treatment.

  4. According to the definition of RECIST 1.1, participants must have at least one measurable lesion.

    Cohort 5: at least one lesion that can be measured in two dimensions is required ( RANO criteria).

  5. Eastern group (ECOG) tumor physical state to 0 or 1. Cohort 5: According to Karnofsky physical fitness score ≥ 60.

  6. Expected lifetime > 12 weeks.

  7. Men or women of childbearing age must agree to adopt effective contraception after signing the informed consent form until 180 days after the end of the study. Premenopausal women or those within 2 years after menopause are included.

Exclusion criteria

  1. Patients received systemic antitumor therapy, including chemotherapy, radiotherapy, biologic therapy, endocrine therapy, or immunotherapy within 3 weeks prior to the first dose, except for the following: Nitrosoureas or mitomycin C within 6 weeks; Oral fluorouracils and small molecule drugs within 2 weeks or within 5 half-life periods of the drug (whichever is longer); Antitumour traditional Chinese medicine within 2 weeks.

  2. Adverse effects of previous anti-tumor therapy have not recovered to CTCAE 5.0 grade rating of ≤ grade 1 (except for toxicity judged by the investigator be of no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, etc.)

  3. Patients received other unlisted clinical trial drugs or treatments within 28 days prior to the first dose.

  4. Taken vitamin A or any vitamin A derivatives within 7 days prior to the first dose.

  5. Past history of deep vein thrombosis or pulmonary embolism.

  6. Evidence that there is poor control of thyroid diseases, or diseases of the retina.

  7. Patients have symptomatic central nervous system (CNS) metastases, meningeal metastases, or a primary CNS tumor that is associated with progressive neurological symptoms. Except that the brain metastases are shown to be stable judged by imaging examination within 4 weeks.

    Cohort 5: The above criteria do not apply to the fifth cohort. The fifth cohort allowed inhaled or topical corticosteroids, or hormone therapy at physiological replacement doses due to adrenal insufficiency; short-term (≤7 days) corticosteroids were allowed for prophylaxis (eg, contrast media allergy) or treatment of non-autoimmune conditions ( For example, delayed-type hypersensitivity reactions caused by exposure to allergens); systemic corticosteroids (≥10 mg/day prednisone, or other equivalent corticosteroids) for 7 consecutive days within 14 days of the first dose are not allowed or Immunosuppressant therapy.

  8. Evidences of serious or uncontrolled systemic disease (for example: instability or decompensated respiratory disease, liver or kidney disease)

  9. Serious liver and kidney function damage;

  10. Has clinical significance of cardiovascular disease;

  11. Have known immune inhibitory disease or human immunodeficiency virus (HIV) infection.

  12. Patients with severe osteoporosis or with bone metastases with serum 25-hydroxyvitamin D assay values less than 50 nmol/L.

  13. Active hepatitis (Hepatitis B: HBsAg-positive and HBV-DNA ≥ 500 cps/mL or 200 IU/mLL; HCV RNA-positive).

  14. Persons with known hypersensitivity to any of the active ingredients or excipients or a history of atopic allergic reactions.

  15. The pregnancy test positive (blood beta human chorionic gonadotropin - HCG [B] test positive) or lactationWomen.

  16. Researchers believe that patients with combined disease may affect the compliance.

  17. Participants not willing to or fail to follow the procedure.

  18. Cohort 5: Brain MRI not available.

  19. Cohort 5: uncontrolled epilepsy.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

54 participants in 5 patient groups

Dose escalation cohort 1: HF1K16 given QOD at 45 mg/m²
Experimental group
Description:
The first dosing group (45 mg/m²) will include a sentinel subject receiving one dose followed by a 7-day safety evaluation interval. Three or more subjects will receive 7 doses of HF1K16 QOD at 45 mg/m2 per cycle of 21 days.
Treatment:
Drug: HF1K16 /Arm 45 mg/m²
Dose escalation cohort 2: Oral ATRA followed by HF1K16 QOD at 90 mg/m²
Experimental group
Description:
The second dosing group will receive oral ATRA at 45mg/m², and three days later HF1K16 QOD at 90 mg/m2 for 7 times per cycle of 21 days.
Treatment:
Drug: HF1K16 /Arm 90 mg/m²
Dose escalation cohort 3: HF1K16 QOD at 120 mg/m²
Experimental group
Description:
The cohort 3 will receive 7 doses of HF1K16 QOD at 120 mg/m² per cycle of 21 days.
Treatment:
Drug: HF1K16 /Arm 120 mg/m²
Dose escalation cohort 4: HF1K16 QOD at 160 mg/m²
Experimental group
Description:
The cohort 4 will receive 7 doses of HF1K16 QOD at 160 mg/m² per cycle of 21 days.
Treatment:
Drug: HF1K16 /Arm 160 mg/m²
Dose escalation cohort 5: HF1K16 QOD at 120mg or180 mg
Experimental group
Description:
The cohort 5 will receive 7 doses of HF1K16 QOD at 120 mg or 180mg per cycle of 21 days.
Treatment:
Drug: HF1K16 /Arm 120 mg or 180 mg

Trial contacts and locations

7

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Central trial contact

Yongfeng Huang; Yuhong Xu

Data sourced from clinicaltrials.gov

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