Study of YH004 (4-1BB Agonist Antibody) in Advanced Solid Tumors And Relapsed Or Refractory Non-Hodgkin Lymphoma

• Status: Not yet recruiting
• Trial end date: 2026-02-07
• Target enrollment: 0
• Participant gender: All

Summary

This is an multicenter, open-label, dose-escalation study of the study drug YH004 . The study is designed to determine the safety, tolerability, maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of YH004 in subjects with advanced solid tumors and relapsed or refractory Non-Hodgkin lymphoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eucure (Beijing) Biopharma Co., Ltd

Criteria

Inclusion Criteria:

1. Willing and able to provide signed and dated informed consent prior to any study related procedures and willing and able to comply with all study procedures.

2. Patients with histologically or cytologically confirmed advanced solid tumor or relapsed or refractory Non-Hodgkin Lymphoma, which has progressed after treatment with standard therapies or intolerant of standard therapies or have no standard of care. Subjects who refuse or are ineligible for standard therapy will be allowed to enroll, their refusal/ineligibility should be documented in medical records. Patients with Non-Hodgkin's Lymphoma should have received at least two systematic treatments.

3. Subject must have evaluable disease by RECIST 1.1 or per Cheson criteria (Lugano 2014).

4. Subjects must be 18 years to 80 years of age at the time of screening.

5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Have life expectancy of at least 12 weeks based on investigator's judgement.

7. Sufficient organ and bone marrow functions before screening or administration.

8. Women of reproductive potential must have negative serum beta human chorionic gonadotropin (β -HCG) pregnancy test at the time of screening or within 7 days of the first dose of study drug.

9. Women of reproductive potential who are sexually active must consistently use highly effective contraception/birth control (less than 1% per year) between signing of the informed consent and 90 days after the last administration of the study drug. Men whose partner is a woman of reproductive potential, unless with documented vasectomy, must agree to consistently use highly effective contraception/birth control between signing of the informed consent and 140 days after receiving the last administration of the study drug.

Exclusion Criteria:

1. Previous exposure to an anti-CD137 (e.g., utomilumab, urelumab) antibodies.

2. Subjects must not have another active invasive malignancy within 2 years or currently, with the following exceptions:

History of completely cured local low-grade tumor, such as non-melanoma skin cancer, ductal carcinoma in situ of the breast, and cervical cancer in situ, is allowed.

Subject with malignancies diagnosed more than 2 years that is in complete remission for more than 1 year after curative intent is allowed with the approval of the sponsor's medical auditor, under the condition that the investigator believes there is no additional safety risk to enroll.

3. Subjects have received any anticancer therapy or another investigational agent within the longer of 4 weeks or 5 half-lives before the first dose of the study drug.

Subjects have received modern traditional chinese medicine preparations with anti-tumor effect approved by NMPA ≤ 2 weeks prior to first medication.

The washout period of the above drugs may be adjusted with the written approval of the sponsor's medical auditor, if there is no effect on the patient's safety or the scientific of the study.

4. Continuance of toxicities due to prior anti-tumor therapy that have not recovered to ≤ Grade 1 per CTCAE 5.0. Unless the investigator confirms that AE has no significant clinical significance or will remains stable under supportive treatment with no potential risk to patient's safety.

5. Subjects who have thoracotomy, laparotomy, craniotomy and other major operations requiring general anesthesia or epidural anesthesia (excluding vascular access establishment) within 4 weeks before the first dose of the study drug, or minor surgery within 2 weeks prior to the first dose, or local puncture anesthesia biopsy within 1 week prior to the first dose, or still have clinically significant complications due to previous surgery do not meet the eligibility criteria.

6. Subjects have received any radiotherapy within the longer of 4 weeks before the first dose of the study drug. Prior palliative radiotherapy to bone metastases ≤ 2 weeks prior to the first dose of study treatment is acceptable. Subjects who still have clinically significant complications due to previous radiotherapy do not meet the eligibility criteria.

7. Subjects with a history of ≥ Grade 3 immune-related adverse events resulted from previous immunotherapy or treatment discontinuation due to previous immunotherapy. Except hypothyroidism, type 1 diabetes and dermatitis (excluding Steven Johnson syndrome and toxic epidermal necrolysis), or ≥ Grade 2 autoimmune myocarditis during previous immunotherapy.

8. Subjects must not receive concurrent or prior use of an immunosuppressive agent within 4 weeks of the first dose of study drug, with the following exceptions and notes:

Under the condition of no active autoimmune disease, patients are allowed to use inhaled or topical cocorticoids.

Other cocorticoids with an equivalent dose of ≤ 10 mg/day prednisone or non autoimmune diseases treatment (such as the treatment for delayed allergy caused by contact with allergens) are permitted.

9. Subjects must not receive any other investigational drug or participated in other clinical studies within 4 weeks before the first dose of study drug.

10. Subjects must not have received a live vaccine or attenuated live vaccine within 4 weeks before the first dose of investigational agent.

11. Known allergies to the active ingredient or excipients of the test drug, or history of severe allergic reaction (≥ grade 3) to any other monoclonal antibody or intravenous therapeutic protein preparation drug.

12. History of interstitial lung disease or noninfectious pneumonia requiring corticosteroid treatment (except for those caused by radiation therapy), current interstitial pneumonitis or non-infectious pneumonitis, history of other serious lung disease or pulmonary embolism within 12 weeks before the first dose.

13. More than moderate amount of uncontrollable pleural, abdominal or pericardial effusion requiring repeated drainage or with obvious symptoms.

14. Subjects must not have an active autoimmune disease, a history of autoimmune disease requiring systemic therapy, or a history of autoimmune disease within 2 years of the first dose of study drug, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory intestinal diseases, Hashimoto's thyroiditis, etc.

15. Clinically uncontrolled illness, including but not limited to severe diabetes, uncontrolled hypertension, a history of critical hypertension or hypertensive encephalopathy, serious endocrine disorders or other serious diseases requiring systemic treatment such as severe abnormal thyroid function.

16. Subjects must not have a history or persistent active virus or tuberculosis infection. Including but not limited to: human immunodeficiency virus antibody (HIVAb) positive, active syphilis, hepatitis C antibody (HCV-Ab) positive and HCV-RNA > the upper limit of the normal value of the detection unit, hepatitis B surface antigen (HBsAg) positive and HBV-DNA copy number > the upper limit of the normal value of the detection unit; active COVID-19 infection at present; active pulmonary tuberculosis, pulmonary tuberculosis history and other active infectious diseases.

17. Severe infections requiring intravenous administration within 7 days before the first dose of study drug.

18. Severe cerebro-cardiovascular disease within 6 months of the first dose of study drug.

19. QTc > 480 ms at baseline, corrected for heart rate using Frederica's formula.

20. Subjects must not have prior organ transplantation including prior allogeneic hematopoietic stem cell transplant.

21. Any known mental illness or disorder, substance abuse history, drug abuse history or alcohol dependence history that would preclude subject from participation.

22. Females who are lactating, except for whom agreed to stop lactating during the trial.

23. Any condition that the investigator believes may not be appropriate for participating the study.