A Study to Assess YH002 in Combination With YH001 in Subjects With Advanced Solid Tumors.

• Status: Not yet recruiting
• Trial end date: 2025-01-16
• Target enrollment: 0
• Participant gender: All

Summary

A multicenter, open-label, phase I dose escalation study to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of YH002 in combination with YH001 in subjects with advanced solid tumors

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

Details

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

Criteria

Inclusion Criteria:

To be eligible for study entry patients must satisfy all of the following criteria:

1. Subjects must have the ability to understand and willingness to sign a written informed consent document.

2. Subjects must have histologically advanced or cytologically confirmed solid tumor and and must have at least 1 unidimensional measurable lesion by RECIST 1.1.

3. Subjects have progressed on after treatment with at least one standard therapy, or intolerant of the standard therapy, or no standard therapy accessible to the patients due to any reason.

4. Subjects must be age 18 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. Life expectancy ≥3 months based on investigator's judgement.

7. Subjects must meet the following laboratory values at the screening visit:

• Absolute neutrophil count (ANC) ≥1.5 x 109/L (in absence of growth factor support within 7 days prior to study entry);

• Platelet count ≥100 x 109/L (without colony-stimulating factor or recombinant human thrombopoietin or transfusion support within 7 days prior to study entry);

• Hemoglobin ≥9 g/dL or ≥ 5.6 mmol/L (without growth factor and transfusion support within 7 days prior to study entry);

• Calculated creatinine clearance (CrCL) > 50 mL/min (Cockroft-Gault Equation) or estimated glomerular filtration rate (GFR) > 50 mL/min/1.73m2;

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and alkaline phosphatase (≤3.0 × upper limit of normal (ULN); AST or ALT ≤ 5 × ULN if liver metastases are present;

• Total bilirubin ≤1.5 × ULN, except in subjects with documented Gilbert's Syndrome, who must have a total bilirubin ≤3 × ULN;

• International normalized ratio (INR) ≤ 2.0 and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Exception: INR 2 to ≤ 3 is acceptable for subjects on Warfarin anticoagulation.

8. Women of reproductive potential must have negative serum beta human chorionic gonadotropin (β -HCG) pregnancy test within 7 days of the first dosing. Women of reproductive potential are those who have not been post-menopausal for at least 12 months or who have not undergone bilateral tubal occlusion, hysterectomy, or bilateral salpingectomy.

9. Women of reproductive potential who are sexually active with a non-sterilized male must consistently use highly effective contraception/birth control between signing of the informed consent and 120 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 two or more highly effective methods of contraception/birth control (at least one barrier method) between signing of the informed consent and 120 days after receiving the last administration of the study drug. The Investigator or a designated associate should advise the subject how to achieve effective contraception. Highly effective methods of contraception/birth control are defined as those that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as:

• Barrier methods: male condom plus spermicide, copper T intrauterine device (IUD), levonorgestrel-releasing IUD (e.g. Mirena, is also considered as a hormonal method);

• Hormonal methods: implants, hormone shot or injections, combined pills, mini-pill, and patch. (In case of using oral contraception, women should have been stable on the same pill for a minimum of 3 months before the first dose of study drug).

Exclusion Criteria:

Subjects who meet any of the following criteria cannot be enrolled:

1. Subjects have another active invasive malignancy within 5 years, with the following exceptions and notes:

• History of non-invasive malignancy, such as cervical cancer in situ, non-melanomatous carcinoma of the skin, in situ melanoma, or ductal carcinoma in situ of the breast that is in complete remission years after treatment with curative intent is allowed

2. Current or history of a hematologic malignancy including subjects who have undergone a bone marrow transplant

3. Previous exposure to TNFR such as anti-OX40 antibodies.

4. Subjects must not have received any anticancer therapy or another investigational agent within the shorter of 4 weeks or 5 half-lives before the first dose of the study treatment(subject to the longer one). Except:

• Prior palliative radiotherapy to bone metastases ≤ 2 weeks prior to the first dose of study treatment is acceptable.

• Prior hormonal therapy and herbal therapy approved for anticancer and biologic therapy >2 weeks prior to the first dose of study treatment is acceptable.

5. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to ≤ Grade 1 per CTCAE 5.0, except alopecia ≤ Grade 2.

6. Subjects with a history of ≥ Grade 3 immune-related adverse events resulted from previous immunotherapy.

7. History of clinically significant sensitivity or allergy to monoclonal antibodies and their excipients or known allergies to antibodies produced from Chinese hamster ovary cells, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to YH001 or YH002.

8. Primary central nervous system (CNS) malignancies or symptomatic CNS metastases, except:

• Subjects with asymptomatic CNS metastases might be eligible if the metastasis size ≤1.5 cm and are currently not receiving corticosteroids

• Have no clinical evidence of progression since completion of CNS-directed therapy, minimum 4 weeks between completion of radiotherapy and the first dose and are currently not receiving corticosteroids or Anticonvulsants

9. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease

10. Active, hemodynamically significant pulmonary embolism within 12 weeks prior to the first dose of study drug.

11. Subjects must not have a known or suspected history of an autoimmune disorder, including but not limited to inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of study treatment, except for the following.

• Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders such as vitiligo, or alopecia not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are eligible.

12. Clinically uncontrolled intercurrent illness, including but not limit to an ongoing active infection, active coagulopathy, uncontrolled diabetes (blood glucose > 250 mg/dl), uncontrolled pleural and peritoneal effusion, psychiatric illness that would limit compliance with the study requirements and other serious medical illnesses requiring systemic therapies

13. Severe cardiovascular disease including symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina, uncontrolled hypertension, cardiac arrhythmia, a history of myocardial infarction within 6 months or a history of arterial thromboembolic event and pulmonary embolism within 3 months of the first dose of investigational agent.

14. QTc > 450ms at baseline; no concomitant medications that would prolong the QT interval; no family history of long QT syndrome. Baseline Left ventricular ejection fraction (LVEF) ≤50% measured.

15. Subjects must not have active infection of human immunodeficiency virus, hepatitis B, hepatitis C or Covid-19.

16. Subjects must not have a history of primary immunodeficiency.

17. Subjects from endemic area will be specifically screened for tuberculosis. Subjects with active tuberculosis are excluded. Subjects who have received BCG vaccination may have a false positive PPD test. These subjects are eligible if they have a negative Interferon Gamma Release Assay (IGRA).

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

• Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted. Steroids as anti-emetics for chemotherapy are not allowed.

• Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted.

• Subjects with a condition with anticipated use of systemic steroids above the equivalent of 10 mg prednisone are excluded.

19. Major surgery within 4 weeks prior to study entry and Minor surgery within 2 weeks prior to the first dose.

20. Subjects must not have received a live attenuated vaccine within 28 days before the first dose, and subjects, if enrolled, should not receive live vaccines during the study or for 180 days after the last dose. For inactivated or attenuated COVID -19 vaccine, whether could be injected should follow the local guidance and need sign additional informed consent form about COVID-19 vaccine.

21. Females who are pregnant or lactating or who intend to become pregnant during participation in the study are not eligible to participate.

22. Subjects who are of reproductive potential who refuse to use effective methods of birth control during the course of participation of the study and within 120 days for both women and men of the last dose are ineligible to participate in the study.

23. Any known, documented, or suspected history of illicit substance abuse that would preclude subject from participation, unless clinically justified (i.e., will not interfere with study participation and/or will not compromise trial objectives) per judgment of the Investigator.

24. Any condition that the investigator or primary physician believes may not be appropriate for participating the study.