Trial summary: This trial is exploring increasing doses of a new cancer drug (YH003) in combination with a targeted therapy with the aim of identifying and evaluating maximum tolerated/recommended dose.
Status: COMPLETED - Not Recruiting
Trial identifier: NCT04481009
Sponsor: Eucure (Beijing) Biopharma Co., Ltd
Phase: II
Diagnosis: Locally advanced (Stage III) unresectable or Metastatic (Stage IV) pancreatic ductal adenocarcinoma
Line of therapy: Second-line +
Treatment: YH003 (recombinant humanized agonistic CD40 IgG2 mAb) in combination with Toripalimab (anti-PD-1 mAb) with or without nab-paclitaxel + gemcitabine
  • Key inclusion criteria
    1. Subjects must have the ability to understand and willingness to sign a written informed consent document.
    2. Part I dose escalation:
    3. Have histologically advanced or cytologically confirmed solid tumor. Have progressed after treatment with at least one standard therapy or be intolerant of the standard therapy.
    4. Part II dose expansion:
      • Cohort 2A: Histologically or cytologically confirmed unresectable or metastatic melanoma that had confirmed progressive disease during treatment with an anti-PD-1/PD-L1 therapy with or without additional CTLA-4 therapy. Subjects with BRAF activating mutation could have also received a BRAF inhibitor and/or MEK inhibitor regimen prior to anti-PD-1/PD-L1 therapy.
      • Cohort 2B, 2C: Subject has a histologically or cytologically documented diagnosis of pancreatic ductal adenocarcinoma with unresectable locally advanced/metastatic disease Cohort 2B: had confirmed progressive disease during treatment with first-line standard of care chemotherapy per local standard.
      • Cohort 2C: Treatment-naïve for unresectable locally advanced/metastatic disease.
    5. Subjects must have measurable disease by RECIST 1.1, with at least 1 unidimensional measurable target lesion per RECIST v1.1 for study Part II expansion cohorts.
    6. Subjects must be 18 years of age or older.
    7. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with a life expectancy of ≥3 months.
    8. Subjects must have adequate organ function.
    9. Women of reproductive potential must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test.
  • Key exclusion criteria
    1. Part II Cohort 2A: History of life-threatening toxicity or treatment discontinuation related to prior anti-PD-1/PD-L1 and with or without CTLA-4 combination treatment for subjects with unresectable/metastatic melanoma.
    2. Subjects must not have another active invasive malignancy.
    3. Previous exposure to TNFR such as anti-CD137, OX40, CD27, and CD357 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.
    5. Subjects with a history of ≥ Grade 3 immune-related adverse events resulting from previous immunotherapy.
    6. 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 YH003 or Toripalimab. Also, history of severe hypersensitivity reaction to Nap-paclitaxel and/or gemcitabine.
    7. Primary central nervous system (CNS) malignancies or symptomatic CNS metastases.
    8. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease.
    9. 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.
    10. Clinically uncontrolled intercurrent illness, including an ongoing or active infection, active coagulopathy, uncontrolled diabetes, psychiatric illness that would limit compliance with the study requirements, and other serious medical illnesses requiring systemic therapies.
    11. 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 the investigational agent.
    12. QTc > 450 ms at baseline; no concomitant medications that would prolong the QT interval; no family history of long QT syndrome.
    13. Subjects must not have active infection of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
    14. Subjects must not have a history of primary immunodeficiency.
    15. Subjects from endemic areas will be specifically screened for tuberculosis. Subjects with active tuberculosis are excluded.
    16. Subjects must not receive concurrent or prior use of an immunosuppressive agent within 4 weeks of the first dose of YH003.
    17. Major surgery within 4 weeks prior to study entry and minor surgery within 2 weeks prior to the first dose of YH003.
    18. Subjects must not have received a live attenuated vaccine within 28 days before the first dose of YH003, and subjects, if enrolled, should not receive live vaccines during the study or for 180 days after the last dose of YH003.

YH003004

Locations: Epworth Richmond, Epworth Freemasons (East Melbourne), Epworth Eastern (Box Hill).

Epworth PI: A/Prof Sumitra Ananda

Jreissati Pancreatic Centre at Epworth 

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