MC# 22-31 - A Phase I Trial of SIM1811-03 in Subjects with Advanced Solid Tumors and Cutaneous T-cell Lymphoma

  • Agent(s): SIM1811-03
  • Disease Type(s): Solid Tumor, Cutaneous T-cell Lymphoma
  • Phase(s): I
  • Drug Classification(s): Immunotherapy, Monoclonal Antibody, Targeted Therapy
  • Molecular Target(s): TNFR2

Mechanism of Action

SIM1811-03, binds potently and selectively to TNFR2 and induces CD4 and CD8 T cell activation and proliferation. Targeting TNFR2 is anticipated to yield greater anti-tumor immunity by stimulating T-cell activation and proliferation in the tumor microenvironment than targeting other costimulatory receptors.


In this study, the sponsor and investigators want to learn:

  • How much of SIM1811-03 can be given with an acceptable level of side effects
  • The effects of SIM1811-03 (good and bad)
  • How much of SIM1811-03 is absorbed into the blood and how fast it is removed
Inclusion Criteria
  1. Written informed consent must be obtained prior to any procedures that are not considered standard of care
  2. ≥18 years old on the day of signing informed consent, male or female
  3. Histologically and/or cytologically documented advanced/metastatic solid tumors or histologically confirmed CTCL.  Patients with lymphoma other than CTCL are not eligible.
  4. Have relapsed or refractory advanced solid tumors CTCL, whose disease has progressed during or after standard therapy
  5. At least one measurable tumor lesion (RECIST 1.1) for patients with solid tumors.  Tumor lesions previously treated with radiotherapy or local therapy will not be considered as measurable unless progression is documented.
  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  7. Life expectancy of ≥ 12 weeks
  8. Adequate organ and marrow functions as defined in protocol: (blood transfusion, blood component transfusion, or hematopoietic stimulating factors within 14 days prior to the first dose is not allowed)
  9. Provide archival tumor samples or fresh tumor biopsy (mandatory for Phase Ib, and recommended for Phase Ia)
  10. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of the pre-study visit, through the course of the study and for 120 days after the last dose of study medication.  Female patients of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication.  Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity from the time of the pre-study visit, through the course of the study and for 120 days after the last dose of study medication.  Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.  Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.  Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of SIM1811-03 administration.
Exclusion Criteria
  1. Participated in an interventional clinical trial or has used investigational devices within 28 days prior to first dose of study drug or received any following systemic anti-cancer treatments:
    1. cytotoxic chemotherapy, targeted therapy, immune checkpoint inhibitor within 4 weeks (such as PD-1 inhibitor, PD-L1 inhibitor, or CTLA-4 inhibitor);
    2. radiotherapy within 2 weeks (palliative radiotherapy is allowed at least 1 week before the study drug treatment)
  2. Toxicity and side effects (due to previous anticancer treatments) have not recovered to ≤ grade 1, unless such AE is not considered to pose safety risks (such as hair loss and neuropathy ≤ grade 2 caused by chemotherapy)
  3. Required use of corticosteroids for more than 7 consecutive days within 14 days prior to the first dose of study treatment (> 10 mg daily prednisone equivalent for solid tumors; > 20 mg daily prednisone equivalent for CTCL).  Note: Inhaled or local corticosteroids or dose of prednisone or equivalent drugs ≤ 10mg daily prednisone equivalent are permitted, Prophylaxis with short-term (≤ 7 days) use of glucocorticoids is allowed (e.g., for subjects with a history of severe allergy, glucocorticoid prophylaxis may be used by the Investigator according to local practice when alternative anti-allergic drugs cannot be used to prevent contrast allergy) or for the treatment of non-autoimmune diseases (e.g., delayed hypersensitivity reaction due to contact allergens).
  4. Patients with active or history of or risk of autoimmune disease ( e.g., patients with organ transplant using immunosuppressive drug).  However, subjects with type 1 diabetes mellitus, hypothyroidism requiring hormone replacement therapy, skin disease that do not require systemic treatment (vitiligo, psoriasis, or hair loss) may be allowed.  For any uncertainty, it is recommended to consult the sponsor’s medical monitor before signing the informed consent.
  5. Major surgery (except biopsy) or unhealed wound within 4 weeks prior to first dose of study drug
  6. Any other current or previous malignancy within the past 2 years except:
    1. adequately treated basal cell or squamous cell skin cancer
    2. carcinoma in situ of the cervix
    3. carcinoma in situ of the breast
    4. local prostate cancer after radical resection and/ or definitive radiotherapy with stable prostate specific antigen (PSA) levels for 1 years
  7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis, with obvious intracranial hypertension or neuropsychiatric symptoms (Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and neurologically asymptomatic), have no evidence of new or enlarging brain metastases confirmed by repeat imaging, and have not required steroids for at least 14 days before first dose of trial treatment)
  8. History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, symptomatic interstitial lung disease or evidence of active pneumonia that is not considered appropriate by the investigator
  9. Subjects with a history of active pulmonary tuberculosis infection within 1 year, those subjects with history more than 1 year prior to the first dose of study drug maybe considered suitable if there is no evidence of active pulmonary tuberculosis judged by the investigator
  10. History of hemorrhagic disease requiring transfusion within the last 3 months
  11. Known psychiatric disorder or drug abuse that would interfere the trial requirements
  12. Patient is known to be positive for human immunodeficiency virus (HIV) infection or active bacterial or fungal infection requiring systemic treatment 14 days before the first study drug treatment (CTCL subjects with history of HTLV-1 infection should also be excluded)
  13. Active hepatitis B (HBsAg-positive and HBV DNA ≥ ULN) or hepatitis C (HCV antibody positive and HCV RNA ≥ ULN)
  14. Patients with clinically significant cardiovascular diseases, including but not limited to myocardial infarction, severe/unstable angina pectoris, primary cardiomyopathy, cerebrovascular accident (including transient cerebral ischemia, cerebral hemorrhage, cerebral infarction), or congestive heart failure (New York Heart Association class > 2) in the past 6 months; symptomatic coronary heart disease requiring drug treatment; arrhythmia requiring drug treatment; QTcF interval > 480 ms by electrocardiogram; or uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg after adequate drug treatment)
  15. Vaccination with live and attenuated vaccine within 28 days before screening (patients with novel coronavirus vaccines may be enrolled)
  16. History of severe allergic reaction to the study drug or excipients used in the protocol
  17. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-study visit through 120 days after the last dose of trial treatment.  Men and non-pregnant, non-breast-feeding women may be enrolled if they are willing to use 2 methods of birth control or are considered highly unlikely to conceive.  Highly unlikely to conceive is defined as 1) surgically sterilized, or 2) postmenopausal (a woman who is ≥45 years of age and has not had menses for greater than 1 year will be considered postmenopausal), or 3) not heterosexually active for the duration of the study.  The two birth control methods can be barrier method or a barrier method plus a hormonal method to prevent pregnancy. Patients should start using birth control from the time of the pre-study visit, through the course of the study and for 120 days after the last dose of study medication.  The following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner), copper intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a presentational agent (including oral, subcutaneous, intrauterine, or intramuscular agents).
  18. Diagnosis of primary or acquired immunodeficiency disease or any other form of immunosuppressive therapy within 7 days of the first dose of study drug
  19. Has had an allogeneic tissue/solid organ transplant or graft-versus-host disease
  20. Patients who have ascites requiring drainage or diuretic treatment or pleural effusion or pericardial effusion requiring drainage and/or accompanied by shortness of breath within 2 weeks before the first dose of study drug treatment
  21. Other conditions that researchers consider inappropriate for inclusion


  • Dallas, TX - Mary Crowley Cancer Research - Medical City

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Re: MC# 22-31