A Trial of ZL-1201 in Subjects with Advanced Cancer

Overview

About this study

First in Human, Phase I Trial of Anti-CD47 Antibody ZL-1201 in Subjects with Advanced Cancer

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Male or female ≥ 18 years.
  • 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.
  • Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumors and lymphomas that are refractory or intolerant to standard of care therapy, or for which no standard therapy exists. Patients should, in the judgement of the investigator, be deemed not appropriate for any other approved therapy with established benefit for that indication.
  • Evaluable disease per RECIST v1.1 for solid tumors or per Lugano 2014 criteria for lymphoma.
  • ECOG performance status 0 – 1.
  • Life expectancy ≥ 3 months.
  • Adequate hepatic function as evidenced by meeting all the following requirements:
    • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3xULN with documented Gilbert’s syndrome;
    • Aspartate aminotransferase      (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; AST and ALT ≤ 5 × ULN if liver metastases are present..
  • Serum creatinine < 1.5 × ULN OR calculated creatinine clearance (CrCL) > 40 mL/min (Cockroft-Gault Equation).
  • Hematological function defined as:
    • Absolute neutrophil count ≥ 1.5 × 10^9/L without growth factor support in the 2 weeks prior to screening;
    • Platelet count ≥ 100 × 10^9/L without transfusion in the 2 weeks prior to screening;
    • Hemoglobin ≥ 10 g/dL without transfusion in the 2 weeks prior to screening.
  • Prothrombin time, international normalized ratio or activated partial thromboplastin time < 1.5 × ULN.
  • Recovery to Grade 0-1, from adverse events related to prior anticancer therapy except alopecia, ≤ Grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy.
  • Archival tissue will be requested from all subjects enrolled in the dose escalation cohort for biomarker testing. If archival tissue is not available, a fresh biopsy, taken from a readily accessible tumor lesion will be obtained, unless the physician feels that collecting the biopsy would pose an unacceptable risk to the subject. Subjects who cannot provide archival tissue or fresh biopsies may still be eligible for enrollment into the dose escalation cohort. Fresh tumor biopsies collected pre- treatment at baseline and post-treatment at week 8 are highly recommended but are not required in the dose escalation cohort.
  • For Part 3, the pharmacodynamic (PD)/dose expansion cohort, all subjects will be required to provide both pre- and post- treatment biopsies for biomarker analysis as follows:
    • pre- treatment fresh tumor biopsies collected at baseline (during screening); and
    • post-treatment biopsies collected during week. 
  • It is also requested that all patients from the PD cohort provide archival tissues (FFPE blocks or 10 unstained sections) if available for biomarker analysis. End of study biopsies are highly recommended but are not required. Subjects entering Part 3 are required to have a readily accessible tumor lesion.
    • Note: The PD cohort will only include patients enrolled in the US, and Chinese patients will not be included in Part 3 given the extensive nature of exploratory molecular analysis that will be required).

Exclusion Criteria:

  • Brain metastases unless patients who are stable treated and off steroids for at least 2 weeks prior to screening or primary brain tumors.
  • Red blood cells transfusion dependence.
  • History of hemolytic anemia or Evans syndrome in the last 6 months.
  • Positive direct antiglobulin test (DAT).
  • Severe cardiovascular disease, including cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction, or unstable angina within 6 months of screening; NYHA class II-IV heart failure within 6 months of screening; Uncontrolled arrhythmia within 6 months of screening.
  • History of deep vein thrombosis within 3 months or pulmonary embolism within 6 months of screening.
  • Use of anticoagulants or anti-platelet agents (Aspirin ≤ 100 mg daily will be allowed, low molecular weight heparin is also allowed).
  • Active infection requiring intravenous therapy within 2 weeks prior to screening.
  • Subject with known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known active or chronic hepatitis B or C infection.
  • Anticancer therapy or radiation therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to screening; Palliative radiotherapy within 2 weeks prior to screening.
  • Previous exposure to any anti-CD-47 monoclonal antibody or SIRPα antibody.
  • Major surgery within 4 weeks prior to screening; minor surgery within 2 weeks prior to screening.
  • Allergy to study drug or components of its formulation.
  • Pregnant or breast-feeding females.
  • Women of reproductive potential who do not consent to use two highly effective methods of birth control (including one barrier method) during treatment and for an additional 180 days after the last administration of study drug. Women of reproductive potential are those who have:
    • not been post- menopausal for at least 12 months and who do not have an FSH level consistent with post-menopausal status; or
    • who have not undergone tubal occlusion, hysterectomy, or bilateral salpingectomy.
  • Men with a partner of childbearing potential who do not consent to use two highly effective methods of birth control (including one barrier method) during treatment and for an additional 180 days after the last administration of study drug.
  • Any other serious underlying medical (e.g. uncontrolled diabetes mellitus, uncontrolled hypertension, active gastric ulcer, uncontrolled seizures, cerebrovascular incidents, gastrointestinal bleeding, severe signs and symptoms of coagulation and clotting disorders), psychiatric, psychological, familial or geographical condition that, in the judgment of the investigator, may interfere with the planned staging, treatment and follow-up, affect subject compliance or place the subject at high risk from treatment-related complications.
  • Symptomatic intrinsic lung disease (chronic obstructive pulmonary disease, pulmonary fibrosis).

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Alex Adjei, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

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Jacksonville, Fla.

Mayo Clinic principal investigator

Yujie Zhao, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Parminder Singh, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions