Study of CRX100 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This clinical study is an open-label, phase 1, dose-escalation study to determine the safety, tolerability, and pharmacokinetic (PK) properties of CRX100 in adult subjects with advanced solid tumors. Patients will be screened and evaluated to determine whether or not they meet stated inclusion criteria. Enrolled subjects will undergo leukapheresis to enable the ex vivo generation of autologous cytokine induced killer (CIK) cells. Patients with triple-negative breast cancer, colorectal cancer, hepatocellular carcinoma, osteosarcoma, epithelial ovarian cancer, and gastric cancer will be considered.

Official Title
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A Phase 1, Open-Label, Dose-Escalation Study of CRX100 in Patients With Advanced Solid Tumors

Conditions
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Solid Tumor, Adult, Triple Negative Breast Cancer, Colorectal Cancer, Hepatocellular Carcinoma, Osteosarcoma, Epithelial Ovarian Cancer, Gastric Cancer

Intervention / Treatment
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* Biological: CRX100 suspension for infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following criteria to be enrolled in this study: Age ≥18 years at the time of consent. Written informed consent in accordance with national, local, and institutional guidelines obtained prior to any study procedures. Subjects must have histologically-confirmed diagnosis of one of the following tumors: triple negative adenocarcinoma of the breast (human epidermal growth factor receptor 2- estrogen receptor- and progesterone receptor- negative [HER2-/ER-/PR-]), adenocarcinoma of the colon or rectum (CRC), hepatocellular carcinoma (HCC), osteosarcoma, epithelial ovarian cancer, or gastric cancer. Documentation of the diagnosis with the original pathology report, or a recent biopsy, is required. Subjects must have relapsed disease or be refractory or intolerant to standard care, or refusing standard therapies. Subjects must have iRECIST evaluable disease using computed tomography (CT) or magnetic resonance imaging (MRI) with IV contrast , with at least one measurable target lesion. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Subjects must have recovered from the effects of recent surgery, radiation therapy, or chemotherapy. Subjects must be free of active infections requiring treatment doses of antibiotics, antifungals, or antiviral medications. No cellular therapy to be administered for at least 12 weeks prior to apheresis. Adequate hematologic function at the time of screening, defined as: absolute lymphocyte count (ALC) >500 cells/mm3, absolute neutrophil count (ANC) >750 cells/mm3, hemoglobin >8 g/dL, and platelet count >50,000 cells/mm3. Hemoglobin and platelet count thresholds must be achievable without transfusion of red blood cells or platelets. Adequate organ function, defined as: Renal function: serum creatinine <1.5x institutional upper limit of normal (ULN) or calculated creatinine clearance >50 mL/min Adequate hepatic function: total bilirubin ≤1.5x institutional upper limit of normal; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x institutional upper limit of normal, unless liver metastases are present, in which case it must be ≤5x ULN; International Normalized Ratio (INR) ≤1.5. For subjects with HCC, adequate hepatic function is defined as: total bilirubin ≤3x institutional upper limit of normal, AST/ALT ≤5x institutional upper limit of normal, INR ≤1.7, Child-Turcotte-Pugh score <8. Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have negative serum ß-human chorionic gonadotropin (ß-HCG) or urine pregnancy test. Women of childbearing potential must agree to use highly effective methods of contraception throughout the study and for 6 months after the last dose of CRX100. Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method throughout the study and for 6 months after the last dose of CRX100. Subjects must be willing to comply with all study procedures, requirements and follow-up examinations. Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from participation in this study: Subjects with new or progressive brain metastasis. Subjects with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Active or history of autoimmune disease (known or suspected). Exceptions are permitted for vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition requiring only hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger. Have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to apheresis, and within 14 days prior to infusion. Inhaled or topical steroids and adrenal replacement doses (≤10 mg daily prednisone equivalents) are permitted in the absence of active autoimmune disease. Short-term (<48 hr) steroid pretreatment for contrast allergy for imaging is permitted. Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, life-threatening illnesses unrelated to cancer, or any serious medical or psychiatric illness that could, in the Investigator's opinion, interfere with participation in this study. Pregnant or nursing an infant (subject or household contacts). Clinically significant immunodeficiency (e.g., due to underlying illness and/or medication) in a subject or household contacts. Have any underlying medical condition (including, but not limited to, ongoing or active infection requiring treatment, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia), psychiatric condition, or social situation that, in the opinion of the Investigator, would compromise study administration as per protocol or compromise the assessment of AEs. Have a history of another invasive malignancy, except for the following circumstance: individuals with a history of invasive malignancy are eligible if they have been disease free and off treatment for at least 2 years or are deemed by the Investigator to be at low risk for recurrence of that malignancy; individuals with the following cancers are eligible if diagnosed and treated: carcinoma in situ of the breast, oral cavity, or cervix, localized prostate cancer, or basal cell or squamous cell carcinoma of the skin. When enrolling a subject with another malignancy, the Investigator should consider discussing the subject with the Medical Monitor. Treatment with any investigational drug study, oncolytic viral therapy or immunotherapy within three (3) weeks of enrollment. Chemotherapy three (3) weeks prior to infusion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Dose escalation cohort for treatment of solid tumors that are relapsed, refractory or intolerant to standard care, or refusing standard therapies. | Biological: CRX100 suspension for infusion<br>* A fixed dose of CIK cells combined with the specified dose of CDSR.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of treatment-emergent Adverse Events and Dose Limiting Toxicities | The Primary Outcome Measure will be based on the frequency of treatment-emergent Adverse Events and Dose Limiting Toxicities during and after the administration of a single dose of the investigational drug. | 28 days following dose administration for each dosed subject. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biodistribution of CRX100 based on subject's viral load as assessed through a viral shedding assay. | To characterize the biodistribution of CRX100 based on each subject's viral load as assessed through a viral shedding assay, following a single dose of investigational product. | 28 days following dose administration for each dosed subject. | 
| Immune response to investigational drug based on subject's levels of neutralizing antibodies. | Levels of neutralizing vvDD antibodies will be summarized by dose level and time point following a single dose of investigational product. | 28 days following dose administration for each dosed subject. | 
| Early anti-tumor activity of investigational drug based on iRECIST criteria | Summarized based on best response observed using RECIST classification of response. Overall response and frequencies of each level of response. | 6 months after dose administration for each dosed subject. |