A Study of onCARlytics (CF33-CD19) in Combination With Blinatumomab in Adults With Advanced or Metastatic Solid Tumors (OASIS)

Study Overview
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Brief Summary
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This is an open-label, dose escalation and dose expansion, multi-center phase I study evaluating the safety and tolerability of CF33-CD19 administered intravenously (IV) or intratumorally (IT) in combination with blinatumomab in adults with advanced or metastatic solid tumors.

Detailed Description
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CF33-CD19, a novel chimeric orthopoxvirus, will be administered as a monotherapy or in combination with blinatumomab to assess the safety and efficacy of the treatment regimens as well as immunological changes in the tumour microenvironment. Subjects eligible for treatment include those with any metastatic or advanced solid tumor who have documented radiological progression per RECIST following at least two prior lines of therapy. All enrolled subjects will be treated with CF33-CD19 on Day 1 and 8 of Cycle 1 and then on Day 1 of each cycle thereafter. Subjects treated with the combination regimen will also receive blinatumomab as a 28-day continuous infusion.

Official Title
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A Phase I, Dose Escalation and Dose Expansion, Safety and Tolerability Study of onCARlytics (CF33-CD19), Administered Intravenously or Intratumorally in Combination With Blinatumomab in Adults With Advanced or Metastatic Solid Tumors (OASIS)

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Biological: CF33-CD19 IT
* Biological: CF33-CD19 IV
* Biological: Blinatumomab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent from subject or legally authorized representative. Age ≥ 18 years old on the date of consent. Life expectancy of at least 3 months. Any histologically or cytologically confirmed advanced or metastatic solid tumor with documented radiological progression per RECIST v1.1 following at least one prior line of treatment. Eligible subjects must have received at least two prior lines of approved therapies, including targeted therapies, for which they are eligible and failed or relapsed on or after that treatment. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1. At least one measurable lesion as defined by RECIST v1.1 criteria. Adequate renal function. Adequate hepatic function. Adequate hematologic function. Willing and able to comply with scheduled visits, study treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Prior treatment with an oncolytic virus or a bispecific CD19-directed CD3 T-cell engager. Continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 4 weeks prior to first dose of study treatment. Any radiation within 2 weeks of start of study treatment. Active autoimmune disease. Current or history of severe skin disease with open wounds. History of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease. History of pancreatitis. > Grade 2 neuropathy. Prior allogeneic tissue/organ transplant or other medical conditions requiring ongoing treatment with immunosuppressive drugs or any condition resulting in a systemic immunosuppressed state. History or presence of brain or other central nervous system (CNS) metastases. History of documented congestive heart failure (New York Heart Association [NYHA] class II - IV), unstable angina, poorly controlled hypertension, clinically significant valvular heart disease or high-risk uncontrolled arrhythmias. Bleeding diathesis due to underlying medical condition or ongoing anticoagulation medication. History or presence of clinically relevant CNS pathology, or any other CNS disability judged by the Investigator to be clinically significant and precluding informed consent or participation in the study. Active infection requiring systemic treatment.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CF33-CD19 IT Administration Monotherapy<br> | Biological: CF33-CD19 IT<br>* Safety Run-In Phase: CF33-CD19 will be administered intratumorally on Days 1 and 8 of each 21-day cycle. Dose Escalation Combination Phase: CF33-CD19 will be administered intratumorally on Days 1 and 8 of Cycle 1 (50-day cycle) and Day 1 of all subsequent 42-day cycles.<br>|
| Experimental: CF33-CD19 IV Administration Monotherapy<br> | Biological: CF33-CD19 IV<br>* Safety Run-In Phase: CF33-CD19 will be administered intravenously on Days 1 and 8 of each 21-day cycle. Dose Escalation Combination Phase: CF33-CD19 will be administered intravenously on Days 1 and 8 of Cycle 1 (50-day cycle) and Day 1 of all subsequent 42-day cycles.<br>|
| Experimental: CF33-CD19 IT Administration in Combination with Blinatumomab<br> | Biological: CF33-CD19 IT<br>* Safety Run-In Phase: CF33-CD19 will be administered intratumorally on Days 1 and 8 of each 21-day cycle. Dose Escalation Combination Phase: CF33-CD19 will be administered intratumorally on Days 1 and 8 of Cycle 1 (50-day cycle) and Day 1 of all subsequent 42-day cycles.<br>Biological: Blinatumomab<br>* Blinatumomab will be infused via a 28-day continuous infusion starting on Day 15 (Cycle 1) and Day 8 (all subsequent cycles).<br>* Other names: Blincyto;|
| Experimental: CF33-CD19 IV Administration in Combination with Blinatumomab<br> | Biological: CF33-CD19 IV<br>* Safety Run-In Phase: CF33-CD19 will be administered intravenously on Days 1 and 8 of each 21-day cycle. Dose Escalation Combination Phase: CF33-CD19 will be administered intravenously on Days 1 and 8 of Cycle 1 (50-day cycle) and Day 1 of all subsequent 42-day cycles.<br>Biological: Blinatumomab<br>* Blinatumomab will be infused via a 28-day continuous infusion starting on Day 15 (Cycle 1) and Day 8 (all subsequent cycles).<br>* Other names: Blincyto;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Treatment Arms - Incidence and severity of Adverse Events | Adverse events will be graded according to CTCAE v5.0. | From first dose of study drug through 30 days following the last dose of study treatment | 
| Monotherapy Treatment Arms - Determination of the Recommended Phase 2 Dose (RP2D) to apply to Dose Escalation Combination Phase as supported by immune response as seen in lymphocyte subsets | Change in lymphocyte subset expression in tumor tissue and peripheral blood pre and post dose | From first dose of study drug through treatment discontinuation, an average of 6 months | 
| Monotherapy Treatment Arms - Determination of RP2D to apply to Dose Escalation Combination Phase as supported by immune response as seen in cytokines | Change in cytokine levels in peripheral blood pre and post dose | From first dose of study drug through treatment discontinuation, an average of 6 months | 
| Monotherapy Treatment Arms - Determination of RP2D to apply to Dose Escalation Combination Phase as supported by anti-tumor activity | Stable Disease and Response (PR and CR) based on RECIST v1.1 and iRECIST v1.0. | From first dose of study drug through treatment discontinuation, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combination Treatment Arms - Determination of the Recommended Phase 2 Dose (RP2D) for CF33-CD19 + blinatumomab combination as supported by immune response as seen in lymphocyte subsets | Change in lymphocyte subset expression in tumor tissue and peripheral blood pre and post dose | From first dose of study drug through treatment discontinuation, an average of 6 months | 
| Combination Treatment Arms - Determination of RP2D for CF33-CD19 + blinatumomab combination as supported by immune response as seen in cytokines | Change in cytokine levels in peripheral blood pre and post dose | From first dose of study drug through treatment discontinuation, an average of 6 months | 
| Combination Treatment Arms - Determination of RP2D for CF33-CD19 + blinatumomab combination as supported by anti-tumor activity | Stable Disease and Response (PR and CR) based on RECIST v1.1 and iRECIST v1.0. | From first dose of study drug through treatment discontinuation, an average of 6 months | 
| All Treatment Arms - Overall Response Rate | Overall Response Rate (ORR) is defined as the proportion of subjects in the efficacy population who achieve a radiographic Investigator-assessed confirmed CR or PR, per RECIST v1.1 or confirmed iCR or iPR per iRECIST v1.0. | From first dose of study drug through treatment discontinuation, an average of 6 months | 
| All Treatment Arms - Progression Free Survival | Progression Free Survival (PFS) defined as the time from first dose of study drug to first documentation of PD based on RECIST 1.1, or to death from any cause. | From first dose of study drug through treatment discontinuation, an average of 6 months | 
| All Treatment Arms - Duration of Response | Duration of Response (DoR) measured as the time from the date a response of PR/iPR or better was first recorded to the date on which progressive disease was first noted or the date of death due to any cause. | From first dose of study drug through treatment discontinuation, an average of 6 months | 
| All Treatment Arms - Disease Control Rate | Disease Control Rate (DCR), measured as the proportion of subjects who achieve an Investigator-assessed confirmed CR/iCR, PR/iPR, or Stable Disease (SD)/immune SD (iSD) per RECIST v1.1 and iRECIST v1.0. | From first dose of study drug through treatment discontinuation, an average of 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Oncolytic Virus, Bispecific T-Cell Engager, BiTE, Blincyto