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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Biological: CF33-CD19 IT; Biological: CF33-CD19 IV; Biological: Blinatumomab

Detailed Description

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 monotherapy subjects will be treated with CF33-CD19 on Day 1 and 8 of Cycle 1 and then on Day 1 of each 21-day cycle thereafter. Subjects treated with the combination regimen will receive CF33-CD19 on Days 1 and 15 of each 28-day cycle. In addition, they will receive blinatumomab as a 7-day continuous infusion from Days 2-9 and Days 16-23 of each cycle.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuni Kim; Phone Number: +61 2 9423 0881; Email: info@imugene.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Contact: Aruna Parikh
      • Principal Investigator: Dan Li, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati
      • Contact: Kayla Webb
      • Principal Investigator: Jennifer Leddon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent from subject or legally authorized representative.
2. Age ≥ 18 years old on the date of consent.
3. Life expectancy of at least 3 months.
4. Any histologically or cytologically confirmed advanced or metastatic solid tumor with documented radiological progression per RECIST v1.1. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
6. At least one measurable lesion as defined by RECIST v1.1 criteria.
7. Adequate renal function.
8. Adequate hepatic function.
9. Adequate hematologic function.
10. Willing and able to comply with scheduled visits, study treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Prior treatment with a poxvirus based oncolytic virus or a bispecific CD19-directed CD3 T-cell engager.
2. 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.
3. Any radiation within 2 weeks of start of study treatment.
4. Active autoimmune disease.
5. Current or history of severe skin disease with open wounds.
6. History of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
7. History of pancreatitis.
8. > Grade 2 neuropathy.
9. Prior allogeneic tissue/organ transplant or other medical conditions requiring ongoing treatment with immunosuppressive drugs or any condition resulting in a systemic immunosuppressed state.
10. Medical history of central nervous system (CNS) metastases unless the subject has completed definitive treatment for the CNS lesions with whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) and are neurologically stable, asymptomatic, and off corticosteroids for at least 2 months prior to first dose.
11. 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.
12. Bleeding diathesis due to underlying medical condition or ongoing anticoagulation medication.
13. 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.
14. Active infection requiring systemic treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CF33-CD19 IT Administration Monotherapy	Biological: CF33-CD19 IT; Safety Run-In Phase: CF33-CD19 will be administered intratumorally on Days 1 and 8 of Cycle 1 and Day 1 of each subsequent 21-day cycle. Dose Escalation Combination Phase: CF33-CD19 will be administered intratumorally on Days 1 and 15 of each 28-day cycle.
Experimental: CF33-CD19 IV Administration Monotherapy	Biological: CF33-CD19 IV; Safety Run-In Phase: CF33-CD19 will be administered intravenously on Days 1 and 8 of Cycle 1 and Day 1 of each subsequent 21-day cycle. Dose Escalation Combination Phase: CF33-CD19 will be administered intravenously on Days 1 and 15 of each 28-day cycle.
Experimental: CF33-CD19 IT Administration in Combination with Blinatumomab	Biological: CF33-CD19 IT; Safety Run-In Phase: CF33-CD19 will be administered intratumorally on Days 1 and 8 of Cycle 1 and Day 1 of each subsequent 21-day cycle. Dose Escalation Combination Phase: CF33-CD19 will be administered intratumorally on Days 1 and 15 of each 28-day cycle.; Biological: Blinatumomab; Blinatumomab will be infused via a 7-day continuous infusion from Days 2-9 and Days 16-23 of each 28-day cycle.; Other Names: Blincyto
Experimental: CF33-CD19 IV Administration in Combination with Blinatumomab	Biological: CF33-CD19 IV; Safety Run-In Phase: CF33-CD19 will be administered intravenously on Days 1 and 8 of Cycle 1 and Day 1 of each subsequent 21-day cycle. Dose Escalation Combination Phase: CF33-CD19 will be administered intravenously on Days 1 and 15 of each 28-day cycle.; Biological: Blinatumomab; Blinatumomab will be infused via a 7-day continuous infusion from Days 2-9 and Days 16-23 of each 28-day cycle.; Other Names: Blincyto

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imugene Limited

Publications and helpful links

Helpful Links

• Imugene Limited (ASX: IMU) is a publicly-listed Australian biotechnology company developing cancer immunotherapies.

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: September 14, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): October 2, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Oncolytic Virus; BiTE; Blincyto; Bispecific T-Cell Engager
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: CF33-CD19-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No