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

Solid Tumor, Adult Clinical Trial

— OASIS  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06063317
• Other study ID #: CF33-CD19-101
• Status: Recruiting
• Phase: Phase 1
• Start date: October 2, 2023
• Est. completion date: September 2025

Study information

• Verified date: April 2024
• Source: Imugene Limited
• Contact: Yuni Kim
• Phone: +61 2 9423 0881
• Email: info[@]imugene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: September 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Adult

Intervention

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.
• 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.
• Blinatumomab
Blinatumomab will be infused via a 7-day continuous infusion from Days 2-9 and Days 16-23 of each 28-day cycle.

Locations

Country	Name	City	State
United States	University of Cincinnati	Cincinnati	Ohio
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Imugene Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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