Clinical trial NCT06063317: A Study of onCARlytics (CF33-CD19) in Combination With Blinatumomab in Adults With Advanced or Metastatic Solid Tumors (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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor, Adult
Keywords: Immunotherapy
Oncolytic Virus
Bispecific T-Cell Engager
BiTE
Blincyto
Lead sponsor: Imugene Limited
Sponsor class: INDUSTRY
First posted: 2023-10-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 and with or without hydroxyurea in adults with advanced or metastatic solid tumors.

Detailed description: CF33-CD19, a novel chimeric orthopoxvirus, will be administered as a monotherapy or in combination with blinatumomab and with or without hydroxyurea 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.

Eligibility criteria: 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. Prior allogeneic tissue/organ transplant or other medical conditions requiring ongoing treatment with immunosuppressive drugs or any condition resulting in a systemic immunosuppressed state.
9. 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.
10. 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.
11. Bleeding diathesis due to underlying medical condition or ongoing anticoagulation medication.
12. 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.
13. Active infection requiring systemic treatment.

Primary outcomes:
measure: All Treatment Arms - Incidence and severity of Adverse Events
timeFrame: From first dose of study drug through 30 days following the last dose of study treatment
measure: 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
timeFrame: From first dose of study drug through treatment discontinuation, an average of 6 months
measure: Monotherapy Treatment Arms - Determination of RP2D to apply to Dose Escalation Combination Phase as supported by immune response as seen in cytokines
timeFrame: From first dose of study drug through treatment discontinuation, an average of 6 months
measure: Monotherapy Treatment Arms - Determination of RP2D to apply to Dose Escalation Combination Phase as supported by anti-tumor activity
timeFrame: From first dose of study drug through treatment discontinuation, an average of 6 months
Secondary outcomes:
measure: Combination Treatment Arms - Determination of the Recommended Phase 2 Dose (RP2D) for CF33-CD19 + blinatumomab + hydroxyurea combination as supported by immune response as seen in lymphocyte subsets
timeFrame: From first dose of study drug through treatment discontinuation, an average of 6 months
measure: Combination Treatment Arms - Determination of RP2D for CF33-CD19 + blinatumomab + hydroxyurea combination as supported by immune response as seen in cytokines
timeFrame: From first dose of study drug through treatment discontinuation, an average of 6 months
measure: Combination Treatment Arms - Determination of RP2D for CF33-CD19 + blinatumomab + hydroxyurea combination as supported by anti-tumor activity
timeFrame: From first dose of study drug through treatment discontinuation, an average of 6 months
measure: All Treatment Arms - Overall Response Rate
timeFrame: From first dose of study drug through treatment discontinuation, an average of 6 months
measure: All Treatment Arms - Progression Free Survival
timeFrame: From first dose of study drug through treatment discontinuation, an average of 6 months
measure: All Treatment Arms - Duration of Response
timeFrame: From first dose of study drug through treatment discontinuation, an average of 6 months
measure: All Treatment Arms - Disease Control Rate
timeFrame: From first dose of study drug through treatment discontinuation, an average of 6 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern
state: Illinois
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
References: