CF33-CD19 + Blinatumomab for Solid Cancers

(OASIS Trial)

Recruiting at 6 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Imugene Limited

Must not be taking: Corticosteroids, Immunosuppressants, Anticoagulants, others

Disqualifiers: Autoimmune disease, Pneumonitis, CNS metastases, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a new virus and an immune-boosting drug in adults with advanced cancers that haven't responded to other treatments. The virus aims to kill cancer cells directly, while the drug helps the immune system attack the cancer.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on continuous systemic corticosteroids or other immunosuppressive medications within 4 weeks before starting the study treatment.

What data supports the effectiveness of the treatment CF33-CD19 + Blinatumomab for solid cancers?

Blinatumomab has shown effectiveness in treating certain blood cancers by engaging the body's immune cells to target and destroy cancer cells, which suggests it might help in other types of cancer as well. ^{1 2 3 4 5}

What is known about the safety of Blinatumomab (Blincyto) in humans?

Blinatumomab has been shown to be generally safe in humans, but it can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurological issues (such as seizures) in some patients, especially children with certain blood cancers. ^{1 3 6 7 8}

What makes the CF33-CD19 + Blinatumomab treatment unique for solid cancers?

This treatment is unique because it combines CF33-CD19, a novel oncolytic virus, with Blinatumomab, a bispecific T-cell engager (BiTE) that targets CD19 on cancer cells and CD3 on T-cells, to enhance the immune system's ability to attack solid tumors, a mechanism not typically used in standard treatments for solid cancers. ^{1 3 9 10 11}

Eligibility Criteria

Adults over 18 with advanced or metastatic solid tumors that have worsened after at least one treatment line, including targeted therapies. Participants must be in good physical condition (ECOG 0-1), have a measurable lesion, proper organ function, and a life expectancy of over 3 months. Excluded are those on high-dose steroids or immunosuppressants, recent radiation therapy recipients, certain heart conditions, active infections or autoimmune diseases, severe skin disease with open wounds, lung issues requiring steroids, history of pancreatitis or significant neuropathy.

Inclusion Criteria

My advanced cancer has worsened after treatment, and I've had at least two prior treatments.

Written informed consent from subject or legally authorized representative

I am fully active or can carry out light work.

Exclusion Criteria

I haven't taken high-dose steroids or immunosuppressants in the last 4 weeks.

I have or had lung inflammation that needed steroids.

I have had pancreatitis before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CF33-CD19 monotherapy or in combination with blinatumomab. Monotherapy subjects are treated on Day 1 and 8 of Cycle 1 and then on Day 1 of each 21-day cycle. Combination regimen subjects receive CF33-CD19 on Days 1 and 15 of each 28-day cycle, with blinatumomab as a 7-day continuous infusion from Days 2-9 and Days 16-23.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and response rates.

4 weeks

Treatment Details

Interventions

• Blinatumomab (Monoclonal Antibodies)
• CF33-CD19 (CAR T-cell Therapy)

Trial Overview The trial is testing the safety and effectiveness of CF33-CD19 given through IV or directly into the tumor combined with blinatumomab for treating solid tumors. It's an early-phase study where doses will gradually increase to find the safest amount that can be given.

Participant Groups

Group I: CF33-CD19 IV Administration in Combination with Blinatumomab Experimental Treatment 2 Interventions

Group II: CF33-CD19 IV Administration Monotherapy Experimental Treatment 1 Intervention

Group III: CF33-CD19 IT Administration in Combination with Blinatumomab Experimental Treatment 2 Interventions

Group IV: CF33-CD19 IT Administration Monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Imugene Limited

Lead Sponsor

Trials

7

Recruited

340+

Findings from Research

In a pooled analysis of 259 patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia, blinatumomab therapy resulted in a median overall survival of 7.5 months, with a 3-year survival rate of 17.7%.

Patients who achieved a complete remission with blinatumomab and subsequently underwent allogeneic stem cell transplantation had a significantly improved median overall survival of 18.1 months, indicating that long-term survival is possible with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab. Topp, MS., Gökbuget, N., Zugmaier, G., et al.[2021]

Patients who did not respond to blinatumomab treatment showed poorer responses to CD19-CAR T-cell therapy compared to those who responded to blinatumomab or those who had never received it.

This suggests that prior treatment with blinatumomab may negatively impact the effectiveness of subsequent CD19-CAR therapy in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab Nonresponse Is Associated with Poor CD19-CAR Outcome in B-ALL. [2022]

Blinatumomab is a first-in-class immunotherapy that effectively treats B-cell malignancies by engaging the patient's T cells to target CD19-expressing tumor cells, showing significant efficacy in relapsed B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin's Lymphoma.

Clinical trials have demonstrated its effectiveness even in patients who are resistant to chemotherapy, highlighting its potential as a vital treatment option in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab, a bispecific B-cell and T-cell engaging antibody, in the treatment of B-cell malignancies. Burt, R., Warcel, D., Fielding, AK.[2020]

Blinatumomab, a bispecific antibody targeting CD19 and CD3, shows promise in treating B-cell non-Hodgkin's lymphoma and B-precursor acute lymphocytic leukemia, with high response rates observed in early clinical trials.

The treatment effectively redirects T cells to eliminate malignant cells, leading to durable remissions, which is a significant advancement given the limitations of current therapies for advanced malignant diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Nagorsen, D., Baeuerle, PA.[2020]

In a study of 23 adults with B-cell acute lymphoblastic leukemia treated with blinatumomab, pre-emptive intravenous immune globulin (IVIG) did not reduce the incidence of hypogammaglobulinemia or associated infections compared to a control group.

Both groups experienced similar rates of infections and immunoglobulin levels, indicating that IVIG repletion may not be effective in mitigating the risks associated with blinatumomab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. Wo, S., Levavi, H., Mascarenhas, J., et al.[2022]

Blinatumomab is an effective treatment for CD19 expressing B-cell malignancies, showing positive results in both adult and pediatric patients with relapsed B-ALL and those with residual disease after chemotherapy.

The safety profile of blinatumomab is favorable, suggesting it could be a viable alternative to more toxic chemotherapy options, although further research is needed to clarify its role in upfront treatment and in combination with other therapies like CAR-T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SOHO State of the Art Updates and Next Questions | Optimal Timing of Blinatumomab for the Treatment of B-Acute Lymphoblastic Leukemia. Pinchinat, A., Gupta, S., Cooper, SL., et al.[2023]

Blinatumomab is a safe and effective treatment for children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL), showing a low incidence of severe adverse events (only 1.8% experienced grade 3 or 4 cytokine release syndrome).

The treatment led to a median overall survival of 14.6 months, with significantly better outcomes for patients who achieved a complete response and subsequently underwent allogeneic hematopoietic stem cell transplant, highlighting the importance of MRD response in improving survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis. Locatelli, F., Zugmaier, G., Mergen, N., et al.[2022]

Blinatumomab shows a favorable safety profile in pediatric patients with B-cell acute lymphoblastic leukemia (ALL), associated with a lower risk of serious adverse events, febrile neutropenia, and infections compared to traditional chemotherapy.

While blinatumomab does not significantly increase the risk of cytokine release syndrome or seizures, it is linked to a higher risk of encephalopathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. Marrapodi, MM., Mascolo, A., di Mauro, G., et al.[2022]

In a study of 20 patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) treated with blinatumomab, 20% experienced extramedullary relapse, indicating a significant concern for this type of relapse after treatment.

The median time to extramedullary relapse was 179 days, with relapses occurring in various organs, suggesting that while blinatumomab is effective, there is a need for further research to prevent these relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of relapse patterns in patients with acute lymphoblastic leukemia treated with blinatumomab. Lau, KM., Saunders, IM., Goodman, AM.[2021]

In a phase 1 study involving 76 patients with relapsed/refractory non-Hodgkin lymphoma, blinatumomab effectively depleted B-cells within 48 hours at doses of 5 µg/m2/day or higher, demonstrating a clear relationship between drug exposure and B-cell depletion.

The study found that tumor size reduction was also dependent on blinatumomab exposure, with a predicted 50% reduction at specific drug concentration thresholds, indicating that understanding the pharmacokinetics and pharmacodynamics can help optimize dosing in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Relationship of Blinatumomab in Patients with Non-Hodgkin Lymphoma. Hijazi, Y., Klinger, M., Kratzer, A., et al.[2020]

Blinatumomab, a CD19/CD3 bispecific T-cell engager, was found to have an overall response rate of 69% in patients with relapsed/refractory non-Hodgkin lymphoma, indicating its efficacy as a treatment option.

The maximum tolerated dose (MTD) was established at 60 μg/m²/day, with neurologic events being the primary dose-limiting adverse effect, affecting 22% of patients but with no severe grade 4 or 5 events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study. Goebeler, ME., Knop, S., Viardot, A., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Blinatumomab Nonresponse Is Associated with Poor CD19-CAR Outcome in B-ALL. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Blinatumomab, a bispecific B-cell and T-cell engaging antibody, in the treatment of B-cell malignancies. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. [2020]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

SOHO State of the Art Updates and Next Questions | Optimal Timing of Blinatumomab for the Treatment of B-Acute Lymphoblastic Leukemia. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Characterization of relapse patterns in patients with acute lymphoblastic leukemia treated with blinatumomab. [2021]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Relationship of Blinatumomab in Patients with Non-Hodgkin Lymphoma. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study. [2021]