CF33-CD19 + Blinatumomab for Solid Cancers

(OASIS Trial)

Recruiting at 7 trial locations

Overseen By Yuni Kim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Imugene Limited

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

Disqualifiers: Autoimmune disease, Pneumonitis, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals with advanced solid tumors that have worsened after at least two other treatments. It combines a modified virus (CF33-CD19) and a cancer-fighting drug (blinatumomab, also known as Blincyto) to assess safety and tolerability. Participants will receive the treatment either directly into the tumor or through the bloodstream, with or without an additional drug called hydroxyurea. The trial seeks individuals with a confirmed diagnosis of advanced or metastatic solid tumors whose condition has progressed despite previous treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CF33-CD19, a virus targeting cancer cells, is being tested for safety and tolerability. This virus aims to attack cancer cells and boost the immune system's ability to fight tumors. So far, studies have tested CF33-CD19 alone and with blinatumomab.

Blinatumomab is already approved for some blood cancers, indicating its safety for those conditions. In this study, researchers are testing it with CF33-CD19 for solid tumors. As an early-stage trial focused on determining the right dose and assessing responses, safety information is still being collected.

Participants in earlier studies generally tolerated CF33-CD19 well, but specific side effects when combined with blinatumomab are still under investigation. This initial trial closely monitors for any side effects to ensure participant safety while testing this new treatment approach. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they uniquely combine CF33-CD19, an oncolytic virus, with Blinatumomab, a bispecific T-cell engager, to target solid tumors. Unlike standard options that often focus on chemotherapy or radiation, this approach uses a virus to selectively infect and kill cancer cells while simultaneously engaging the immune system to attack the tumor. Additionally, the treatments explore different methods of delivering CF33-CD19, either intravenously or intratumorally, which could optimize how effectively the cancer is targeted and eliminated. This dual-action strategy holds the potential for more precise and powerful cancer cell destruction compared to traditional treatments.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that CF33-CD19, a virus that attacks cancer, may help treat solid tumors. Early studies found that CF33-CD19 can specifically target and destroy cancer cells. In this trial, some participants will receive CF33-CD19 combined with blinatumomab, a drug that helps the immune system fight cancer. This combination has strengthened the body's defense against tumors. Although most evidence comes from early research, this approach could be promising for treating difficult cancers. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• CF33-CD19

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.

How Is the Trial Designed?

Group I: CF33-CD19 IV Administration in Combination with Blinatumomab and Hydroxyurea Experimental Treatment 3 Interventions

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

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

Group IV: CF33-CD19 IT Administration in Combination with Blinatumomab and Hydroxyurea Experimental Treatment 3 Interventions

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

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

Blinatumomab is already approved in European Union, United States for the following indications:

Approved in European Union as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• High-risk first relapse BCP-ALL

Approved in United States as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• First or second complete remission with minimal residual disease (MRD)

Who Is Running the Clinical Trial?

Imugene Limited

Lead Sponsor

Trials

7

Recruited

340+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2687

Combination therapy with the oncolytic virus CF33-CD19 ... Preclinical studies with CF33-CD19 have shown that combination therapy with CD19 targeting chimeric antigen receptor T cells is more effective ...

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/428416

A Study of onCARlytics (CF33-CD19) in Combination With ... This is an open-label, dose escalation and dose expansion, multi-center phase I study evaluating the safety and tolerability of CF33-CD19 administered ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-08528

A Study of onCARlytics (CF33-CD19) in Combination With ... This is an open-label, dose escalation and dose expansion, multi-center phase I study evaluating the safety and tolerability of CF33-CD19 administered ...

4. physicianresources.roswellpark.org physicianresources.roswellpark.org/news/investigators-hope-for-potential-breakthrough-in-dual-cellular-therapy-approach-for-advanced-and-metastatic-solid-tumors

Investigators Hope for Potential Breakthrough in Dual ... Preclinical studies have demonstrated that CF33-CD19 replicates selectively in tumor cells and marks them for destruction by causing them to ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT06063317

A Study of onCARlytics (CF33-CD19) in Combination With ... This development is part of the OASIS trial, which is designed to assess the safety and efficacy of Imugene's CD19 oncolytic virotherapy in patients with ...

6. imugene.com imugene.com/wp-content/uploads/2024/11/ASCOTIPOASIS.pdf

combination therapy with the oncolytic virus cf33-cd19 and ... CF33-CD19 DELIVERS TARGETS TO “TARGETLESS” SOLID TUMORS ... • To evaluate safety and tolerability of IV and IT CF33-CD19 in combination with blinatumomab.