Orca-T for Blood Cancers

(Orca-T Trial)

Not currently recruiting at 20 trial locations

Overseen By Anna Pavlova, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Orca Biosystems, Inc.

Must not be taking: Corticosteroids, Immunosuppressive therapy

Disqualifiers: Prior allogeneic HCT, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Orca-T for individuals with certain blood cancers. Orca-T, derived from special immune cells and stem cells from a healthy donor, aims to improve outcomes for patients undergoing a stem cell transplant. The trial compares Orca-T to the current standard treatment to determine which is safer and more effective. Individuals with specific blood cancers, such as acute leukemia or myelodysplastic syndromes, who plan to undergo a stem cell transplant, might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients the opportunity to access a potentially safer and more effective treatment.

Will I have to stop taking my current medications?

The trial requires that participants stop taking corticosteroids or other immunosuppressive therapy, except for topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day.

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

Research shows that Orca-T is generally manageable for patients. Studies have found this treatment to be less toxic than traditional stem cell transplants. Patients who received Orca-T experienced fewer serious side effects and had a lower risk of developing moderate-to-severe chronic graft-versus-host disease (cGvHD), where donor cells attack the patient's body.

Overall, previous studies have shown Orca-T to be safe, with better survival rates and fewer complications compared to standard treatments. This makes it a promising option for those considering clinical trials for blood cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for blood cancers, which typically involves an unmanipulated allograft from a donor combined with dual-agent prophylaxis, Orca-T offers a unique approach. This new treatment uses a refined cell therapy procedure with Orca-T, which is administered after a myeloablative conditioning regimen. What makes Orca-T stand out is its use of single-agent GVHD prophylaxis with tacrolimus following Tcon infusion, potentially reducing the risk of graft-versus-host disease while maintaining effectiveness. Researchers are excited because this could mean better outcomes and fewer side effects compared to existing treatments.

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

Research has shown that Orca-T, a treatment under study in this trial for blood cancers, is promising. In one study, patients treated with Orca-T had a one-year survival rate of 94%, surpassing the 83% for those receiving the standard-of-care treatment, another arm in this trial. Orca-T also correlates with better survival rates without chronic GVHD, a common transplant complication, compared to traditional methods. The treatment has demonstrated improved results in both younger and older patients. These findings suggest Orca-T might be a more effective option for patients undergoing stem cell transplants for blood cancers. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for people with certain blood cancers or pre-leukemia who are in remission, have a matched donor for stem cell transplant, and whose major organs function well. They must not be pregnant, breastfeeding, or unwilling to use birth control. People with recent other cancers, prior transplants, severe infections or certain viruses like HIV can't join.

Inclusion Criteria

Total bilirubin ≤ upper limit of normal (ULN)

Negative serum or urine beta-HCG test in females of childbearing potential

Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute

Exclusion Criteria

Psychosocial circumstances that preclude the patient from going through transplant or participating responsibly in follow-up care

Known allergy or hypersensitivity to, or intolerance of, tacrolimus

I am on low-dose corticosteroids or other immunosuppressive therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Participants undergo a myeloablative conditioning regimen followed by transplantation with either Orca-T or standard-of-care allograft

3-4 weeks

Initial Treatment and Prophylaxis

Participants receive GVHD prophylaxis with tacrolimus (and methotrexate for standard-of-care arm) starting around Day -3 to Day +3

4 weeks

Follow-up

Participants are monitored for safety and effectiveness, including survival and GVHD outcomes

730 days

What Are the Treatments Tested in This Trial?

Interventions

• Orca-T
• Standard-of-Care

Trial Overview The study compares Orca-T (an engineered graft of T cells) versus standard care in patients undergoing myeloablative allogeneic hematopoietic cell transplantation for blood cancers. It aims to assess the safety and effectiveness of this new treatment approach.

How Is the Trial Designed?

Group I: Orca-T Experimental Treatment 1 Intervention

For patients randomized to the Orca-T arm, Orca-T will be administered after myeloablative conditioning regimen. Single-agent GVHD prophylaxis with tacrolimus will be administered following Tcon infusion (generally Day +3).

Group II: Standard of Care alloHCT Control Active Control 1 Intervention

For patients randomized to the standard-of-care control arm, an unmanipulated allograft derived from the peripheral blood of a matched donor will be administered after a myeloablative conditioning regimen. Dual-agent prophylaxis consisting of tacrolimus plus methotrexate will be administered starting on Day -3.

Orca-T is already approved in United States for the following indications:

Approved in United States as Orca-T for:

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndrome (MDS)
• Myelofibrosis

Who Is Running the Clinical Trial?

Orca Biosystems, Inc.

Lead Sponsor

Trials

8

Recruited

750+

Citations

1. orcabio.com orcabio.com/orca-bio-announces-positive-results-from-the-pivotal-phase-3-study-of-investigational-orca-t-compared-to-allogeneic-stem-cell-transplant-for-the-treatment-of-hematologic-malignancies/

Press release Patients in the Orca-T group achieved an estimated overall survival (OS) of 94% compared to 83% in the alloHSCT arm at one year. "Today, ...

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/230/503053/Optimizing-Outcomes-with-Myeloablative

Efficacy and Safety of Precision Engineered Orca-T in Patients ... Overall survival was high at 100% and 96% at 12 months in the younger and older patients, respectively. There were two patients > 65 when they ...

3. onclive.com onclive.com/view/orca-t-delivers-major-gains-beyond-conventional-prophylaxis-in-hematologic-malignancies

Orca-T Delivers Major Gains Beyond Conventional ... Orca-T showed superior chronic GVHD-free survival and overall survival compared with conventional prophylaxis in the Precision-T trial. Long- ...

4. hematologyadvisor.com hematologyadvisor.com/news/fda-accepts-priority-review-la-orca-t-hematologic-malignancies-treatment-risk/

FDA Accepts Priority Review of BLA for Orca-T in ... Phase 3 trial data showed Orca-T led to a significant improvement in survival without moderate-to-severe chronic graft-versus-host disease ...

5. gvhdhub.com gvhdhub.com/medical-information/precision-t-a-phase-iii-trial-of-orca-t-vs-soc-for-cgvhd-prophylaxis-in-advanced-hematologic-malignancies

Precision-T: A phase III trial of Orca-T vs SoC for cGvHD ... Orca-T showed improved moderate-to-severe cGvHD-free survival and GRFS rates, and a lower incidence of SAEs, compared with Tac/MTX in patients with hematologic ...