ORCA-T for Blood Cancers

Overseen By Alyssa Kanegai

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Lori Muffly

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Prior allogeneic HCT, Uncontrolled infections, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 3-4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety of a new treatment called ORCA-T for individuals with certain blood cancers. ORCA-T is combined with two other medicines to prevent graft-versus-host disease (GVHD), where donor cells attack the patient's body post-transplant. The trial evaluates the effectiveness of this combination for patients in remission from acute leukemia or those with a specific type of myelodysplastic syndrome (MDS). It may suit those in remission from these diseases who have a donor match for a transplant. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking corticosteroids or other immunosuppressive therapy, except for topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day. If you have been exposed to a T cell-depleting agent, a washout period (time without taking certain medications) of 5 half-lives is required before the trial.

Is there any evidence suggesting that ORCA-T is likely to be safe for humans?

Research shows that people generally tolerate Orca-T well. Studies have found it causes fewer side effects than traditional transplants for blood cancers. One study discovered that Orca-T led to fewer serious side effects compared to standard treatments, meaning severe reactions were less common. The treatment also improved survival rates and reduced issues related to chronic graft-versus-host disease, a condition where donor cells attack the recipient's body.

Overall, Orca-T appears to be a safer and more manageable option compared to older treatments. However, since this trial is in its early stages, ensuring the safety of all participants remains a top priority. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for blood cancers, which often rely on chemotherapy or stem cell transplantation, ORCA-T is a novel approach that harnesses the power of T cells to target cancer cells more precisely. This treatment is unique because it combines T cell therapy with the immunosuppressive agents tacrolimus and ruxolitinib to potentially reduce the risk of graft-versus-host disease, a common complication in stem cell transplants. Researchers are excited about ORCA-T because it offers the possibility of a more targeted and potentially safer treatment option for blood cancer patients, aiming to improve outcomes and reduce side effects compared to conventional therapies.

What evidence suggests that ORCA-T might be an effective treatment for blood cancers?

Research has shown that ORCA-T, the investigational treatment in this trial, holds great promise for treating blood cancers. In one study, patients who received ORCA-T had a one-year survival rate of 94%, surpassing the 83% survival rate of those with traditional stem cell transplants. Another study found that ORCA-T patients had excellent survival rates at 12 months: 100% for younger patients and 96% for older ones. ORCA-T also enabled patients to survive without severe chronic graft-versus-host disease, a condition where transplanted cells attack the body. These results suggest that ORCA-T could be a highly effective treatment option for blood cancers. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with advanced blood cancers like various types of leukemia and myelodysplastic syndrome, who are planning to undergo allogeneic hematopoietic cell transplantation (HCT). Specific eligibility criteria details were not provided.

Inclusion Criteria

My kidney function is normal or only mildly reduced.

Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27%

Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 50%

Exclusion Criteria

Documented allergy or hypersensitivity to specific proteins

I do not have any ongoing serious infections.

I have had heart problems within a specific time frame.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Orca-T with dual agent GVHD prophylaxis, including tacrolimus and ruxolitinib

Approximately 3-4 weeks

Multiple visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on transplant-related adverse events

18 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• ORCA-T

Trial Overview The trial is testing the safety of a new treatment called ORCA-T when used alongside two other drugs meant to prevent graft-versus-host disease (GVHD) after an allogeneic HCT.

How Is the Trial Designed?

Group I: ORCA-T + (tacrolimus and ruxolitinib) Experimental Treatment 1 Intervention

Dual-agent tacrolimus starting on the day after Tcon infusion (Day +3 or Day +4) and ruxolitinib starting on the day after tacrolimus (Day +4 or Day +5).

Who Is Running the Clinical Trial?

Lori Muffly

Lead Sponsor

Trials

1

Recruited

20+

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Orca Biosystems, Inc.

Industry Sponsor

Trials

8

Recruited

750+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

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. orcabio.com orcabio.com/orca-bio-presents-three-year-survival-data-with-orca-t-in-patients-with-hematological-malignancies-at-the-66th-ash-annual-meeting/

Orca Bio Presents Three-Year Survival Data with Orca-T® ... Three-year overall survival with Orca-T allogeneic T-cell immunotherapy was 86% for patients with AML, ALL and MDS compared to 67% in a non-randomized ...

6. bloodcancerstoday.com bloodcancerstoday.com/post/fda-speedy-review-signals-confidence-in-orca-t-for-hematologic-malignancies

FDA Speedy Review Signals Confidence in Orca-T for ... Key results showed that at one year, the cGFS rate reached 78% (95% CI, 65.0%-86.6%) among patients in the Orca-T arm, compared with 38.4% (95% ...

7. 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 ...