Anitocabtagene Autoleucel for Multiple Myeloma

(iMMagine-3 Trial)

Recruiting at 36 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Kite, A Gilead Company

Must be taking: Immunomodulatory drugs, Anti-CD38 antibodies

Must not be taking: Systemic steroids, Immunosuppressive therapy

Disqualifiers: CNS involvement, Plasma cell leukemia, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The goal of this study (iMMagine-3) is to compare the study drug, anitocabtagene autoleucel to standard of care therapy (SOCT) in participants with relapsed/refractory multiple myeloma who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and an immunomodulatory drug. The primary objective of this study is to compare the efficacy of anitocabtagene autoleucel versus SOCT in participants with RRMM as measured by progression-free survival (PFS) per blinded independent review committee (IRC).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on high-dose steroids or other immunosuppressive therapy, you may need to stop them at least 14 days before joining the trial.

What data supports the effectiveness of the treatment Anitocabtagene Autoleucel for Multiple Myeloma?

Research on similar treatments, like ciltacabtagene autoleucel (cilta-cel), shows that BCMA-directed CAR T-cell therapies can be effective for patients with multiple myeloma who have tried many other treatments. These therapies have been approved for use and have shown positive results in clinical trials for similar conditions. ^{1 2 3 4 5}

Is Anitocabtagene Autoleucel safe for humans?

The research does not provide specific safety data for Anitocabtagene Autoleucel, but similar treatments like ciltacabtagene autoleucel have shown manageable safety profiles in patients with multiple myeloma, with potential side effects that are mostly manageable. ^{1 4 6 7 8}

What makes Anitocabtagene Autoleucel treatment unique for multiple myeloma?

Anitocabtagene Autoleucel is a novel CAR-T cell therapy that targets BCMA, a protein on the surface of multiple myeloma cells, and is designed to help the immune system attack these cancer cells. This treatment is unique because it uses a patient's own modified T-cells to specifically target and destroy cancer cells, offering a personalized approach compared to traditional therapies. ^{1 2 4 9 10}

Research Team

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Eligibility Criteria

This trial is for people with relapsed/refractory multiple myeloma who've had 1-3 prior treatments including an anti-CD38 antibody and an immunomodulatory drug. They should have measurable disease indicators, be able to receive one of the standard therapies, and have good physical function (ECOG status 0 or 1). Women must not be pregnant and if of childbearing potential, need a negative pregnancy test.

Inclusion Criteria

Key

I have been diagnosed with multiple myeloma.

I've had 1-3 prior treatments for myeloma, including specific types of therapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lymphodepletion chemotherapy followed by a single dose of anitocabtagene autoleucel or standard of care therapy

3-4 weeks

Post-treatment Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Long-term Follow-up

Participants transition to a separate long-term follow-up study to continue follow-up out to 15 years

Up to 15 years

Treatment Details

Interventions

• Anitocabtagene Autoleucel (CAR T-cell Therapy)

Trial Overview The study compares anitocabtagene autoleucel (a new therapy) against standard of care options like Bortezomib or Carfilzomib combinations in participants with multiple myeloma. It measures how long patients live without their disease getting worse by using independent reviews.

Participant Groups

Group I: Anitocabtagene Autoleucel Experimental Treatment 3 Interventions

Participants with RRMM will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days followed by single dose of anitocabtagene autoleucel chimeric antigen receptor positive (CAR+) on Day 1.

Group II: Standard of Care Therapy (SOCT) Active Control 5 Interventions

Participants will receive the investigator's choice of one of the following therapies: * pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles) * daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles) * carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles) * carfilzomib and dexamethasone (Kd) (28-day cycles)

Who Is Running the Clinical Trial?

Kite, A Gilead Company

Lead Sponsor

Trials

45

Recruited

4,300+

Arcellx, Inc.

Industry Sponsor

Trials

5

Recruited

650+

Findings from Research

Ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival in patients with lenalidomide-refractory multiple myeloma, with a median progression-free survival not reached in the cilta-cel group compared to 11.8 months in the standard-care group, based on a phase 3 trial with 419 participants.

The cilta-cel group also showed higher overall response rates (84.6% vs. 67.3%) and complete response rates (73.1% vs. 21.8%) compared to standard care, although most patients experienced grade 3 or 4 adverse events, including cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. San-Miguel, J., Dhakal, B., Yong, K., et al.[2023]

CAR-T therapies, specifically idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), show significant potential in treating heavily pretreated relapsed/refractory multiple myeloma (RRMM), with updated clinical trial data indicating they can elicit responses in these patients.

Indirect comparisons suggest that cilta-cel may provide deeper and more durable responses than ide-cel in patients with triple class-exposed RRMM, although direct head-to-head trials are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Use of Chimeric Antigen Receptor-Expressing T-Cell Therapies for Treatment of Multiple Myeloma. Martin, T., Jackson, CC., Pacaud, L., et al.[2023]

In a phase 3 trial with 386 patients suffering from relapsed and refractory multiple myeloma, idecabtagene vicleucel (ide-cel) significantly improved progression-free survival (13.3 months) compared to standard treatments (4.4 months), indicating its efficacy in this challenging patient population.

The treatment with ide-cel resulted in a 71% overall response rate, including a 39% complete response rate, although it was associated with high rates of adverse events (93% grade 3 or 4), including cytokine release syndrome in 88% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. Rodriguez-Otero, P., Ailawadhi, S., Arnulf, B., et al.[2023]

Ciltacabtagene autoleucel (cilta-cel) has been approved by the FDA as a fifth-line treatment option for patients with relapsed or refractory multiple myeloma, marking a significant advancement in therapy options for this challenging condition.

Cilta-cel is notable for being the second chimeric antigen receptor T-cell therapy targeting BCMA to receive regulatory approval within a year, highlighting the rapid development of innovative treatments in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilta-cel OK'd for Multiple Myeloma. [2022]

Ciltacabtagene autoleucel (cilta-cel) showed significantly improved progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) compared to physician's choice of treatment in patients with relapsed or refractory multiple myeloma, with hazard ratios indicating strong benefits (HR: 0.18 for PFS, HR: 0.15 for TTNT, HR: 0.25 for OS).

The study utilized real-world data from the Flatiron Health multiple myeloma cohort to compare cilta-cel's effectiveness, ensuring balanced baseline characteristics through inverse probability of treatment weighting, which supports the robustness of the findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of ciltacabtagene autoleucel in CARTITUDE-1 versus physician's choice of therapy in the Flatiron Health multiple myeloma cohort registry for the treatment of patients with relapsed or refractory multiple myeloma. Martin, T., Krishnan, A., Yong, K., et al.[2023]

In a retrospective analysis of 7 patients with prior allogeneic stem cell transplants (alloSCT) who received cilta-cel, an overall response rate of 85.7% was observed, indicating that cilta-cel is effective even in this heavily pretreated group.

The safety profile of cilta-cel in patients with prior alloSCT was similar to that of patients without alloSCT, with manageable side effects like cytokine release syndrome and no reported cases of graft-versus-host disease, suggesting that cilta-cel may be a viable treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene Autoleucel in Patients With Prior Allogeneic Stem Cell Transplant in the CARTITUDE-1 Study. Htut, M., Dhakal, B., Cohen, AD., et al.[2023]

Ciltacabtagene autoleucel (cilta-cel) is a CAR T-cell therapy that effectively targets B-cell maturation antigen (BCMA) in patients with relapsed or refractory multiple myeloma, showing early and long-lasting responses based on the Phase 1b/2 CARTITUDE-1 study.

While cilta-cel has a tolerable safety profile with manageable adverse effects, it generally demonstrates better efficacy compared to another CAR T-cell therapy, idecabtagene vicleucel (ide-cel), although both therapies have comparable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. Chekol Abebe, E., Yibeltal Shiferaw, M., Tadele Admasu, F., et al.[2022]

Ciltacabtagene autoleucel (cilta-cel) demonstrated a significantly higher overall response rate (84% vs. 28%) and longer progression-free survival in patients with relapsed/refractory multiple myeloma compared to standard non-CAR-T therapies, based on a comparison of 113 patients in the CARTITUDE-1 study and 190 patients from the MAMMOTH dataset.

In the modified intent-to-treat population, cilta-cel showed an even more impressive overall response rate of 96% compared to 30% in the MAMMOTH cohort, indicating its potential as a highly effective treatment option for patients who have exhausted other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma. Costa, LJ., Lin, Y., Cornell, RF., et al.[2022]

Ciltacabtagene autoleucel (cilta-cel) demonstrated significantly better efficacy compared to physician's choice of treatment in patients with relapsed or refractory multiple myeloma, with a relative risk of 2.95 for overall response rate and 111.70 for complete response or better.

The study showed that cilta-cel also improved progression-free survival and overall survival, with hazard ratios of 0.24 and 0.21 respectively, indicating it could be a promising new treatment option for patients who have already been exposed to multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Ciltacabtagene Autoleucel in CARTITUDE-1 vs Physician's Choice of Therapy in the Long-Term Follow-Up of POLLUX, CASTOR, and EQUULEUS Clinical Trials for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. Weisel, K., Martin, T., Krishnan, A., et al.[2022]

References

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

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. [2023]

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

Recent Advances in the Use of Chimeric Antigen Receptor-Expressing T-Cell Therapies for Treatment of Multiple Myeloma. [2023]

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

Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. [2023]

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

Cilta-cel OK'd for Multiple Myeloma. [2022]

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

Comparative effectiveness of ciltacabtagene autoleucel in CARTITUDE-1 versus physician's choice of therapy in the Flatiron Health multiple myeloma cohort registry for the treatment of patients with relapsed or refractory multiple myeloma. [2023]

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

Ciltacabtagene Autoleucel in Patients With Prior Allogeneic Stem Cell Transplant in the CARTITUDE-1 Study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. [2021]

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

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. [2022]

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

Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Ciltacabtagene Autoleucel in CARTITUDE-1 vs Physician's Choice of Therapy in the Long-Term Follow-Up of POLLUX, CASTOR, and EQUULEUS Clinical Trials for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. [2022]