A Phase 1 Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Anti-BCMA Allogeneic CRISPR-Cas9-Engineered T Cells (CTX120) in Subjects With Relapsed or Refractory Multiple Myeloma

Plain English Summary

A Safety and Efficacy Study Evaluating CTX120 in Subjects With Relapsed or Refractory Multiple Myeloma is a Phase 1 clinical trial sponsored by CRISPR Therapeutics AG studying Multiple Myeloma. This trial tested a new gene-edited cell therapy called CTX120 for patients with multiple myeloma that has returned or stopped responding to treatment. It was designed for adults with relapsed or refractory multiple myeloma who had already tried at least two other treatments. Participation involved receiving CTX120, with close monitoring for side effects and treatment effectiveness. Alternative treatments for this condition include other types of chemotherapy, targeted therapies, and stem cell transplants. The trial aims to enroll 26 participants.

Official Summary

This is a single-arm, open-label, multicenter, Phase 1 study evaluating the safety and efficacy of CTX120 in subjects with relapsed or refractory multiple myeloma.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with multiple myeloma that has returned or is no longer responding to treatment, and who have had at least two prior therapies. Patients must have good general health, with adequate kidney, liver, heart, and lung function. Individuals who have had a stem cell transplant before, or have received prior gene therapy or BCMA-directed therapy, cannot participate. Those with active infections or certain other medical conditions, like recent heart problems or brain involvement from myeloma, are also excluded. This trial is studying Multiple Myeloma, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcomes measured how often serious side effects occurred and how well the treatment worked in shrinking tumors, which helps understand the therapy's safety and potential benefit. The specific primary outcome measures are: Part A (dose escalation): Incidence of adverse events (From CTX120 infusion up to 28 days post-infusion); Part B (cohort expansion): Objective response rate (From CTX120 infusion up to 60 months post-infusion). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial aimed to explore a novel gene-editing approach for a difficult-to-treat blood cancer, addressing a significant unmet need in multiple myeloma therapy. This research targets Multiple Myeloma, where improved treatment options are needed.

Investor Insight

The termination of this Phase 1 trial suggests potential safety or efficacy concerns, impacting CRISPR Therapeutics' pipeline for BCMA-targeted therapies in a competitive oncology market. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of CTX120, and what to expect during and after treatment. Be prepared for regular clinic visits for monitoring, blood tests, and potential side effect management. Understand that this is an experimental treatment, and its effectiveness and long-term effects are still being studied. The trial is being conducted at 10 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 26 participants

Interventions

• BIOLOGICAL: CTX120 — CTX120 B-cell maturation antigen (BCMA)-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components.

Primary Outcomes

• Part A (dose escalation): Incidence of adverse events (From CTX120 infusion up to 28 days post-infusion)
• Part B (cohort expansion): Objective response rate (From CTX120 infusion up to 60 months post-infusion)

Secondary Outcomes

• Progression Free Survival (From date of CTX120 infusion and date of disease progression or death due to any cause, assessed up to 60 months)
• Overall Survival (From date of CTX120 infusion until date of death due to any cause, assessed up to 60 months)

Full Eligibility Criteria

Key Inclusion Criteria:

1. Age ≥18 years.
2. Relapsed or refractory multiple myeloma, as defined by IMWG response criteria and treatment with at least 2 prior lines of therapy.
3. Eastern Cooperative Oncology Group performance status 0 or 1.
4. Adequate renal, liver, cardiac and pulmonary organ function
5. Female subjects of childbearing potential and male subjects must agree to use acceptable method(s) of contraception from enrollment through at least 12 months after CTX120 infusion.

Key Exclusion Criteria:

1. Prior allogeneic stem cell transplant (SCT).
2. Less than 60 days from autologous SCT at time of screening and with unresolved serious complications.
3. Prior treatment with any gene therapy or genetically modified cell therapy, including CAR T cells or natural killer cells, or BCMA-directed therapy.
4. Evidence of direct central nervous system (CNS) involvement by multiple myeloma.
5. History or presence of clinically relevant CNS pathology such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement.
6. Unstable angina, clinically significant arrhythmia, or myocardial infarction within 6 months of enrollment.
7. Active HIV, hepatitis B virus or hepatitis C virus infection.
8. Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥5 years.
9. Use of systemic anti-tumor therapy or investigational agent within 14 days prior to enrollment.
10. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
11. Women who are pregnant or breastfeeding.

Trial Locations

• University of Chicago, Chicago, Illinois, United States
• Oregon Health and Science University, Portland, Oregon, United States
• University of Pennsylvania, Philadelphia, Pennsylvania, United States
• Sarah Cannon Research Institute, Nashville, Tennessee, United States
• Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
• Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
• University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
• Institut Catala d'Oncologia Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
• Universidad de Navarra, Pamplona, Navarre, Spain
• Hospital Universitario de Salamanca, Salamanca, Spain

Frequently Asked Questions

Related Conditions

• Multiple Myeloma
• Relapsed Multiple Myeloma
• Refractory Multiple Myeloma
• Plasma Cell Neoplasms
• Hematologic Malignancies
• Bone Marrow Diseases
• Cancer
• Blood Cancers
• Immunotherapy
• Gene Therapy

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