A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies

• ClinicalTrials.gov Identifier: NCT05643742
• Recruitment Status: Recruiting
• First Posted: December 9, 2022
• Last Update Posted: August 15, 2023
• Sponsor: CRISPR Therapeutics AG
• Information provided by (Responsible Party): CRISPR Therapeutics ( CRISPR Therapeutics AG )

Tracking Information

• First Submitted Date: November 30, 2022
• First Posted Date: December 9, 2022
• Last Update Posted Date: August 15, 2023
• Actual Study Start Date: March 10, 2023
• Estimated Primary Completion Date: January 2030 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2022)

• Phase 1 (Dose Escalation): Incidence of adverse events, defined as dose-limiting toxicities [ Time Frame: From CTX112 infusion up to 28 days post-infusion ]
• Phase 2 (Cohort Expansion): Objective response rate [ Time Frame: From CTX112 infusion up to 60 months post-infusion ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 12, 2022)

• Duration of Response [ Time Frame: From date of first objective response of complete response (CR)/partial response (PR) until date of disease progression or death due to any cause, assessed up to 60 months ]
  Duration of Response (DOR) will only be reported for subjects who have had CR/PR events
• Duration of Clinical Benefit (DOCB) [ Time Frame: From date of first objective response of CR/PR until the relapse or death that followed the last response, assessed up to 60 months ]
• Progression Free Survival [ Time Frame: From date of CTX112 infusion until date of disease progression or death due to any cause, assessed up to 60 months ]
• Overall Survival [ Time Frame: From date of CTX112 infusion until date of death due to any cause, assessed up to 60 months ]

Original Secondary Outcome Measures (submitted: November 30, 2022)

• Duration of Response [ Time Frame: From date of first objective response of CR/PR until date of disease progression or death due to any cause, assessed up to 60 months ]
  Duration of Response (DOR) will only be reported for subjects who have had CR/PR events
• Duration of Clinical Benefit (DOCB) [ Time Frame: From date of first objective response of CR/PR until the relapse or death that followed the last response, assessed up to 60 months ]
• Progression Free Survival [ Time Frame: From date of CTX112 infusion until date of disease progression or death due to any cause, assessed up to 60 months ]
• Overall Survival [ Time Frame: From date of CTX112 infusion until date of death due to any cause, assessed up to 60 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies
• Official Title: A Phase 1/2, Open-Label, Multicenter, Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Anti-CD19 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX112) in Subjects With Relapsed or Refractory B Cell Malignancies
• Brief Summary: This is an open-label, multicenter, Phase 1/2 study evaluating the safety and efficacy of CTX112™ in subjects with relapsed or refractory B-cell malignancies.
• Detailed Description: This is an open-label, multi-center Phase 1/2 study of CTX112 in subjects with relapsed/refractory B cell malignancies. CTX112 is an is allogeneic CD19-directed chimeric antigen receptor (CAR) T cell immunotherapy comprised of allogeneic T cells that are genetically modified ex vivo using CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/ CRISPR associated protein 9) gene editing components (single guide RNA and Cas9 nuclease).
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• B-cell Lymphoma
• Non-Hodgkin Lymphoma
• B-cell Malignancy
• Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
• Follicular Lymphoma
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma
• Large B-cell Lymphoma

Intervention

Biological: CTX112

CTX112 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components)

Study Arms

Experimental: CTX112

Administered by IV infusion following lymphodepleting chemotherapy.

Intervention: Biological: CTX112

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 30, 2022): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2030
• Estimated Primary Completion Date: January 2030 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Age ≥18 years.
2. Refractory or relapsed B cell malignancy.
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 CTX112 infusion.

Key Exclusion Criteria:

1. Prior allogeneic hematopoietic stem cell transplant (HSCT).
2. Active or history of central nervous system (CNS) involvement by malignancy.
3. History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
4. Presence of bacterial, viral, or fungal infection that is uncontrolled or requires IV anti-infectives.
5. Active HIV, hepatitis B virus or hepatitis C virus infection.
6. 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.
7. Use of systemic anti-tumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of enrollment.
8. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
9. Women who are pregnant or breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials; +1 (877) 214-4634; MedicalAffairs@crisprtx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05643742
• Other Study ID Numbers: CRSP-ONC-006
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: CRISPR Therapeutics ( CRISPR Therapeutics AG )
• Original Responsible Party: Same as current
• Current Study Sponsor: CRISPR Therapeutics AG
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Annie Weaver, PhD; CRISPR Therapeutics

• PRS Account: CRISPR Therapeutics
• Verification Date: August 2023