New cellular therapy for blood cancers in patients undergoing stem cell transplant

A Phase 1/2a Multicenter Ascending Dose Study to Evaluate the Safety of HA-1 Minor Histocompatibility Antigen-Reactive TCR-Modified T Cells (BSB-1001) in Patients Undergoing HLA-Matched Allogenic Hematopoietic Stem Cell Transplant for AML, ALL or MDS

This study is testing a new cell therapy called BSB-1001 to see if it can help prevent cancer from coming back in patients with high-risk blood cancers after they receive a stem cell transplant.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: BlueSphere Bio, Inc (industry)
• Drugs / interventions: CAR-T, chimeric antigen receptor, chemotherapy, radiation, fludarabine
• Locations: 6 sites (Duarte, California and 5 other locations)
• Trial ID: NCT06704152 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates BSB-1001, a TCR-modified T cell therapy derived from HLA-matched allogenic donors, for patients with high-risk blood cancers such as AML, ALL, and MDS undergoing hematopoietic stem cell transplant (HSCT). The study is designed as a first-in-human, multicenter, open-label, dose-finding trial to assess the safety and efficacy of BSB-1001 in preventing cancer relapse post-transplant. Patients will receive myeloablative conditioning followed by the infusion of BSB-1001 on day 0, with an adaptive dose escalation approach to determine the maximum tolerated dose. The trial aims to enroll patients who meet specific HLA and HA-1 criteria and will follow them until the study's completion.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with high-risk AML, ALL, or MDS who are undergoing HLA-matched allogenic HSCT.

Not a fit: Patients with low-risk hematologic malignancies or those not eligible for HSCT may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly reduce the risk of cancer relapse in patients undergoing stem cell transplants for blood cancers.

How similar studies have performed: Other studies using TCR-modified T cell therapies have shown promising results, indicating potential for success in this novel approach.

Eligibility criteria

Inclusion Criteria:

1. Male or female patients, ages 18 - 70 years inclusive, undergoing alloHCT.
2. Any of the following high-risk hematologic malignancies:

   1. AML diagnosed which has been treated with at least two lines of therapy\* Refractory or relapsed (CR, CRh or CRi,), including myeloblasts up to 25% OR MRD positive OR persistent disease-defining cytogenetic abnormality OR MRD-negative, but with high-risk disease For patients in remission meeting criteria a, consolidation regimens would be considered another line of therapy of eligibility purposes
   2. ALL which has been with abnormal lymphoblasts ≥5% and up to 25% in bone marrow OR persistent disease-defining cytogenetic abnormality or MRD positive
   3. MDS after at least one line of therapy, which includes hypomethylating agent(s) and must be high or very high risk by Revised International Prognostic Scoring System (IPSS-R), monosomy, or complex karyotype or TP53 mutation.
   4. In the expansion phase AML patients diagnosed which has been treated with at least two lines of therapy, and refractory or relapsed (CR, CRh or CRi,), including myeloblasts up to 25% OR MRD positive OR persistent disease-defining cytogenetic abnormality OR MRD-negative, but with high- risk disease
3. HLA-A\*02:01 AND HA-1 positive (either H/H or H/R).
4. Suitable for one of the approved conditioning regimens as defined in the protocol.
5. Patient must have an identified donor that is HA 1-negative with 10/10 matched related or unrelated donor

Exclusion Criteria:

1. Weight \> 100 kg.
2. Prior history of allogeneic stem cell transplantation
3. Prior history of autologous stem cell transplantation within 1 year prior to the planned dosing of BSB-1001 (day 0)
4. Previous genetically engineered chimeric antigen receptor T Cell therapy (CAR-T), approved or investigational, within 2 years of screening, with the exception of patients with ALL previously treated with an autologous CAR-T product.
5. Treatment with other investigational agents within 5 half-lives of the planned dosing of BSB-1001 (day 0).
6. History of treatment with checkpoint inhibitor therapy within 3 months of transplantation.
7. Other malignancy with life expectancy \< 1year.
8. Pregnant or lactating women.
9. Uncontrolled bacterial, viral, or fungal infections at time of enrollment.
10. Past or current viral infections as defined in the protocol.
11. CNS involvement refractory to intrathecal chemotherapy and/or standard cranial- spinal radiation. 12 Karnofsky Performance Score \< 60%.

13\. Inadequate organ function as defined in protocol.

Where this trial is running

Duarte, California and 5 other locations

• City of Hope National Medical Center — Duarte, California, United States (RECRUITING)
• Moffitt Cancer Center — Tampa, Florida, United States (RECRUITING)
• University of Michigan — Ann Arbor, Michigan, United States (RECRUITING)
• University of Minnesota — Minneapolis, Minnesota, United States (RECRUITING)
• Washington University at St Louis — St Louis, Missouri, United States (RECRUITING)
• The Ohio State University — Columbus, Ohio, United States (RECRUITING)

Study contacts

• Study coordinator: Medical Director: Nawazish Khan, MD, BlueSphere Bio

Conditions: AML, Adult Recurrent, ALL, Recurrent, Adult, MDS, TCR, T-cell therapy