SC291 for B-Cell Malignancies

Not currently recruiting at 9 trial locations

Overseen By Barbara Metallo

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sana Biotechnology

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS disorders, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SC291 for certain B-cell cancers, such as non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). The goal is to determine the safety and effectiveness of SC291 when combined with chemotherapy. The trial seeks participants who have had these cancers for some time and have not found success with other treatments. Those who have tried at least two different therapies and whose cancer has returned or not responded may be suitable for this study. As a Phase 1 trial, this research focuses on understanding how SC291 works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had systemic anticancer therapy or radiotherapy within 14 days of starting the trial (28 days for biologics).

Is there any evidence suggesting that SC291 is likely to be safe for humans?

A previous study administered SC291 to patients and showed early signs of safety and tolerability. Researchers found that SC291 targets cancer cells while reducing the risk of an immune reaction. Initial tests on patients indicated that SC291 could work without causing major side effects. Although promising, SC291 remains in an early testing phase, so researchers continue to closely monitor its safety. As this treatment is new and still under study, additional data will help confirm its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for B-cell malignancies, which usually involve chemotherapy or immunotherapy, SC291 represents a novel approach. Researchers are excited because SC291 is used after a conditioning regimen of fludarabine and cyclophosphamide, potentially enhancing its effectiveness. This investigational treatment might offer a new mechanism of action or improved targeting, aiming to make the therapy more effective or reduce side effects compared to existing options.

What evidence suggests that SC291 might be an effective treatment for B-Cell Malignancies?

Research shows that SC291, which participants in this trial will receive, is a promising treatment for certain blood cancers called B-cell malignancies. This treatment is a type of CAR T cell therapy, where immune cells are modified to attack cancer cells. SC291 specifically targets a protein called CD19 found on B cells, aiming to destroy these cancerous cells. Early studies have found that similar treatments focusing on CD19 can effectively treat B-cell cancers and may help shrink tumors. Although more research is needed, these early results suggest that SC291 could be a valuable option for patients with these types of cancers. ^{1 2 4 5 6}

Who Is on the Research Team?

John Gerecitano, MD, PhD

Principal Investigator

Sana Biotechnology, Inc.

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with certain B-cell malignancies, including various types of non-Hodgkin's lymphoma and chronic leukemias. Participants must have relapsed or refractory disease after at least two prior treatments or a stem cell transplant, be relatively fit (ECOG status 0 or 1), and have a life expectancy of at least 12 weeks.

Inclusion Criteria

I have a type of large B-cell lymphoma.

I have been diagnosed with marginal zone lymphoma.

I have been diagnosed with CLL or SLL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide

1 week

Treatment

Participants receive the investigational treatment SC291 following chemotherapy

24 months

Follow-up

Participants are monitored for safety, tolerability, and anti-tumor activity

24 months

What Are the Treatments Tested in This Trial?

Interventions

• SC291

Trial Overview The study is testing SC291, an investigational drug for B-cell malignancies. It's in Phase 1 to assess safety, how well it works against cancer, its effects on the body over time, potential immune reactions to it, and any biomarkers that might predict who benefits from it.

How Is the Trial Designed?

Group I: SC291 Plus Chemotherapy Regimen Experimental Treatment 1 Intervention

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment with SC291

Who Is Running the Clinical Trial?

Sana Biotechnology

Lead Sponsor

Trials

5

Recruited

12,100+

Published Research Related to This Trial

In a meta-analysis of 11,465 patients from 18 clinical trials, PD-1/PD-L1 inhibitors were found to significantly increase the risk of developing dermatologic adverse effects like rash and pruritus compared to chemotherapy, with relative risks of 1.84 and 3.74, respectively.

PD-1/PD-L1 inhibitors showed a lower risk of mucosal inflammation and alopecia compared to chemotherapy, indicating a distinct safety profile that differs from traditional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. Yang, W., Li, S., Yang, Q.[2021]

In a study of 103 patients with advanced cancer treated with combination anti-PD1/anti-CTLA4 therapies, 16.5% developed thyroid immune-related adverse events (irAEs), indicating that these side effects are relatively common and should be monitored regularly.

The occurrence of thyroid irAEs was associated with better overall survival rates, suggesting that these adverse events may have a positive prognostic significance in patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroid Immune-Related Adverse Events in Patients with Cancer Treated with anti-PD1/anti-CTLA4 Immune Checkpoint Inhibitor Combination: Clinical Course and Outcomes. Lui, DTW., Lee, CH., Tang, V., et al.[2022]

Adjuvant therapy with PD-1/PD-L1 inhibitors significantly improves overall survival (OS) and disease-free survival (DFS) in cancer patients, based on a meta-analysis of six randomized controlled trials involving 4,436 participants.

While these treatments offer substantial survival benefits, they are also associated with a higher risk of severe treatment-related adverse events (≥ grade 3), indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. Mo, DC., Liang, ZY., Chen, L., et al.[2022]

A meta-analysis of 21 studies involving 11,144 patients revealed that anti-CTLA4 therapy significantly increases the risk of various immune-related adverse events, such as diarrhea and colitis, with a relative risk of 2.43 to 11.39 for different conditions.

In contrast, while anti-PD1 therapy also raises the risk of pruritus (itching) with a relative risk of 4.01, it does not appear to increase the risk of other immune-related adverse events, highlighting the distinct safety profiles of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-Analysis of the Risk of Immune-Related Adverse Events With Anticytotoxic T-Lymphocyte-Associated Antigen 4 and Antiprogrammed Death 1 Therapies. Komaki, Y., Komaki, F., Yamada, A., et al.[2022]

In a study of 56 patients with advanced non-small-cell lung cancer (NSCLC) and concurrent autoimmune disease (AID) treated with PD-1 or PD-L1 inhibitors, 55% experienced an AID flare or immune-related adverse event (irAE), but most were manageable and did not lead to treatment discontinuation.

The overall response rate to PD-(L)1 therapy in this population was 22%, indicating that while there are risks, the treatment can still be effective for patients with NSCLC and AID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders. Leonardi, GC., Gainor, JF., Altan, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05878184

NCT05878184 | Study Evaluating SC291 in Subjects With r ... A Phase 1 Study Evaluating SC291, a Hypoimmune, Allogeneic CD19-directed CAR T Cell Therapy, in Relapsed and/or Refractory B-cell Malignancies (ARDENT).

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6852/500451/Phase-1-Study-of-SC291-a-Hypoimmune-Allogeneic

Phase 1 Study of SC291, a Hypoimmune, Allogeneic CD19 ... Phase 1 study of SC291, a hypoimmune, allogeneic CD19-directed CAR T cell therapy for relapsed/refractory B-cell malignancies (ARDENT) - initial clinical data.

3. cllsociety.org cllsociety.org/2024/09/early-study-of-experimental-car-t-therapy-for-b-cell-cancers/

Early Study of Experimental CAR-T Therapy for B Cell ... SC291 is an experimental CAR-T cell therapy made from healthy donor T cells, and it is being tested in an ongoing Phase I clinical trial. Who ...

4. withpower.com withpower.com/trial/phase-1-leukemia-lymphocytic-chronic-b-cell-4-2023-7ded4

SC291 for B-Cell Malignancies · Info for Participants What data supports the effectiveness of the treatment SC291 for B-Cell Malignancies? Research shows that targeting CD19, a marker found on B cells, is ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123134483

Phase 1 Study of SC291, a Hypoimmune, Allogeneic CD19 ... ARDENT is a phase 1 study evaluating safety and tolerability of SC291, a hypoimmune (HIP), allogeneic, CD19-directed CAR T cell therapy in subjects with Non- ...

6. ir.sana.com ir.sana.com/news-releases/news-release-details/sana-biotechnology-publishes-early-clinical-data-showing-sc291

Release Details - Investor Relations | Sana Biotechnology, Inc “These data suggest the potential of SC291 to persist and attack cancer cells ... SC291 as a therapeutic for patients with B-cell malignancies.