SENTI-202 for Blood Cancers

Recruiting at 7 trial locations

Overseen By Rochelle Emery, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Senti Biosciences

Disqualifiers: Leukemia, MDS-f, CNS disease, others

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

Compensation: Varies

Number of Visits: 28

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called SENTI-202 for certain blood cancers. SENTI-202 is a specialized cell therapy designed to target and fight cancer cells. The trial includes individuals with specific blood cancers, such as relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), who have not succeeded with other treatments. Ideal participants have cancer with specific markers (CD33 or FLT3) and have experienced a relapse after previous therapies. Participants must have stable organ function and be able to recover well from past treatments. As a Phase 1 trial, this research aims to understand how SENTI-202 works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Do I need to stop my current medications for the SENTI-202 trial?

The trial protocol does not specify if you need to stop your current medications, but it mentions that certain anti-cancer therapies used within a specific time before the study are not allowed. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that SENTI-202 is likely to be safe for humans?

Research has shown that SENTI-202 has promising safety results from early studies. All three patients who received SENTI-202 tolerated it well. The side effects resembled those typically seen with lymphodepleting chemotherapy, which prepares the body to receive new cells. This indicates no unexpected or severe reactions specifically linked to SENTI-202.

Additionally, researchers found SENTI-202 in all treated patients, indicating it functions like other similar treatments. This is a positive sign, as it shows the treatment is working as expected without causing major problems. Since this is an early trial, the main goal is to ensure the treatment's safety for people. So far, the results are encouraging, suggesting SENTI-202 could be a safe option for treating certain blood cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for blood cancers, which often include chemotherapy and stem cell transplants, SENTI-202 is a novel CAR NK cell therapy. This treatment is particularly exciting because it uses engineered natural killer (NK) cells to specifically target and eliminate cancer cells, potentially offering a more precise approach. Researchers are also interested in its potential for fewer side effects compared to traditional therapies, as CAR NK cells may spare healthy cells more effectively. This innovative approach could lead to more effective and better-tolerated treatments for patients with blood cancers.

What evidence suggests that SENTI-202 might be an effective treatment for blood cancers?

Research has shown that SENTI-202, a new type of cell therapy, may help treat certain blood cancers like AML (acute myeloid leukemia). Early studies found that SENTI-202 can specifically target and destroy both regular leukemia cells and the more difficult-to-treat leukemia stem cells. Some AML patients who did not respond to other treatments went into complete remission after receiving SENTI-202. This trial will explore SENTI-202 CAR NK cell therapy, which uses a special technology to more accurately target cancer cells. These findings suggest that SENTI-202 could be a promising option for patients with challenging blood cancers. ^{2 3 6 7 8}

Who Is on the Research Team?

Rochelle Emery, MD

Principal Investigator

Senti Biosciences, Medical Director

Are You a Good Fit for This Trial?

This trial is for adults with blood cancers like AML or MDS that have come back after treatment. They must have tried at least one, but no more than two or three treatments (depending on the condition), and their cancer cells need to show CD33 or FLT3 markers. Participants should be fairly active (ECOG score 0-1) and have decent organ function.

Inclusion Criteria

I have recovered from side effects of my previous cancer treatments.

Documentation of CD33 expression (or FLT3 expression if available) by individual institutional standard of care

Willing and able to provide written informed consent

Exclusion Criteria

I have leukemia in my brain or active brain disease.

White blood cell (WBC) count of ≥20×109/L or circulating blasts ≥10×109/L or rapidly progressive/hyperproliferative disease

My cancer involves organs outside the bone marrow without signs of returning in the blood.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to SENTI-202 administration

1-2 weeks

Dose Finding

Sequential cohorts receive doses of SENTI-202 using a modified 3+3 study design to determine the recommended phase 2 dose

28 days per cycle

Visits at the end of each 28-day cycle

Cohort Expansion

Additional subjects are enrolled in disease-specific expansion cohorts at the recommended phase 2 dose to further explore safety, biodynamics, and anti-cancer activity

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• SENTI-202

Trial Overview SENTRI-202, a new type of cell therapy using modified natural killer (NK) cells designed to target cancer cells in patients with specific proteins on their leukemia or tumor cells, is being tested for safety and effectiveness.

How Is the Trial Designed?

Group I: SENTI-202 CAR NK cell therapy Experimental Treatment 1 Intervention

Part 1 Dose Finding: Sequential cohorts will receive doses of SENTI-202 using a modified 3+3 study design to determine the recommended phase 2 dose (RP2D). The starting dose will be 1 billion cells. Other doses may be explored depending on study data. Part 2 Cohort Expansion: After determination of the RP2D, additional subjects will be enrolled in disease-specific expansion cohorts at that dose to further explore safety, biodynamics, and anti-cancer activity of SENTI-202

Who Is Running the Clinical Trial?

Senti Biosciences

Lead Sponsor

Trials

2

Recruited

30+

Published Research Related to This Trial

A study of 4,821 immune thrombocytopenic purpura (ITP) patients found an association between the use of thrombopoietin receptor (MPL) agonists and the development of acute myelogenous leukemia (AML), with 1.74% of patients treated with romiplostim and 1.52% with eltrombopag developing AML.

Despite this association, the authors caution that due to potential biases and incomplete data in the FDA Adverse Event Reporting System, further research is needed before making any changes to prescribing practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between acute myelogenous leukemia and thrombopoietin receptor agonists in patients with immune thrombocytopenia. Oshima, Y., Yuji, K., Tanimoto, T., et al.[2021]

In a phase 2 study involving 31 patients with high-risk myelofibrosis, fedratinib showed significant efficacy in reducing spleen size, with a maximum reduction of 43.3% at the highest dose (500 mg) after 12 weeks.

While fedratinib demonstrated clinical activity, it was associated with serious adverse events, including cases of Wernicke's encephalopathy, leading to the discontinuation of its clinical development program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 randomized dose-ranging study of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis. Pardanani, A., Tefferi, A., Jamieson, C., et al.[2022]

In a pivotal phase III trial, fedratinib, an oral JAK2 inhibitor, demonstrated significant efficacy in treating myelofibrosis, with a 47% spleen volume response rate and a 40% symptom response rate at 24 weeks, compared to only 1% and 9% for placebo.

Fedratinib was generally well-tolerated, with common side effects including diarrhea, nausea, anemia, and vomiting, but notably, there were no cases of Wernicke encephalopathy reported in patients taking the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated results of the placebo-controlled, phase III JAKARTA trial of fedratinib in patients with intermediate-2 or high-risk myelofibrosis. Pardanani, A., Tefferi, A., Masszi, T., et al.[2022]

In the phase II JAKARTA2 study involving 97 patients with intermediate- or high-risk myelofibrosis who were resistant or intolerant to ruxolitinib, fedratinib demonstrated a spleen volume response rate of 31%, indicating its efficacy in reducing spleen size.

Despite the positive outcomes, the treatment was associated with significant side effects, including grade 3-4 anemia in 38% of patients and thrombocytopenia in 22%, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fedratinib in patients with myelofibrosis previously treated with ruxolitinib: An updated analysis of the JAKARTA2 study using stringent criteria for ruxolitinib failure. Harrison, CN., Schaap, N., Vannucchi, AM., et al.[2022]

Pacritinib is a selective inhibitor of Janus kinase 2 and FMS-related tyrosine kinase 3, showing potential for treating blood cancers like myeloproliferative neoplasias and acute myeloid leukemia, with strong antiproliferative effects and the ability to induce cell death.

In early-phase clinical trials, pacritinib demonstrated promising efficacy and an acceptable safety profile, with mild to moderate gastrointestinal issues being the most common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of pacritinib and its potential in the treatment of hematologic disorders. Hatzimichael, E., Tsolas, E., Briasoulis, E.[2022]

Citations

1. investors.sentibio.com investors.sentibio.com/news-releases/news-release-details/senti-bio-present-updated-clinical-results-first-class-logic

Senti Bio to Present Updated Clinical Results of First-in- ... Two presentations, including one oral session, build on existing data and show deep and durable clinical remission rates, combined with a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06325748

SENTI-202: Off-the-shelf Logic Gated CAR NK Cell ... This is an open-label study of the safety, biodynamics, and anti-cancer activity of SENTI-202 (an off-the-shelf logic gated CAR NK cell therapy) in patients ...

3. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT014/762477/Abstract-CT014-First-in-human-multicenter-study-of

First-in-human, multicenter study of SENTI-202, a CD33/FLT3 ... Preclinical studies have shown that SENTI-202, a first-in-class CAR NK cell therapy, selectively kills AML blasts and leukemia stem cells (LSCs) ...

4. aacr.org aacr.org/about-the-aacr/newsroom/news-releases/off-the-shelf-car-natural-killer-cell-therapy-with-logic-gates-elicits-complete-remissions-in-relapsed-or-refractory-blood-cancers/

Off-the-shelf CAR Natural Killer Cell Therapy with Logic ... Several patients with AML, who were treated with SENTI-202 experienced a complete remission after not responding to or having relapsed ...

5. onclive.com onclive.com/view/investigation-of-senti-202-in-r-r-aml-continues-after-confirming-rp2d

Investigation of SENTI-202 in R/R AML Continues After ... In the dose-finding portion of the trial, patients received SENTI-202 following a lymphodepletion regimen featuring fludarabine and cytarabine.

6. investors.sentibio.com investors.sentibio.com/news-releases/news-release-details/senti-bios-senti-202-first-class-shelf-logic-gated-selective

Senti Bio's SENTI-202, a First-in-Class Off-the-Shelf Logic ... SENTI-202 was detected in all treated patients, consistent with other allogeneic CAR NK cell therapy PK profiles, namely with modest expansion ...

7. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/4531/492516/Senti-202-a-Selective-Off-the-Shelf-Preclinical

Senti-202, a Selective, Off-the-Shelf, Preclinical CAR-NK Cell ... A selective, off-the-shelf, preclinical CAR-NK cell therapy with CD33 and/or FLT3 activating CAR, healthy cell protection from endomucin (EMCN) inhibitory CAR.

8. sentibio.com sentibio.com/research-pipeline/products/

Products - Senti Bio In all three patients, SENTI-202 was well-tolerated with an adverse event profile consistent with the use of lymphodepleting chemotherapy in patients with AML.