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

Trial Summary

What is the purpose of this trial?

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 with CD33 and/or FLT3 expressing blood cancers, including AML and MDS.

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.

What safety data is available for SENTI-202 or similar treatments in humans?

Fedratinib, a treatment similar to SENTI-202, has been studied in patients with myelofibrosis and showed some common side effects like diarrhea, nausea, anemia (low red blood cell count), and vomiting. Serious side effects included one case of reversible liver failure and a rare brain condition called Wernicke's encephalopathy, but these were not common. Overall, fedratinib has shown an acceptable safety profile in clinical trials. ^{1 2 3 4 5}

Research Team

Rochelle Emery, MD

Principal Investigator

Senti Biosciences, Medical Director

Eligibility Criteria

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

I am fully active or can carry out light work.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase 2 randomized dose-ranging study of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of pacritinib and its potential in the treatment of hematologic disorders. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Association between acute myelogenous leukemia and thrombopoietin receptor agonists in patients with immune thrombocytopenia. [2021]

4. England 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. [2022]

5. United States 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. [2022]