CLN-049 for Leukemia and Myelodysplastic Syndrome

Recruiting at 8 trial locations

Overseen By Timna Serino

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cullinan Therapeutics Inc.

Must not be taking: Immunotherapy, CAR-T, Glucocorticoids, others

Disqualifiers: APL, CNS leukemia, Organ allograft, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CLN-049 (a FLT3 x CD3 bispecific antibody) for individuals with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who have not responded to other treatments. The study aims to determine the treatment's safety and effective administration. Participants will receive CLN-049 in varying doses, either through an IV or injection. This trial may suit those with recurrent or resistant AML or MDS who have exhausted other treatment options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like radiation therapy, immunotherapy, and some growth factors must be stopped before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that CLN-049 is likely to be safe for humans?

Research has shown that CLN-049 has promising safety results in early animal tests. These studies found that CLN-049 was generally well-tolerated, meaning most subjects did not experience severe side effects.

Since this is the first time CLN-049 is being tested in humans, it's important to note that researchers are still assessing its safety for people. The trial aims to find the safest dose for individuals with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

The trial administers the treatment using two main methods: through an IV (a tube into a vein) and as an injection under the skin. Researchers are carefully monitoring both methods to observe patient responses. While the study remains in an early stage, results from animal testing provide hope that CLN-049 could also be safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CLN-049 for leukemia and myelodysplastic syndrome because it offers a potentially new approach to treatment. Unlike standard chemotherapy treatments, which broadly attack rapidly dividing cells, CLN-049 is designed to target specific proteins found on cancer cells, potentially reducing damage to healthy cells. The treatment is being explored in two different delivery methods: intravenous (IV) and subcutaneous (SC) administration, which could offer more flexibility and convenience for patients. This targeted approach and versatile administration could lead to more effective and less toxic treatments, making it a promising option for patients with relapsed or refractory conditions.

What evidence suggests that CLN-049 could be an effective treatment for AML or MDS?

Research has shown that CLN-049 holds potential for treating relapsed or hard-to-treat acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This treatment uses a special type of antibody to help the immune system locate and attack cancer cells by targeting specific proteins. In this trial, participants will receive CLN-049 in different dosing regimens: Part A uses a single ascending dose (SAD) design administered intravenously, Part B uses a multiple ascending dose (MAD) design administered intravenously, and Part C uses a multiple ascending dose (MAD) design administered subcutaneously. Early human studies focus primarily on determining the right dosage and ensuring safety. Although human trial data is limited, initial lab results suggest that CLN-049 could be a promising treatment option for AML and MDS. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults diagnosed with recurrent or resistant AML or MDS, who have an ECOG performance status of 0-2 and adequate organ function. They must not have had certain treatments recently, like CAR-T therapy or allogeneic hematopoietic transplantation within six months. Participants need to be able to consent and follow the trial procedures.

Inclusion Criteria

Willing and able to give written informed consent and adhere to protocol requirements

The patient's laboratory values meet specific criteria for Creatinine clearance, Total bilirubin, AST, and ALT

Side effects from my previous cancer treatment have mostly gone away.

Exclusion Criteria

QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≥ 480 milliseconds

I don't have any health issues that could make the treatment unsafe for me.

Specific restrictions related to pregnancy and contraception

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Patients receive a single dose of CLN-049 via IV administration and are followed for safety

4 weeks

1 visit (in-person)

Multiple Ascending Dose (MAD) - IV

Patients receive CLN-049 every 7 days via IV administration after an initial Lead-In Dose and are followed for safety

4 weeks

4 visits (in-person)

Multiple Ascending Dose (MAD) - SC

Patients receive CLN-049 every 7 days via SC injection and are followed for safety

4 weeks

4 visits (in-person)

Long-term Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• CLN-049

Trial Overview The study is testing CLN-049 in a Phase 1 trial for patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) that has come back or hasn't responded to treatment. It's an open-label, multicenter trial where everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: Part C - Multiple ascending dose (MAD) design of SC administered CLN-049 Experimental Treatment 1 Intervention

Patients with relapsed/refractory AML or MDS will receive CLN-049 via SC injection

Group II: Part B - Multiple ascending dose (MAD) design of IV administered CLN-049 Experimental Treatment 1 Intervention

Patients with relapsed/refractory AML or MDS will receive CLN-049 via IV administration

Group III: Part A - Single ascending dose (SAD) design of IV administered CLN-049 Experimental Treatment 1 Intervention

Patients with relapsed/refractory AML or MDS will receive CLN-049 via IV administration

CLN-049 is already approved in United States for the following indications:

Approved in United States as CLN-049 for:

• Relapsed/Refractory Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndrome (MDS)

Who Is Running the Clinical Trial?

Cullinan Therapeutics Inc.

Lead Sponsor

Trials

9

Recruited

1,000+

Cullinan Oncology Inc.

Lead Sponsor

Trials

6

Recruited

710+

Cullinan Oncology, LLC

Lead Sponsor

Trials

7

Recruited

990+

Published Research Related to This Trial

The study identified three fully human antibodies (EB10, A2IN, and D4-3) that specifically target the FLT3 receptor, which is crucial for the survival of leukemia cells, indicating their potential as effective therapies for FLT3-expressing leukemia.

EB10 and D4-3 were particularly effective, blocking ligand binding and inhibiting cell proliferation in leukemia cells, suggesting they could be developed into treatments either alone or combined with cytotoxic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-based selection of internalizing fully human antagonistic antibodies directed against FLT3 for suppression of leukemia cell growth. Williams, B., Atkins, A., Zhang, H., et al.[2013]

Bispecific antibodies, like blinatumomab, are innovative immunotherapy treatments that engage immune cells to target and destroy tumor cells, specifically approved for Ph-negative B-cell acute lymphoblastic leukemia.

While bispecific antibodies have an acceptable safety profile, they can cause side effects such as neurotoxicity and cytokine-release syndrome, which are important considerations in their use for treating hematological malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bispecific antibodies in onco-hematology: Applications and perspectives]. Barrière, S., El-Ghazzi, N., Garcia, M., et al.[2021]

The newly developed bispecific FLT3 X CD3 antibody, 4G8 X UCHT1 Fabsc, shows superior affinity and production yield compared to traditional bispecific formats, making it a promising candidate for targeting leukemic cells.

In patient-derived primary blood samples, the 4G8 X UCHT1 Fabsc antibody effectively activated T cells and killed acute myeloid leukemia (AML) cells, outperforming a previously optimized monospecific FLT3 antibody, highlighting its potential for enhanced therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of a bispecific FLT3 X CD3 antibody in an improved, recombinant format for the treatment of leukemia. Durben, M., Schmiedel, D., Hofmann, M., et al.[2018]

Mesothelin (MSLN) is highly expressed on leukemic cells in a subset of pediatric AML patients, making it a promising target for immunotherapy, particularly with bispecific antibodies (BsAbs) that engage T-cells.

Two engineered MSLN/CD3-targeting BsAbs demonstrated significant efficacy in reducing leukemic burden and inducing complete remission in patient-derived xenograft models, suggesting they could be safe and effective treatment options for MSLN-positive pediatric AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapeutic Targeting of Mesothelin Positive Pediatric AML Using Bispecific T Cell Engaging Antibodies. Gopalakrishnapillai, A., Correnti, CE., Pilat, K., et al.[2022]

Bispecific antibodies (BiAB) that target the CD123 antigen can redirect T-cell activity against malignant cells in high-risk myelodysplastic syndrome (MDS) patients, potentially delaying disease progression.

These BiABs may also reduce the risk of leukemic transformation to secondary acute myeloid leukemia (AML), highlighting their promise as a new treatment strategy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD123-Directed Bispecific Antibodies for Targeting MDS Clones and Immunosuppressive Myeloid-Derived Suppressor Cells (MDSC) in High-Risk Adult MDS Patients. Uckun, FM., Watts, J.[2022]

The bispecific antibody 7370 targets FLT3 on acute myeloid leukemia (AML) cells and shows high potency in killing these cells in both laboratory and animal models, making it a promising treatment option for a broader range of AML patients.

7370 effectively activates T cells from AML patients, enhancing their ability to attack leukemia cells, and has been well tolerated in animal studies, indicating potential for safe use in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Optimized Full-Length FLT3/CD3 Bispecific Antibody Demonstrates Potent Anti-leukemia Activity and Reversible Hematological Toxicity. Yeung, YA., Krishnamoorthy, V., Dettling, D., et al.[2021]

Bispecific antibodies, like blinatumomab, are showing promise in treating relapsed and refractory hematological malignancies by creating artificial connections between tumor cells and T cells, enhancing the immune response against cancer.

Future treatments may involve combining bispecific antibodies with traditional chemotherapy or stem-cell transplants, aiming to improve efficacy while managing potential side effects like cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recent progress of bispecific antibody-based therapy for hematological malignancies]. Ochi, T.[2022]

A new bispecific antibody targeting CLL-1 has been developed for treating acute myeloid leukemia (AML), showing potential for effective treatment while sparing hematopoietic stem cells, which is crucial for patient recovery.

In preclinical studies, a low-affinity CD3/CLL-1 TDB was well tolerated in monkeys and effectively depleted target cells, suggesting that careful engineering of the antibody can enhance safety and efficacy in AML treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-CD3/anti-CLL-1 bispecific antibody for the treatment of acute myeloid leukemia. Leong, SR., Sukumaran, S., Hristopoulos, M., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05143996

Study Details | NCT05143996 | CLN-049 in Patients With ... This trial is divided into 3 parts: Part A - Single Ascending Dose (SAD) - Patients will receive a single dose of CLN-049 via IV administration and be ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10430354/

PB1847: A PHASE 1 STUDY TO INVESTIGATE CLN-049, ... This phase 1, first-in-human study is designed to define the dosing regimen and assess the safety of CLN-049 in pts with R/R AML or MDS.

3. cullinantherapeutics.com cullinantherapeutics.com/wp-content/uploads/2023/01/e003882.full_.pdf

A novel IgG-based FLT3xCD3 bispecific antibody for the ... Conclusions CLN- 049 has a favorable efficacy and safety profile in preclinical models, warranting evaluation of its antileukemic activity in ...

4. researchgate.net researchgate.net/publication/373356136_PB1847_A_PHASE_1_STUDY_TO_INVESTIGATE_CLN-049_A_FLT3CD3_BISPECIFIC_T_CELL_ENGAGER_IN_PATIENTS_WITH_RELAPSEDREFRACTORY_RR_ACUTE_MYELOID_LEUKEMIA_AML_OR_MYELODYSPLASTIC_SYNDROME_MDS

pb1847: a phase 1 study to investigate cln-049, a flt3/cd3 ... A phase 1 study of the FLT3/CD3 bispecific engager CLN-049 was recently reported [54] . This first-in-human study in patients with relapsed/refractory AML and ...

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-flt3-cd3-bispecific-antibody-cln-049?pn=1

Clinical Trials Using Anti-FLT3/CD3 Bispecific Antibody ... Review the clinical trials studying anti-flt3/cd3 bispecific antibody cln-049 on this list and use the filters to refine the results by age and location.

6. dukecancerinstitute.org dukecancerinstitute.org/clinical-trials/phase-1-open-label-pk-safety-study-cln-049-acute-myeloid-leukemiamyelodysplastic

Phase 1 Open Label, PK, Safety study of CLN-049 (Acute ... We are doing this study to find the most effective, safe dose of an experimental drug called CLN-049 (the study drug) for people with acute myeloid leukemia ( ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7054815/

An Optimized Full-Length FLT3/CD3 Bispecific Antibody ... We developed an anti-FLT3-CD3 immunoglobulin G (IgG)-based bispecific antibody (7370) with a high affinity for FLT3 and a long half-life, to target FLT3- ...