DSP107 + Azacitidine/Venetoclax for Leukemia

No longer recruiting at 1 trial location

Overseen By Yaffa Shwartz

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kahr Medical

Must be taking: Azacitidine, Venetoclax

Must not be taking: Immunostimulatory, CD47/SIRPα agents

Disqualifiers: Autoimmune disease, CNS leukemia, others

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

Compensation: Varies

Number of Visits: 214

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment option for individuals with certain types of leukemia, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), who have not succeeded with up to two previous treatments. The study consists of two parts: one evaluates the safety and effectiveness of an experimental drug called DSP107 when used with azacitidine, and the other adds venetoclax to the combination. For those with relapsed or hard-to-treat AML or MDS who have undergone a couple of unsuccessful treatments, this trial might be suitable. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have received certain treatments, like systemic immunostimulatory drugs, within 4 weeks before starting the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that DSP107, a new protein treatment, has been safe in early studies. These studies found no severe side effects that would prevent doctors from increasing the dose.

When combined with azacitidine, DSP107 appears well-tolerated. Azacitidine, commonly used to treat blood cancers, typically has known and manageable side effects.

For the combination of DSP107, azacitidine, and venetoclax, it is important to note that azacitidine and venetoclax are often used together to treat acute myeloid leukemia (AML). This combination can cause common side effects, primarily affecting blood counts. However, these side effects are expected in cancer treatments and are usually closely monitored.

Overall, previous patient data suggests that these treatment combinations could be manageable, but monitoring for side effects remains crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DSP107 in combination with azacitidine and venetoclax for leukemia because it brings a novel approach to treatment. Unlike standard therapies, DSP107 is an innovative immunotherapy that targets the CD47-SIRPα pathway, potentially enhancing the immune system's ability to attack cancer cells. By combining this with azacitidine and venetoclax, which are already effective in disrupting cancer cell growth and survival, this treatment may offer a more comprehensive attack on leukemia. This combination could lead to improved outcomes by harnessing the power of the immune system alongside existing chemotherapy agents.

What evidence suggests that this trial's treatments could be effective for leukemia?

Research has shown that DSP107, a special protein, can help the immune system fight cancer cells more effectively. It aids immune cells in destroying harmful cells, especially when combined with other treatments. In this trial, DSP107 will be administered with azacitidine, or with azacitidine plus venetoclax. Azacitidine, a common treatment for myelodysplastic syndrome (MDS), has been shown to help patients live longer by reducing abnormal blood cells. When combined with venetoclax, azacitidine has helped some patients achieve remission, meaning their disease symptoms disappear. Venetoclax is known for its success in treating blood cancers, making it a promising partner in combination therapies. Together, these treatments aim to improve outcomes in difficult-to-treat leukemia cases. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for patients with certain blood cancers like AML, MDS, or CMML who have tried and failed up to two treatments. They should have a white blood cell count under a specific limit, decent organ function, and be in fair to good physical condition (ECOG 0-2). It's not for those with severe liver disease, recent immunostimulatory treatment, active hepatitis B or C infection, lung issues, pregnancy/breastfeeding intentions during the study period.

Inclusion Criteria

My AML or MDS/CMML has not improved after up to 2 treatments.

I can take care of myself and am up and about more than 50% of my waking hours.

White Blood Cell count < 20 x 10^9/L

Exclusion Criteria

I have not received a live vaccine in the last 4 weeks.

I have not been treated with drugs targeting CD47/SIRPα or immune boosters.

I do not have any uncontrolled health conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Dose escalation study to explore the safety, efficacy, PK, and PD profile of DSP107 in combination with azacitidine (AZA).

28 days per cycle

Weekly visits for DSP107 infusion

Treatment Part B

Dose escalation study to explore the safety, efficacy, PK, and PD profile of DSP107 in combination with AZA and venetoclax (VEN).

28 days per cycle

Weekly visits for DSP107 infusion, daily dose escalation for venetoclax in Cycle 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• DSP107
• Venetoclax

Trial Overview

The trial tests DSP107 combined with azacitidine (AZA) in Part A and adds venetoclax (VEN) in Part B. Both parts aim to find safe doses while checking how well these combinations work against the cancer by monitoring their effects on the body and cancer cells.

How Is the Trial Designed?

Group I: DSP107 in combination with azacitidine or azacitidine plus venetoclax. Experimental Treatment 3 Interventions

DSP107 will be administered by intravenous infusion once weekly during each 28-day cycle to all patients in this study. Azacitidine (75 mg/m2/day) will be administered subcutaneously or intravenously for the first 7 days of every cycle. Patients enrolled in Part B only will also receive venetoclax. During Cycle 1, venetoclax will be dose escalated daily to the goal dose of 400 mg daily. Patients will receive 100 mg on Day 1, 200 mg on Day 2 and 400 mg on Day 3 and onwards.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Kahr Medical

Lead Sponsor

Trials

3

Recruited

160+

Published Research Related to This Trial

In patients with newly diagnosed unfit acute myeloid leukemia (AML), the combination of azacitidine and venetoclax is a standard first-line treatment.

However, patients with TP53-mutated AML and poor-risk cytogenetics do not benefit from adding venetoclax to azacitidine, suggesting that alternative treatment regimens should be considered for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TP53 or Not TP53: That Is the Question. Green, SD., Zeidner, JF.[2023]

In a phase 1/2 study involving six Japanese patients aged 60 and older with acute myeloid leukaemia, the combination of venetoclax and azacitidine demonstrated a high response rate, with 83% of patients achieving a response, including three complete remissions.

The treatment was generally well tolerated, with a median overall survival of 15.7 months, although some patients experienced serious adverse events, including grade 3 fungal pneumonia, which required treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. Taniguchi, S., Yamauchi, T., Choi, I., et al.[2021]

In a study of 13 patients with acute leukemia treated with venetoclax and azacitidine, 46% developed COVID-19, highlighting a significant risk associated with this treatment during the pandemic.

The study found that 33% of those who contracted COVID-19 died from the virus, indicating that COVID-19 can lead to severe outcomes in patients receiving AZA-VEN therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution. Drozd-Sokołowska, J., Mądry, K., Barankiewicz, J., et al.[2023]

Outpatient induction therapy using low-dose venetoclax combined with itraconazole and azacitidine is feasible and safe for newly diagnosed acute myeloid leukemia (ND-AML) patients, with 77.7% of participants completing the first treatment cycle as outpatients.

The treatment showed promising efficacy, with a composite complete response rate of 53.9% after the first cycle and 85.7% after the second cycle, indicating that this regimen could be a viable option for patients eligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose venetoclax plus itraconazole outpatient induction in newly diagnosed acute myeloid leukemia: A phase 2 study. De la Garza-Salazar, F., Colunga-Pedraza, PR., Gómez-Almaguer, D., et al.[2023]

Venetoclax combined with azacitidine or low-dose cytarabine (LDAC) is associated with significantly lower costs per patient achieving complete remission (CR) or complete remission with incomplete blood count recovery (CRi) compared to other treatments for newly diagnosed acute myeloid leukemia (AML) patients who cannot undergo intensive chemotherapy.

The estimated costs per patient achieving CR + CRi were $473,960 for venetoclax + azacitidine and $428,071 for venetoclax + LDAC, which are substantially lower than the costs for azacitidine ($1,197,438) and other therapies, indicating a more cost-effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Costs per patient achieving remission with venetoclax-based combinations in newly diagnosed patients with acute myeloid leukemia ineligible for intensive induction chemotherapy. Choi, M., Song, J., Bui, CN., et al.[2022]

In a study of 50 adults with acute myeloid leukemia (AML) in Mexico and Peru, venetoclax-based therapy showed a high complete response rate of 78.6% in newly diagnosed patients and 45.5% in those with relapsed/refractory disease, indicating its efficacy in treating AML.

The median overall survival was 9.6 months for newly diagnosed patients and 8 months for relapsed/refractory patients, suggesting that venetoclax is a viable treatment option even in real-world settings, despite common hematologic toxicities and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. Gómez-De León, A., Demichelis-Gómez, R., Pinedo-Rodríguez, A., et al.[2022]

In the HiDDAV study involving 42 newly diagnosed AML patients, higher doses of venetoclax (600 mg daily) were found to be tolerable but did not show significant clinical improvement compared to the standard 400 mg dose.

The study revealed that using minimal residual disease (MRD) status to guide the discontinuation of azacitidine did not lead to better outcomes in terms of duration of response or overall survival, suggesting that alternative strategies are needed to optimize treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. Gutman, JA., Winters, A., Kent, A., et al.[2023]

In a study of 57 elderly patients (average age 69.9 years) with acute myeloid leukemia, the combination of venetoclax and azacitidine (VEN + AZA) showed a high overall response rate of 87.5% and a complete remission (CR) rate of 68.8%, indicating strong efficacy in this population.

The treatment was associated with a median overall survival (OS) of 11.5 months, and achieving minimal residual disease (MRD) negativity (<0.1%) was more common with VEN + AZA compared to traditional chemotherapy, although older patients (≥75 years) and those with higher ECOG scores faced more challenges in achieving MRD negativity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients. Yu, H., Wang, C., Lei, Y., et al.[2023]

In a phase II study involving 60 older or unfit patients with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with cladribine and low-dose cytarabine alternating with venetoclax and 5-azacitidine resulted in a high composite complete response rate of 93%.

The treatment showed promising overall survival and disease-free survival rates, with only one death occurring within 4 weeks, indicating that this regimen is effective and has a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. Kadia, TM., Reville, PK., Wang, X., et al.[2023]

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UNMASKING CANCER CELL CAMOUFLAGE

DSP107 combination with Atezolizumab safe and well tolerated. • Two patients (10%) with deep, durable objective responses (~ 18 months).

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Part B is a dose escalation study to explore the safety, efficacy, PK and PD profile of DSP107 when administered in combination with AZA and venetoclax (VEN).