VIP943 for Blood Cancers

Recruiting at 4 trial locations

Overseen By Vincerx Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vincerx Pharma, Inc.

Disqualifiers: CNS metastases, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing VIP943, a new drug, to find the safest and most effective dose for patients with advanced blood cancers who have no other treatment options. The drug works by targeting a protein on cancer cells to help kill them or stop their growth.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What safety data exists for VIP943 in humans?

The combination of etoposide, ifosfamide, and cisplatin (VIP) has been used in various cancer treatments, showing that hematological toxicity (blood-related side effects) like neutropenia (low white blood cell count) is common but manageable. In some studies, the treatment was well-tolerated with mild to moderate side effects, except for one case of liver issues. ^{1 2 3 4 5}

What makes the drug VIP943 unique for treating blood cancers?

The drug VIP943 is unique because it is an immunoconjugate, which means it combines a monoclonal antibody targeting a specific antigen on cancer cells with a potent cytotoxic agent, potentially offering a more targeted approach compared to traditional chemotherapy. ^{1 3 5 6 7}

Research Team

Vincerx Study Director

Principal Investigator

Vincerx Pharma, Inc.

Eligibility Criteria

This trial is for people with advanced blood cancers like leukemia, who have a specific marker called CD123. They should be fairly active and able to care for themselves (ECOG 0-2) and must have tried all standard treatments or can't receive them. People with brain cancer spread or serious heart problems cannot join.

Inclusion Criteria

My cancer cells show CD123 presence.

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

My leukemia or myelodysplastic syndrome has not responded to standard treatments.

Exclusion Criteria

I do not have serious heart problems like recent heart attacks or severe chest pain.

My cancer has spread to my brain or its coverings.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VIP943 in sequential ascending doses as a monotherapy via intravenous administration

8-12 weeks

Weekly or twice weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• VIP943

Trial Overview The study is testing VIP943's safety and finding the highest dose patients can take without severe side effects in those with CD123+ hematologic malignancies. It starts with small doses that increase until they find the right balance between effectiveness and safety.

Participant Groups

Group I: Dose Escalation of VIP943 (QW) Experimental Treatment 1 Intervention

Subjects with AML, MDS, and B-ALL with CD123 expression will be administered VIP 943 in sequential ascending doses as a monotherapy via intravenous (IV) administration weekly (QW).

Group II: Dose Escalation of VIP943 (BIW) Experimental Treatment 1 Intervention

Subjects with AML, MDS, and B-ALL with CD123 expression will be administered VIP 943 in sequential ascending doses as a monotherapy via intravenous (IV) administration twice weekly (BIW).

Who Is Running the Clinical Trial?

Vincerx Pharma, Inc.

Lead Sponsor

Trials

4

Recruited

180+

Findings from Research

In a Phase II study involving 14 patients with advanced cervical carcinoma, the combination of VP-16 (etoposide), ifosfamide, and cisplatin (VIP) resulted in complete responses in 8 patients, with response durations lasting between 7 to over 24 months.

The VIP chemotherapy regimen was well-tolerated overall, with manageable hematologic toxicity being the primary side effect, indicating its potential as an effective treatment option for advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide (VP-16), ifosfamide/mesna, and cisplatin chemotherapy for advanced and recurrent carcinoma of the cervix. Kredentser, DC.[2019]

In a study of 10 patients with reactivated stage D prostatic cancer, the combination therapy of vincristine, ifosfamide, and peplomycin (VIP therapy) provided significant relief from bone pain in 50% of patients and improved urinary symptoms in 33%.

Despite some symptomatic relief, the overall objective response rate for treating primary and metastatic lesions was low, ranging from 10% to 20% depending on the evaluation criteria, with mild to moderate toxicity reported, except for one case of hepatic insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination chemotherapy of vincristine, ifosfamide and peplomycin in patients with reactivated prostatic cancer]. Kazama, T., Katayama, T., Umeda, K., et al.[2015]

In a study of 16 patients with metastatic germ cell tumors, 81% achieved a complete response to VIP therapy, which includes etoposide, ifosfamide, and cisplatin, indicating its effectiveness as a first-line chemotherapy.

The treatment was well tolerated despite causing significant myelosuppression (Grade 3 or higher), with no treatment-related deaths, suggesting that VIP therapy is a safe option for patients with good and intermediate prognostic groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment results of VIP (etoposide, ifosfamide and cisplatin) chemotherapy as a first-line therapy in metastatic germ cell tumors]. Yoshida, T., Yonese, J., Kitsukawa, S., et al.[2019]

In a study involving 10 acute leukemia patients, the new cytostatic agent VP 16-213 demonstrated effectiveness, achieving one complete remission and two partial remissions, indicating its potential as a treatment option for various forms of acute leukemia.

VP 16-213 has a relatively mild toxic effect and a unique mechanism of action, suggesting it could be safely integrated into combination chemotherapy regimens and warrants further clinical trials, especially for patients with refractory acute leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Initial results with a epipodophyllotoxin derivative VP 16-213 in the treatment of acute leukemia]. Cavalli, F., Ryssel, HJ., Batz, K., et al.[2013]

In a study of 24 patients with advanced or relapsed soft tissue sarcoma treated with the VIP regimen (etoposide, ifosfamide, and cisplatin), the overall response rate was 37.5%, indicating that VIP may be an effective second-line treatment option.

Patients who responded to previous chemotherapy showed significantly better overall survival (11.0 months) compared to nonresponders (8.8 months), highlighting the importance of prior treatment response in predicting outcomes with VIP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VIP (etoposide, ifosfamide, and cisplatin) in patients with previously treated soft tissue sarcoma. Moon, JY., Baek, SW., Ryu, H., et al.[2021]

In a study involving 38 adult patients with relapsed or refractory acute myeloid leukemia, VP-16-213 demonstrated an overall response rate of 18%, with 5% achieving complete remission and 13% partial remission.

The treatment was associated with mild toxicity and rare instances of aplasia, showing that it is a relatively safe option for patients across all myeloid subtypes, including those who had never achieved remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of VP 16-213 in adults with refractory acute myeloid leukemia. An Eastern Cooperative Oncology Group study. Bennett, JM., Lymann, GH., Cassileth, PA., et al.[2019]

AVE9633, an immunoconjugate targeting CD33 in acute myeloid leukemia (AML), shows that P-glycoprotein (P-gp) activity can reduce its cytotoxic effects, but this is not the main cause of resistance in AML patients, as 40% of samples were resistant regardless of P-gp levels.

The study suggests that combining AVE9633 with other treatments may be beneficial for AML patients resistant to standard therapies, as resistance mechanisms may involve factors beyond P-gp, such as alterations in microtubules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P-gp activity is a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines, but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients. Tang, R., Cohen, S., Perrot, JY., et al.[2021]

References

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

Etoposide (VP-16), ifosfamide/mesna, and cisplatin chemotherapy for advanced and recurrent carcinoma of the cervix. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

[Combination chemotherapy of vincristine, ifosfamide and peplomycin in patients with reactivated prostatic cancer]. [2015]

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

[Treatment results of VIP (etoposide, ifosfamide and cisplatin) chemotherapy as a first-line therapy in metastatic germ cell tumors]. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

[Initial results with a epipodophyllotoxin derivative VP 16-213 in the treatment of acute leukemia]. [2013]

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

VIP (etoposide, ifosfamide, and cisplatin) in patients with previously treated soft tissue sarcoma. [2021]

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

A phase II trial of VP 16-213 in adults with refractory acute myeloid leukemia. An Eastern Cooperative Oncology Group study. [2019]

7. England pubmed.ncbi.nlm.nih.gov

P-gp activity is a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines, but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients. [2021]