IMGN632 + Venetoclax/Azacitidine for Acute Myeloid Leukemia

Not currently recruiting at 62 trial locations

Overseen By ImmunoGen Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ImmunoGen, Inc.

Must not be taking: IMGN632

Disqualifiers: CNS AML, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

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 IMGN632, used alone or with the drugs azacitidine (a chemotherapy drug) and/or venetoclax (a targeted therapy), for individuals with acute myeloid leukemia (AML). The focus is on those whose AML has returned or who have not yet been treated and have a specific protein called CD123 in their leukemia cells. This trial may suit someone diagnosed with CD123-positive AML who has not responded to standard treatments or is newly diagnosed and not eligible for standard intensive therapies.

As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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, you cannot have received any anticancer therapy within 14 days before starting the study, except for hydroxyurea, which is allowed before beginning the study treatment.

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

Research has shown that IMGN632, a treatment for acute myeloid leukemia (AML), is generally safe for patients. In studies where patients used IMGN632 alone, they tolerated it well. Some experienced mild to moderate side effects, but these were usually manageable. When combined with other drugs like azacitidine and venetoclax, IMGN632 maintained a good safety profile.

One study found that using IMGN632 with azacitidine and venetoclax helped many patients reach a point where no minimal residual disease (MRD) was detected, indicating effectiveness without serious harm. Another study also reported that this combination had manageable side effects and showed promise in treating leukemia.

Overall, while some side effects occurred, patients generally tolerated the treatment well, and the benefits seemed to outweigh the risks for many. This suggests that IMGN632 could be a safe option for those considering joining clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about IMGN632 for acute myeloid leukemia (AML) because it targets CD123, a protein commonly found on leukemia cells, offering a novel mechanism of action compared to current treatments like chemotherapy and stem cell transplants. Unlike traditional options, IMGN632 is an antibody-drug conjugate, which means it delivers chemotherapy directly to cancer cells, potentially minimizing damage to healthy cells. Additionally, when combined with venetoclax and azacitidine, IMGN632 might enhance the effectiveness of these drugs, providing a promising new approach for both newly diagnosed and relapsed/refractory AML patients.

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

Previous studies have shown that IMGN632, a treatment targeting the protein CD123, holds promise in fighting acute myeloid leukemia (AML). In this trial, some participants will receive IMGN632 alone, which has proven effective against leukemia. Others will receive a combination of IMGN632 with azacitidine and venetoclax. Past research has demonstrated that this combination leads to high rates of complete remission and rapid responses in difficult-to-treat cases. Azacitidine and venetoclax enhance each other's effects, and adding IMGN632 appears to further improve these benefits. This combination has shown potential for better outcomes in patients with relapsed or hard-to-treat AML. ^{2 3 5 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with CD123-positive Acute Myeloid Leukemia (AML) who have either relapsed or are treatment-naive can join this trial. They must be fit for experimental therapy, not have acute promyelocytic leukemia, and should not have had certain prior treatments. Participants need normal organ function and controlled previous cancers if any.

Inclusion Criteria

My AML is CD123-positive as confirmed by tests.

My heart pumps well, with an ejection fraction of 45% or higher.

I have had up to 2 previous cancer treatments.

Exclusion Criteria

I have had a liver condition called sinusoidal obstruction syndrome.

I do not have AML related to myeloproliferative neoplasm for the study's next phase.

I have had a severe allergic reaction to monoclonal antibodies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1b Dose Escalation Cohort to determine the recommended Phase 2 dose (RP2D) of IMGN632 in combination regimens

21-28 days per cycle

Dose Expansion

Phase 2 Dose Expansion Cohort to further characterize the safety profile and assess antileukemia activity

21-28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

approximately 20 months

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• IMGN632
• Venetoclax

Trial Overview The safety and effectiveness of IMGN632 alone or combined with azacitidine and/or venetoclax in treating AML are being tested. This study is open-label, meaning everyone knows which treatment they're getting, and it's happening at multiple centers.

How Is the Trial Designed?

Group I: Regimen D (Closed to Enrollment) Experimental Treatment 1 Intervention

IMGN632, administered intravenously on Day 1 of a 21 day cycle at 0.045 mg/kg, as a monotherapy for Fit and Unfit MRD+ patients.

Group II: Regimen C-Frontline&Relapsed/Refractory(Closed to Enrollment) Experimental Treatment 3 Interventions

IMGN632, administered intravenously on Day 7 of a 28 day cycle at 0.015 mg/kg or 0.045 mg/ kg, in combination with azacitidine, administered subcutaneously or intravenously daily at 35-75 mg/ m2 given for Days 1 to 7 of a 28 day cycle and venetoclax, administered orally daily at 100 mg on Day 1, 200mg on Day 2, and 400 mg on Day 3 up to Day 28 of a 28 day cycle. Alternate schedules with reduced venetoclax administration or reduced azacitidine dose or administration may be explored.

Group III: Regimen B (Closed to Enrollment) Experimental Treatment 2 Interventions

IMGN632, administered intravenously on Day 7 of a 21 day cycle at 0.015 mg/kg, 0.045 mg/kg, or 0.09 mg/kg, in combination with venetoclax, administered orally daily at 100 mg on Day 1, 200mg on Day 2, and 400 mg on the day 3 up to Day 21 of a 21 day cycle. Alternate schedules with reduced venetoclax administration may be explored.

Group IV: Regimen A (Closed to Enrollment) Experimental Treatment 2 Interventions

IMGN632, administered intravenously on Day 7 of a 28 day cycle at 0.015 mg/kg, 0.045 mg/kg, or 0.09 mg/kg, in combination with azacitidine, administered subcutaneously or intravenously daily at 75 mg/m2 on Days 1 to 7 of a 28 day cycle. Cycle 1 azacitidine dose in subsequent cohorts may be reduced.

Who Is Running the Clinical Trial?

ImmunoGen, Inc.

Lead Sponsor

Trials

33

Recruited

4,000+

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

In treatment-naïve patients with IDH1/2-mutant acute myeloid leukemia (AML), the combination of venetoclax and azacitidine resulted in a high composite complete remission rate of 79% and a median overall survival of 24.5 months, significantly outperforming the azacitidine-only group, which had an 11% remission rate and 6.2 months of survival.

The treatment was found to be safe, with no unexpected toxicities reported, and the favorable outcomes for patients with IDH1/2 mutations were consistent regardless of their cytogenetic risk, indicating a robust efficacy of this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations. Pollyea, DA., DiNardo, CD., Arellano, ML., et al.[2023]

A lower dosage of Venetoclax (100 mg) combined with Azacitidine showed favorable outcomes in newly diagnosed acute myeloid leukemia (AML) patients, with a median overall survival of 17 months and an overall response rate of 69.4% based on a study of 36 patients.

The study suggests that even with dose reductions of Venetoclax, the combination therapy remains effective, indicating a potential strategy to manage therapy-related toxicity while still achieving significant treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced duration and dosage of venetoclax is efficient in newly diagnosed patients with acute myeloid leukemia. Cui, J., Chen, X., Li, C., 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]

In a phase III study involving 127 treatment-naïve patients with acute myeloid leukemia and poor-risk cytogenetics, the combination of venetoclax and azacitidine significantly improved remission rates and overall survival in patients with TP53 wild-type (CRc of 70% and OS of 23.4 months) compared to azacitidine alone (CRc of 23% and OS of 11.3 months).

For patients with TP53 mutations, while venetoclax plus azacitidine improved remission rates (41% vs. 17% with azacitidine alone), it did not significantly enhance the duration of remission or overall survival, indicating that the treatment's efficacy may vary based on TP53 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in Patients with Poor-Risk Cytogenetics with or without TP53 Mutations Treated with Venetoclax and Azacitidine. Pollyea, DA., Pratz, KW., Wei, AH., et al.[2023]

In a Japanese subgroup of the phase 3 VIALE-A trial, venetoclax-azacitidine significantly improved overall survival rates compared to placebo-azacitidine, with 67% of patients alive at 12 months versus 46% in the placebo group.

The treatment also resulted in a high complete response (CR) and CR with incomplete hematologic recovery (CRi) rate of 67%, while maintaining a safety profile similar to the global study, indicating it is a viable first-line treatment for Japanese patients with acute myeloid leukemia ineligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Yamamoto, K., Shinagawa, A., DiNardo, CD., et al.[2023]

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]

The combination of venetoclax (Ven) and azacitidine (AZA) shows a high efficacy in treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), with an overall complete response rate of 57.9% across 19 studies involving 1615 patients.

This treatment is particularly effective for newly diagnosed AML patients, achieving a complete response rate of 67.5%, although it is less effective for those with relapsed or refractory AML, which had a response rate of only 30%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis. Du, Y., Li, C., Yan, J.[2023]

In a study of 35 patients with relapsed or refractory acute myeloid leukaemia (R/R AML) treated with venetoclax-azacitidine (VEN-AZA), the complete remission rate was significantly higher at 48.6% compared to 15% in a historical cohort treated with azacitidine (AZA).

Patients receiving VEN-AZA also showed a trend towards longer overall survival (12.8 months) compared to those treated with AZA (7.3 months), indicating that VEN-AZA may offer a more effective treatment option for R/R AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine-venetoclax versus azacitidine salvage treatment for primary induction failure or first relapsed acute myeloid leukaemia patients. Petit, C., Saillard, C., Mohty, B., et al.[2023]

In a study of 6 children with refractory or relapsed acute myeloid leukemia (AML), the combination of venetoclax, azacitidine, and cladribine (VAC regimen) resulted in significant treatment responses, with 4 achieving complete remission and 1 showing partial remission.

Despite severe side effects like grade IV neutropenia and thrombocytopenia, there were no treatment-related deaths or infections, indicating that the VAC regimen is both effective and safe for this vulnerable patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia]. DU, WW., Liu, SX., Wang, Y., et al.[2023]

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]

Citations

1. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00674-5/abstract

Pivekimab sunirine (IMGN632), a novel CD123-targeting ... Brandwein, JM ∙ Saini, L ∙ Geddes, MN ∙ et al. Outcomes of patients with relapsed or refractory acute myeloid leukemia: a population-based real-world study. Am ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118586511

Clinical Profile of IMGN632, a Novel CD123-Targeting ... ... Acute Myeloid Leukemia (AML) or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) ... RESULTS: 74 patients (67 AML, 7 BPDCN) have received IMGN632 ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2906/501756/Pivekimab-Sunirine-PVEK-IMGN632-a-CD123-Targeting

Pivekimab Sunirine (PVEK, IMGN632), a CD123-Targeting ... The PVEK+AZA+VEN triplet demonstrated anti-leukemia activity with robust CR rates and early MRD negative responses in a cohort enriched for adverse disease ...

4. news.abbvie.com news.abbvie.com/2021-12-12-ImmunoGen-Presents-Initial-Findings-From-the-Phase-1b-2-Study-of-IMGN632-in-Combination-With-Vidaza-R-and-Venclexta-R-in-Relapsed-Refractory-Acute-Myeloid-Leukemia-at-ASH

ImmunoGen Presents Initial Findings From the Phase 1b/2 ... IMGN632 is a CD123-targeting ADC in clinical development for hematological malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS6585

A phase 1b/2 study of pivekimab sunirine (PVEK, IMGN632 ... Treatment outcomes for newly diagnosed, untreated TP53-mutated acute myeloid leukemia: A systematic review and meta-analysis.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121023685

Safety and Efficacy from a Phase 1b/2 Study of IMGN632 in ... This Phase 1b/2 study was designed to determine the safety, tolerability, and preliminary anti-leukemic activity of IMGN632 combined with AZA and VEN in ...

7. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/734/426943/Clinical-Profile-of-IMGN632-a-Novel-CD123

Clinical Profile of IMGN632, a Novel CD123-Targeting ... RESULTS: 74 patients (67 AML, 7 BPDCN) have received IMGN632 across nine dose-escalation cohorts on two schedules, with dosing escalated from ...