First-in-human Study of SAR443579 Infusion in Male and Female Participants of at Least 12 Years of Age With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL) or High Risk-myelodysplasia (HR-MDS)

• ClinicalTrials.gov Identifier: NCT05086315
• Recruitment Status: Recruiting
• First Posted: October 20, 2021
• Last Update Posted: January 6, 2023
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

This is an open-label, multicenter, Phase 1/Phase 2, dose escalation and dose expansion study to evaluate the safety, pharmacokinetics, pharmacodynamics and anti-leukemic activity of SAR443579 in various hematological malignancies.

Condition or disease	Intervention/treatment	Phase
Acute Lymphocytic Leukaemia; Acute Myeloid Leukaemia Refractory; Myelodysplastic Syndrome	Drug: SAR443579	Phase 1; Phase 2

Detailed Description:

2.5 years.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 82 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, First-in-human, Dose-escalation/Expansion Study of SAR443579 Administered as Single Agent by Intravenous Infusion in Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL) or High Risk-myelodysplasia (HR-MDS)
• Actual Study Start Date: December 8, 2021
• Estimated Primary Completion Date: August 26, 2025
• Estimated Study Completion Date: June 12, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: SAR443579; Dose Escalation: SAR443579 administered intravenously at escalating dose levels. Dose Expansion: SAR443579 administered intravenously at the recommended dose and schedule determined from the dose escalation.	Drug: SAR443579; Powder for solution for infusion; by IV infusion

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose-limiting toxicity (DLT) (Escalation Part) [ Time Frame: Day 1 to Day 28 ]
2. Proportion of participants who have a CR (Complete Remission) + CRi (Complete Remission with Incomplete Hematological Recovery) (Expansion Part) [ Time Frame: Up to 6 months ]

Secondary Outcome Measures :

1. Recommended Phase 2 dose (RP2D) [ Time Frame: Up to 12 months ]
2. Number of participants with treatment-emergent adverse events (TEAEs) (Escalation and Expansion Parts) [ Time Frame: Up to 30 months ]
3. Cmax: Maximum observed concentration [ Time Frame: Day 1 to end of trial (maximum up to 30 months) ]
4. AUC0-T: Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T) [ Time Frame: Day 1 to end of trial (maximum up to 30 months) ]
5. Incidence of anti-drug antibody (ADA) (Escalation and Expansion Parts) [ Time Frame: Up to 30 months ]
6. Anti-leukemic activity as define by International Working Group (IWG) for AML (modified) and MDS, or NCCN for B-ALL (Escalation Part) [ Time Frame: Up to 6 months ]
7. Proportion of participants with CR + CRh (complete remission with partial hematological recovery) (Expansion Part) [ Time Frame: Up to 6 months ]
8. Rate of CR + CRh + CRi + MLFS (morphological leukemia-free state) (Expansion Part) [ Time Frame: Up to 6 months ]
9. Time interval from first documented evidence of CR until progressive disease (PD) as per modified IWG or death due to any cause, whichever comes first (Expansion Part) [ Time Frame: Up to 30 months ]
10. Time interval from date of first SAR443579 administration to induction failure, relapse or death due to any cause, whichever comes first (Expansion Part) [ Time Frame: Up to 30 months ]
11. Proportion of survivors from the first SAR443579 administration to death from any cause (Expansion Part) [ Time Frame: Up to 12 months ]
12. Rate of HSCT through SAR443579 treatment but before subsequent therapy (Expansion Part) [ Time Frame: Up to 30 months ]
13. Time from first SAR443579 administration to discontinuation for any reason excluding remission, ie, disease progression, treatment toxicity, patient preference or death (Expansion Part) [ Time Frame: Up to 30 months ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

- Participant must be ≥12 years old at the time the trial participant or legal guardian signs the informed consent form.

For participants of the Escalation Part only:

- Confirmed diagnosis of primary or secondary AML [any subtype except acute promyelocytic leukemia (APL)] according to World Health Organization (WHO) classification. Patients with AML must meet one of the following criteria, a), b) or c) and are limited to those with no available (or are ineligible) therapy with known clinical benefit.

a) Primary Induction Failure (PIF) AML, defined as disease refractory to one of the following, i or ii.

i) An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens.

Examples include but are not limited to:

• One cycle of high dose cytarabine (HiDAC) containing regimen
• One cycle of liposomal cytarabine and daunorubicin

• Two cycles of standard dose cytarabine containing regimen ii) For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens, 1 or 2:

  1. 4 cycles of hypomethylating agents (HMA) or

  2. 2 cycles HMA + venetoclax b) Early relapse (ER) AML, defined as AML in relapse with CR duration < 6 months from most recent treatment c) Leukemia in first or higher relapse

     • Confirmed diagnosis of cluster of differentiation 123 (CD123) + HR-MDS, with a Revised International Prognostic Scoring System (IPSS-R) risk category of intermediate or higher and are limited to those with no available (or are ineligible) therapy with known clinical benefit.
• Not eligible for induction therapy and having completed ≥2 cycles of any of the following: hypomethylating agent (eg, 5 azacitidine or decitabine) and/or venetoclax, chemotherapy, or targeted agents.

• Not eligible for autologous stem cell transplant (ASCT) and having completed ≥1 course of induction therapy.

  • Confirmed diagnosis of CD123 + B-ALL without extramedullary lesions that have no available (or are ineligible) therapy with known clinical benefit.

For Participants in the Expansion Part Only:

• For participants in Cohort A: Participants meeting inclusion criteria for AML patients that have been primary refractory (PIF) to prior induction treatment or who have had ER occurring 6 months or less after an initial remission on prior induction treatment.
• For participants in Cohort B: Participants meeting inclusion criteria for AML patients that have had late relapse (LR), occurring more than 6 months after an initial remission on prior induction treatment.
• Body weight >40 kg. -- Body weight >40 kg. - - -

Exclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status >2 (≥18 years-old). Karnovsky Scale (16-17 years-old) <50% or Lansky Scale (<16 years-old) <50%.
• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that requires or required treatment with systemic immunosuppressive treatments, which may suggest a risk for immune-related adverse events. The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement or psoriasis that does not require systemic treatment.
• History of an invasive malignancy that requires active therapy (adjuvant hormonal therapy is allowed) other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
• Evidence of active central nervous system leukemia at the time of enrollment as evidenced by cytology or pathology.
• Known acquired immunodeficiency syndrome (AIDS-related illnesses) or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Prior treatment with an anti-CD123-directed agent.
• Prior HSCT with relapse beyond 3 months or prior CAR-T therapy in B-ALL with relapse beyond 2 months may be included only if off immunosuppression for a minimum of 4 weeks and no evidence of GVHD.
• Receiving at the time of first investigational medicinal product (IMP) administration corticosteroid as a concomitant medication with corticosteroid dose >10 mg/day of oral prednisone or the equivalent,
• AML or HR-MDS participants with prior treatment with cellular therapy, eg, chimeric antigen receptor T cell (CAR-T) or chimeric antigen receptor NK cell (CAR-NK). Prior CAR-T therapy is allowed for participants with B-ALL.
• Concurrent treatment with other investigational drugs.
• Radiotherapy, even if palliative in intent, may not be given during the study.
• Prophylactic use of hematopoietic growth factors (eg, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin) during the DLT observation period in the Dose Escalation Part only. - Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
• Pregnant and breast-feeding women.
• History of solid organ transplant, including corneal transplant.
• Average QTc (using the Fridericia correction calculation) >470 millisecond (msec) at screening.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Contacts and Locations

Contacts

Contact: Trial Transparency email recommended (Toll free for US & Canada); 800-633-1610 ext option 6; Contact-US@sanofi.com

Locations

United States, California

City of Hope-Site Number:8400002; Recruiting

Duarte, California, United States, 91010

United States, Georgia

Emory University-Site Number:8400006; Recruiting

Atlanta, Georgia, United States, 30322

United States, New York

Weill Cornell Medical College-Site Number:8400003; Recruiting

New York, New York, United States, 10021

United States, Texas

MD Anderson Cancer Center-Site Number:8400001; Recruiting

Houston, Texas, United States, 77230-1439

Australia, Victoria

Investigational Site Number :0360002; Recruiting

Melbourne, Victoria, Australia, 3000

Investigational Site Number :0360001; Recruiting

Melbourne, Victoria, Australia, 3004

France

Investigational Site Number :2500002; Recruiting

Marseille, France, 13009

Investigational Site Number :2500001; Recruiting

Paris, France, 75010

Investigational Site Number :2500003; Recruiting

Villejuif, France, 94800

Netherlands

Investigational Site Number :5280002; Recruiting

Amsterdam, Netherlands, 1081 HV

Investigational Site Number :5280003; Recruiting

Groningen, Netherlands, 9713 GZ

Investigational Site Number :5280005; Recruiting

Nijmegen, Netherlands, 6525GA

Investigational Site Number :5280001; Recruiting

Rotterdam, Netherlands, 3015 CE

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT05086315
• Other Study ID Numbers: TCD17197; U1111-1266-7399 ( Registry Identifier: ICTRP ); 2021-004287-98 ( EudraCT Number )
• First Posted: October 20, 2021
• Last Update Posted: January 6, 2023
• Last Verified: January 5, 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases