AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia

• Sponsor: AstraZeneca (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06137118
• Collaborator: (none)
• Enrollment: 120
• Locations: 31
• Arms: 3
• Anticipated Duration (Months): 37.3
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 1/2, global multicentre, open-label, single-arm, dose escalation and dose optimisation study of AZD0486 to evaluate the safety, tolerability, and efficacy of AZD0486 monotherapy in participants with R/R B ALL who have received ≥ 2 prior lines of therapies. The study will consist of 3 parts. Part A monotherapy dose escalation. Part B dose optimisation. Part C Dose expansion at the recommended phase 2 dose (RP2D)

Condition or Disease	Intervention/Treatment	Phase
B-cell Acute Lymphoblastic Leukemia (B-ALL)	Drug: AZD0486	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: The trial will asses AZD0486 IV infusion in monotherapy. Part A will evaluate ascending dose levels of AZD0486 in participants 16-80 years with B-ALL. Part B will select the RP2D through a dose optimization process of safe-declared dose levels in participants with Ph(-) B-ALL aged 12-82 years. Part C will expand the RP2D dose level cohort to assess efficacy in a large number of subjects.The trial will asses AZD0486 IV infusion in monotherapy. Part A will evaluate ascending dose levels of AZD0486 in participants 16-80 years with B-ALL. Part B will select the RP2D through a dose optimization process of safe-declared dose levels in participants with Ph(-) B-ALL aged 12-82 years. Part C will expand the RP2D dose level cohort to assess efficacy in a large number of subjects.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study to Evaluate the Safety and Efficacy of AZD0486 in Adolescent and Adult Participants With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia
• Anticipated Study Start Date: Dec 26, 2023
• Anticipated Primary Completion Date: Jan 29, 2026
• Anticipated Study Completion Date: Feb 4, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: AZD0486 Dose Escalation Ascending dose level cohorts of AZD0486 in B-ALL participants aged 16-80 years.	Drug: AZD0486; Investigational Product administered via intervenous infusion.
Experimental: Part B: Dose Optimization Up to 2 cohorts will evaluated prior declared safe-doses and schedules in order to determine the recommended phase 2 dose (RP2D). Participants will receive AZD0486 IV infusions and randomized in a 1:1 ratio.	Drug: AZD0486; Investigational Product administered via intervenous infusion.
Experimental: Part C: Dose Expansion Part C will consist of 1 cohort of participants aged 12-80 years, treated with the optimal dose selected in Part B and receive IV AZD0486 monotherapy.	Drug: AZD0486; Investigational Product administered via intervenous infusion.

Outcome Measures

Primary Outcome Measures

1. Part A: Frequency of DLTs [28 days]

   DLTs are dose-limiting toxicities as defined in the study protocol

2. Parts A, B, C: Safety Evaluation of AZD0486 [From signing of informed consent through study completion, an average of 8 months]

   Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in physical examination and safety procedures.

3. Parts B & C: Overall Response Rate (ORR) [From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 24 months]

   The Primary analysis for ORR be conducted in RP2D-treated participants (in Part B and C).

Secondary Outcome Measures

1. Part A: Objective Response Rate (ORR) [From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 12 months]

   Overall response rate (ORR) in the evaluable participant set, defined as proportion of participants who achieve overall response (CR/CRi).

2. Parts A, B, C: Duration of response (DoR) [Up to 36 months]

   Date of first documented CR/CRi until the date of relapse or death

3. Parts A, B, C: CR rate at any time during the study [From first dose until end of study, up to 36 months]

   CR rate as defined as the percentage of participants achieving CR at any time by NCCN criteria

4. Parts A, B, C: Event-free survival (EFS) [From first dose until end of study, up to 36 months]

   Event-free survival is defined as the time from the date of the first dose until the date of a relapse after achieving a CR/ CRi, or death due to any cause.

5. Parts A, B, C: Overall survival (OS) [From first dose until end of study, up to 36 months]

   OS measured from first dose of study drug until death

6. Parts B & C: Subsequent alloSCT [From first dose until end of study, up to 24 months]

   Number of patients who after achieve CR/CR underwent an alloSCT

7. Parts B &C: CR MRD-negative rate [First dose until end of study, up to 24 months]

   Number of patients who achieve CR MRD-negative by NGS at any time on study

8. Parts A, B, & C: PK characterization of AZD0486 [From first dose until end of study, up to 36 months]

   Derived PK parameter: AUC

9. Parts A, B & C: PK Characterization of AZD0486 [From first dose until end of study, up to 36 months]

   Derived PK parameter: Cmax

10. Parts A, B, C: PK Characterization of AZD0486 [From first dose until end of study, up to 36 months]

    Derived PK Parameter: tmax

11. Parts A, B, C: PK Characterization of AZD0486 [From first dose until end of study, up to 36 months]

    Derived PK parameter: Ctrough

12. Parts A, B, C: PK Characterization of AZD0486 [Pre-defined intervals from day 1 to day 28]

    Derived PK Parameter: t1/2

13. Parts A, B, C: PK Characterization of AZD0486 [From first dose until end of study, up to 36 months]

    Derived PK Parameter: CL of AZD0486

14. Parts A, B, C: ADA characterization of AZD0486 [First dose up to 36 months]

    Number of participants who develop ADA during study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age: 16 years and older (Part A), 12 years and older (Parts B and C).

• Participants with CD19+ B-cell Acute Lymphoblastic Leukemia by local lab with:

1. Bone marrow infiltration with >/= 5% blasts

2. Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option.

3. Philadelphia positive participants are allowed in Part A if intolerant or refractory to TKIs.

• Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2 OR Lansky score more or equal to 50%.

The above is a summary, other inclusion criteria details may apply.

Exclusion Criteria:

• Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria).

• Isolated extramedullary disease relapse.

• Testicular leukemia

• History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy.

• History of other malignancy (with certain exceptions).

• Unresolved AEs >/= Grade 2, from prior therapies

• Prior therapy with TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 weeks or prior alloSCT within 12 weeks of start of therapy.

• GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment.

The above is a summary, other exclusion criteria details may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Duarte	California	United States	91010
2	Research Site	Los Angeles	California	United States	90048
3	Research Site	Tampa	Florida	United States	33612
4	Research Site	Houston	Texas	United States	77030
5	Research Site	Melbourne		Australia	3000
6	Research Site	Toronto	Ontario	Canada	M5G 2M9
7	Research Site	Montreal	Quebec	Canada	H3T1C5
8	Research Site	Montreal	Quebec	Canada	H4A 3J1
9	Research Site	Marseille		France	13009
10	Research Site	Paris		France	75019
11	Research Site	Pierre Bénite		France	69495
12	Research Site	Frankfurt A. Main		Germany	60590
13	Research Site	Freiburg		Germany	79106
14	Research Site	Halle		Germany	6120
15	Research Site	Hamburg		Germany	20246
16	Research Site	Koeln		Germany	50937
17	Research Site	Muenchen		Germany	D-81377
18	Research Site	Münster		Germany	48149
19	Research Site	Würzburg		Germany	97080
20	Research Site	Bologna		Italy	40138
21	Research Site	Monza		Italy	20900
22	Research Site	Roma		Italy	00165
23	Research Site	Seoul		Korea, Republic of	03080
24	Research Site	Seoul		Korea, Republic of	03722
25	Research Site	Seoul		Korea, Republic of	06351
26	Research Site	Seoul		Korea, Republic of	06591
27	Research Site	Barcelona		Spain	08035
28	Research Site	Madrid		Spain	28025
29	Research Site	Madrid		Spain	28046
30	Research Site	Valencia		Spain	46026
31	Research Site	Tainan City		Taiwan	70403

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT06137118
• Other Study ID Numbers: D7405C00001
• First Posted: Nov 18, 2023
• Last Update Posted: Nov 18, 2023
• Last Verified: Nov 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: B-cell acute lymphoblastic leukemia; Leukemia; B-lymphocytes; AZD0486
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid

Study Results

No Results Posted as of Nov 18, 2023