A Phase I/II Study of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Advanced Non-Hodgkin Lymphoma

NCT05205161 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: D8242C000012021-003410-39
• Study Type: interventional
• Target: 7
• Locations: 7 countries
• Sites: 10

Brief Summary

This study evaluates the safety, tolerability, PK, and preliminary efficacy of AZD0466 as monotherapy or in combination with other anticancer agents in patients with advanced NHL

Conditions

Non-Hodgkin Lymphoma

Keywords

Open-label,; Dose Escalation; Dose Expansion,; Multicentre Study; Anticancer; Pegylated poly-L-lysine dendrimer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events (AE)

  The safety and the tolerability of AZD0466 in patients with relapsed/ refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) was evaluated.

  Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month

• Number of Participants With Dose Limiting Toxicity (DLT)

  The DLT of AZD0466 in participants with R/R B-NHL was evaluated.

  Day 1 to end of Cycle 1 (28 days treatment cycle)

Secondary Outcomes (12)

• Part A: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320

  Cycle 1 Day 8, Cycle 2 Day 1

• Part A: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) of AZD4320

  Cycle 1 Day 8, Cycle 2 Day 1

• Part A: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) of AZD4320

  Cycle 1 Day 8 (Study Day 8), Cycle 2 Day 1 (Study Day 22)

• Part A: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) of AZD4320

  Cycle 1 Day 8, Cycle 2 Day 1

• Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After the Start of Infusion (AUC0-24) of AZD4320

  Cycle 1 Day 8, Cycle 2 Day 1

Study Arms (8)

Part A (Dose Escalation): Dose Level (DL)-1

EXPERIMENTAL

Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Drug: AZD0466

Part A (Dose Escalation): DL1

EXPERIMENTAL

Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Drug: AZD0466

Part A (Dose Escalation): DL2

EXPERIMENTAL

Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Drug: AZD0466

Part A (Dose Escalation): DL3

EXPERIMENTAL

Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Drug: AZD0466

Part A (Dose Escalation): DL4

EXPERIMENTAL

Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Drug: AZD0466

Part B (Dose Expansion): Cohort B1 (R/R MCL)

EXPERIMENTAL

Participants with advanced R/R MCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Drug: AZD0466

Part B (Dose Expansion): Cohort B2 (R/R FL or MZL)

EXPERIMENTAL

Participants with advanced R/R FL or MZL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Drug: AZD0466

Part B (Dose Expansion): Cohort B3 (R/R DLBCL)

EXPERIMENTAL

Participants with advanced R/R DLBCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Drug: AZD0466

Interventions

AZD0466 DRUG

All patients will receive treatment with the investigational product AZD0466 via intravenous infusion.

Part A (Dose Escalation): DL1; Part A (Dose Escalation): DL2; Part A (Dose Escalation): DL3; Part A (Dose Escalation): DL4; Part A (Dose Escalation): Dose Level (DL)-1; Part B (Dose Expansion): Cohort B1 (R/R MCL); Part B (Dose Expansion): Cohort B2 (R/R FL or MZL); Part B (Dose Expansion): Cohort B3 (R/R DLBCL)

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be aged ≥ 18 years at the time of signing the informed consent. In some countries, parental consent may be required in addition to an assent form for patients who are 18 years of age.

You may not qualify if:

• Patient has relapsed after or failed to respond to at least 2 but no more than 5 prior systemic treatment regimens (including investigational therapy) and for whom there is no available therapy expected to improve survival (eg, standard chemotherapy, autologous stem cell transplantation (SCT), chimeric antigen receptor T cell (CAR-T) cell therapy).
• Documented active disease requiring treatment that is relapsed or refractory defined as:
• Recurrence/relapse of disease after response to prior line(s) of therapy.
• Progressive disease (refractory) on/after completion of the treatment regimen preceding entry into the study.
• Must have at least one measurable, fluorodeoxyglucose positron emission tomography (FDG-PET) avid lesion (except for MZL), based on bi-dimensional assessment on PET and computed tomography (CT)/magnetic resonance imaging (MRI) scan. A measurable lesion is defined as:
• For nodal lesions: longest diameter \> 1.5 cm
• For extranodal lesions: longest diameter \> 1 cm
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2. Performance status must not have deteriorated by ≥ 2 levels within 2 weeks after providing informed consent.
• Adequate haematologic, hepatic, and renal function
• Adequate cardiac function as demonstrated by left ventricular ejection fraction \> 50% on screening cardiac multigated acquisition, magnetic resonance imaging, or echocardiogram.
• Women of childbearing potential and men should use protocol defined contraceptive measures.
• Willing and able to participate in all required study evaluations and procedures including receiving IV administration of study intervention and admission to the hospital, when required, for administration of study treatment and monitoring.
• All patients must be willing to undergo an incisional or excisional lymph node or tissue biopsy or to provide a lymph node or tissue biopsy from the most recent available archival tissue.
• Histologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1, as assessed by Investigator or local pathologist.
• Must have relapsed after or failed to respond to at least 2 prior lines of treatment, including one anti-CD20 monoclonal antibody (mAb) and a Bruton's tyrosine kinase inhibitor.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (10)

Research Site

Duarte, California, 91010, United States

Location

Research Site

Heidelberg, 3084, Australia

Location

Research Site

Lille, 59037, France

Location

Research Site

Milan, 20141, Italy

Location

Research Site

Porto, 4200-072, Portugal

Location

Research Site

Seoul, 06591, South Korea

Location

Research Site

Seoul, 110-744, South Korea

Location

Research Site

Palma de Mallorca, 07010, Spain

Location

Research Site

Pamplona, 31008, Spain

Location

Research Site

Salamanca, 37007, Spain

Location

Related Links

• D8242C00001\_CSP\_Redacted
• D8242C00001\_CSR Synopsis\_Redacted
• D8242C00001\_SAP\_Redacted

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

AZD0466

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

In this study, no participants were enrolled/screened in Module 1 Part B of this study, thus only results from Module 1 Part A will be presented in the report.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2022
• First Posted: January 25, 2022
• Study Start: July 5, 2022
• Primary Completion: August 17, 2023
• Study Completion: August 17, 2023
• Last Updated: January 7, 2025
• Results First Posted: January 7, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patientlevel data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

Locations

KR (2); AU (1); FR (1); IT (1); PT (1); US (1); ES (3)