Safety and Preliminary Efficacy Assessment of AZD7789 in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

• ClinicalTrials.gov Identifier: NCT05216835
• Recruitment Status: Active, not recruiting
• First Posted: February 1, 2022
• Last Update Posted: May 16, 2024
• Sponsor: AstraZeneca
• Collaborator: Parexel
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

The study is intended to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AZD7789 in patients with relapsed/refractory classical Hodgkin Lymphoma (r/r cHL).

Condition or disease	Intervention/treatment	Phase
Relapsed or Refractory Classical Hodgkin Lymphoma	Drug: AZD7789	Phase 1; Phase 2

Detailed Description:

This is a Phase I/II, open-label multi-center study will have AZD7789 administered via intravenous infusion on Cycle 1 Day 1 to adult/young adult patients with relapsed/refractory classical Hodgkin Lymphoma (r/r cHL). This study will have 2 parts: Phase 1 (Part A) Dose Escalation and Phase 2 (Part B) Dose Expansion.

Patients will be treated with study intervention for a maximum of 35 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent, or if other reasons to discontinue treatment occur.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 45 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Open-label, Multi-center Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD7789, an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma.
• Actual Study Start Date: March 18, 2022
• Estimated Primary Completion Date: February 23, 2026
• Estimated Study Completion Date: October 15, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort A: Dose Escalation; Patients with anti-PD-1/PD-L1 exposed r/r cHL will receive AZD7789.	Drug: AZD7789; Patients will receive AZD7789 (PD-1/TIM-3 bispecific monoclonal antibody) via intravenous infusion.
Experimental: Cohort B1: Dose Expansion; Patients with anti-PD-1/PD-L1 exposed r/r cHL will receive AZD7789 once the recommended phase 2 dose (RP2D) has been determined.	Drug: AZD7789; Patients will receive AZD7789 (PD-1/TIM-3 bispecific monoclonal antibody) via intravenous infusion.
Experimental: Cohort B2: Dose Expansion; Patients with anti-PD-1/PD-L1 naïve r/r cHL will receive AZD7789 once the RP2D has been determined.	Drug: AZD7789; Patients will receive AZD7789 (PD-1/TIM-3 bispecific monoclonal antibody) via intravenous infusion.

Outcome Measures

Primary Outcome Measures :

1. Part A (Dose Escalation): Number of incidence of adverse events (AEs) [ Time Frame: Approximately up to 2 years 90 days ]
   To assess safety and tolerability of AZD7789 in patients with r/r cHL.
2. Part A (Dose Escalation): Number of patients with dose-limiting toxicities (DLTs) [ Time Frame: From first dose until 28 days from the last patient first dose [within 28 days DLT period] ]
   To determine the maximum tolerated dose (MTD). To determine the incidence of DLT.
3. Part B (Dose Expansion): Cohort B1: Objective response rate (ORR) [ Time Frame: Up to 2 years of treatment ]
   To assess anti-tumor activity of AZD7789 in patients with r/r cHL. ORR defined as CR + PR as per modified Lugano criteria (Lugano 2014).
4. Part B (Dose Expansion): Cohort B2: Complete response rate (CRR) [ Time Frame: Up to 2 years of treatment ]
   To assess anti-tumor activity of AZD7789 in patients with r/r cHL. CRR is defined as CR as per modified Lugano criteria (Lugano 2014).
5. Part B (Dose Expansion): Number of incidence of adverse events (AEs) [ Time Frame: Approximately up to 2 years 90 days ]
   To assess safety and tolerability of AZD7789 in patients with r/r cHL.

Secondary Outcome Measures :

1. Part A (Dose Escalation): Complete Response Rate (CRR) [ Time Frame: Up to 2 years of treatment ]
   To assess anti-tumor activity of AZD7789 in patients with r/r cHL. CRR is defined as CR as per modified Lugano criteria (Lugano 2014).
2. Part A (Dose Escalation): Objective Response Rate (ORR) [ Time Frame: Up to 2 years of treatment ]
   To assess anti-tumor activity of AZD7789 in patients with r/r cHL. ORR defined as CR + PR as per modified Lugano criteria (Lugano 2014).
3. Part A (Dose Escalation): Duration of Response (DoR) [ Time Frame: Up to approximately 5 years ]
   To assess DoR of AZD7789 in patients with r/r cHL.
4. Part A (Dose Escalation): Duration of Complete Response (DoCR) [ Time Frame: Up to approximately 5 years ]
   To assess DoCR of AZD7789 in patients with r/r cHL
5. Part A (Dose Escalation): Progression-free Survival (PFS) [ Time Frame: Up to approximately 5 years ]
   To assess anti-tumor activity of AZD7789 in patients with r/r cHL.
6. Part A (Dose Escalation): Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]
   To assess anti-tumor activity of AZD7789 in patients with r/r cHL.
7. Part A (Dose Escalation): Number of patients with positive anti-drug antibodies against AZD7789 in serum [ Time Frame: Up to 2 years ]
   To assess the presence of anti-drug antibodies for AZD7789 in treated patients with r/r cHL.
8. Part A (Dose Escalation): Maximum observed concentration (Cmax) [ Time Frame: Up to 2 years ]
   To assess the Cmax of AZD7789 in patients with r/r cHL.
9. Part A (Dose Escalation): Area under the concentration-time curve (AUC) [ Time Frame: Up to 2 years ]
   To assess AUC of AZD7789 in patients with r/r cHL.
10. Part A (Dose Escalation): Terminal elimination half-life (t½) [ Time Frame: Up to 2 years ]
    To assess t½ of AZD7789 in patients with r/r cHL.
11. Part B (Dose Expansion): Duration of Response (DoR) [ Time Frame: Up to approximately 5 years ]
    To assess DoR of AZD7789 in patients with r/r cHL.
12. Part B (Dose Expansion): Duration of Complete Response (DoCR) [ Time Frame: Up to approximately 5 years ]
    To assess DoCR of AZD7789 in patients with r/r cHL
13. Part B (Dose Expansion): Progression-free Survival (PFS) [ Time Frame: Up to approximately 5 years ]
    To assess anti-tumor activity of AZD7789 in patients with r/r cHL.
14. Part B (Dose Expansion): Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]
    To assess anti-tumor activity of AZD7789 in patients with r/r cHL.
15. Part B (Dose Expansion): Number of patients with positive anti-drug antibodies against AZD7789 in serum [ Time Frame: Up to 2 years ]
    To assess the presence of anti-drug antibodies for AZD7789 in treated patients with r/r cHL.
16. Part B (Dose Expansion): Maximum observed concentration (Cmax) [ Time Frame: Up to 2 years ]
    To assess the Cmax of AZD7789 in patients with r/r cHL.
17. Part B (Dose Expansion): Area under the concentration-time curve (AUC) [ Time Frame: Up to 2 years ]
    To assess AUC of AZD7789 in patients with r/r cHL.
18. Part B (Dose Expansion): Terminal elimination half-life (t½) [ Time Frame: Up to 2 years ]
    To assess t½ of AZD7789 in patients with r/r cHL.
19. Part B (Dose Expansion): Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: Up to 2 years of treatment ]
    Proportion of participants reporting different levels of presence/magnitude/interference (as applicable) of diarrhea, rash, and fatigue over time based on PRO-CTCAE will be evaluated.
20. Part B (Dose Expansion): Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Peds-PRO-CTCAE) [ Time Frame: Up to 2 years of treatment ]
    Proportion of participants reporting different levels of presence/magnitude/interference (as applicable) of diarrhea, rash, and fatigue over time based on peds-PRO-CTCAE will be evaluated.
21. Part B (Dose Expansion): Patient Global Impression of Treatment Tolerability (PGI-TT) [ Time Frame: Up to 2 years of treatment ]
    Proportion of participants reporting different levels of overall side-effect bother over time based on the PGI-TT.
22. Part B (Dose Expansion): European Organization for Research and Treatment of Cancer (EORTC) Item List (IL)XX QL2 (2-item global health-related quality of life (HRQoL)) [ Time Frame: Up to 2 years of treatment ]
    Proportion of participants reporting different levels of quality of life/health over time based on the European Organization for Research and Treatment of Cancer Item List (EORTC) ILXX QL2 items will be evaluated.

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 101 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• ≥ 16 years of age at the time of obtaining informed consent
• Eastern Cooperative Oncology Group performance status of 0 or 1 at screening
• At least one PET-avid measurable lesion according to Modified Lugano Criteria after the last line of therapy.
• Confirmed histological diagnosis of active relapse/refractory cHL
• Failed at least 2 prior lines of systemic therapy.
• No previous treatment with anti-TIM-3.
• Adequate organ and bone marrow function
• Non-pregnant women and willingness of female patients to avoid pregnancy or male participants willing to avoid fathering children through highly effective methods of contraception
• Minimum body weight ≥ 40 kg for all participants.

Exclusion Criteria:

• Unresolved toxicities of ≥ Grade 2 from prior therapy
• Any prior ≥ Grade 3 imAE while receiving prior checkpoint inhibitor immunotherapy
• Patients with CNS involvement or leptomeningeal disease.
• History of organ transplantation (e.g., stem cell or solid organ transplant).
• Any venous or arterial thromboembolic event within ≤ 6 months prior to the first dose of study intervention.
• Active infection including TB, HIV, hepatitis A, chronic or active hepatitis B, chronic or active hepatitis C, active COVID-19 infection
• History of arrhythmia which is requires treatment, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
• Uncontrolled intercurrent illness.
• Active or prior documented pathologically confirmed autoimmune or inflammatory disorders.
• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
• Other invasive malignancy within 2 years prior to screening
• Congenital long QT syndrome or history of QT prolongation associated with other medications that cannot be changed or discontinued based on a cardiologist assessment
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study intervention
• Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.

Contacts and Locations

Locations

United States, California

Research Site

Duarte, California, United States, 91010

United States, Florida

Research Site

Miami, Florida, United States, 33136

United States, Minnesota

Research Site

Rochester, Minnesota, United States, 55905

United States, New York

Research Site

New York, New York, United States, 10065

United States, Texas

Research Site

Houston, Texas, United States, 77030

Canada, Ontario

Research Site

Toronto, Ontario, Canada, M5G 1X6

Canada, Quebec

Research Site

Montreal, Quebec, Canada, H3T 1E2

Denmark

Research Site

København Ø, Denmark, 2100

France

Research Site

Lille Cedex, France, 59037

Italy

Research Site

Bologna, Italy, 40138

Research Site

Napoli, Italy, 80131

Spain

Research Site

Valencia, Spain, 46010

United Kingdom

Research Site

Manchester, United Kingdom, M20 4BX

Research Site

Oxford, United Kingdom, 0X3 7LJ

Sponsors and Collaborators

AstraZeneca

Parexel

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05216835
• Other Study ID Numbers: D9571C00001; 2021-003569-36 ( EudraCT Number )
• First Posted: February 1, 2022
• Last Update Posted: May 16, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• 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 rerefer 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 patient-level 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.
• URL: https://vivli.org/

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

Keywords provided by AstraZeneca:

Pharmacokinetics; Classical Hodgkin Lymphoma (cHL); Dose Expansion; Dose escalation; r/r cHL; programmed cell death protein-1 (PD-1); Accelerated titration design (ATD); T cell immunoglobulin and mucin domain-containing protein-3(TIM-3); Modified toxicity probability interval-2 (mTPI-2); Bispecific antibody; Immunotherapy

Additional relevant MeSH terms:

Lymphoma; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases