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

Relapsed or Refractory Classical Hodgkin Lymphoma Clinical Trial

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05216835
• Other study ID #: D9571C00001
• Secondary ID: 2021-003569-36
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 18, 2022
• Est. completion date: October 15, 2027

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 45
• Est. completion date: October 15, 2027
• Est. primary completion date: February 23, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 101 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma
• Relapsed or Refractory Classical Hodgkin Lymphoma

Intervention

Drug:
• AZD7789
Patients will receive AZD7789 (PD-1/TIM-3 bispecific monoclonal antibody) via intravenous infusion.

Locations

Country	Name	City	State
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Denmark	Research Site	København Ø
France	Research Site	Lille Cedex
Italy	Research Site	Bologna
Italy	Research Site	Napoli
Spain	Research Site	Valencia
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Oxford
United States	Research Site	Duarte	California
United States	Research Site	Houston	Texas
United States	Research Site	Miami	Florida
United States	Research Site	New York	New York
United States	Research Site	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A (Dose Escalation): Number of incidence of adverse events (AEs)	To assess safety and tolerability of AZD7789 in patients with r/r cHL.	Approximately up to 2 years 90 days
Primary	Part A (Dose Escalation): Number of patients with dose-limiting toxicities (DLTs)	To determine the maximum tolerated dose (MTD). To determine the incidence of DLT.	From first dose until 28 days from the last patient first dose [within 28 days DLT period]
Primary	Part B (Dose Expansion): Cohort B1: Objective response rate (ORR)	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).	Up to 2 years of treatment
Primary	Part B (Dose Expansion): Cohort B2: Complete response rate (CRR)	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).	Up to 2 years of treatment
Primary	Part B (Dose Expansion): Number of incidence of adverse events (AEs)	To assess safety and tolerability of AZD7789 in patients with r/r cHL.	Approximately up to 2 years 90 days
Secondary	Part A (Dose Escalation): Complete Response Rate (CRR)	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).	Up to 2 years of treatment
Secondary	Part A (Dose Escalation): Objective Response Rate (ORR)	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).	Up to 2 years of treatment
Secondary	Part A (Dose Escalation): Duration of Response (DoR)	To assess DoR of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Secondary	Part A (Dose Escalation): Duration of Complete Response (DoCR)	To assess DoCR of AZD7789 in patients with r/r cHL	Up to approximately 5 years
Secondary	Part A (Dose Escalation): Progression-free Survival (PFS)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Secondary	Part A (Dose Escalation): Overall Survival (OS)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Secondary	Part A (Dose Escalation): Number of patients with positive anti-drug antibodies against AZD7789 in serum	To assess the presence of anti-drug antibodies for AZD7789 in treated patients with r/r cHL.	Up to 2 years
Secondary	Part A (Dose Escalation): Maximum observed concentration (Cmax)	To assess the Cmax of AZD7789 in patients with r/r cHL.	Up to 2 years
Secondary	Part A (Dose Escalation): Area under the concentration-time curve (AUC)	To assess AUC of AZD7789 in patients with r/r cHL.	Up to 2 years
Secondary	Part A (Dose Escalation): Terminal elimination half-life (t½)	To assess t½ of AZD7789 in patients with r/r cHL.	Up to 2 years
Secondary	Part B (Dose Expansion): Duration of Response (DoR)	To assess DoR of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Secondary	Part B (Dose Expansion): Duration of Complete Response (DoCR)	To assess DoCR of AZD7789 in patients with r/r cHL	Up to approximately 5 years
Secondary	Part B (Dose Expansion): Progression-free Survival (PFS)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Secondary	Part B (Dose Expansion): Overall Survival (OS)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Secondary	Part B (Dose Expansion): Number of patients with positive anti-drug antibodies against AZD7789 in serum	To assess the presence of anti-drug antibodies for AZD7789 in treated patients with r/r cHL.	Up to 2 years
Secondary	Part B (Dose Expansion): Maximum observed concentration (Cmax)	To assess the Cmax of AZD7789 in patients with r/r cHL.	Up to 2 years
Secondary	Part B (Dose Expansion): Area under the concentration-time curve (AUC)	To assess AUC of AZD7789 in patients with r/r cHL.	Up to 2 years
Secondary	Part B (Dose Expansion): Terminal elimination half-life (t½)	To assess t½ of AZD7789 in patients with r/r cHL.	Up to 2 years
Secondary	Part B (Dose Expansion): Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	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.	Up to 2 years of treatment
Secondary	Part B (Dose Expansion): Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Peds-PRO-CTCAE)	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.	Up to 2 years of treatment
Secondary	Part B (Dose Expansion): Patient Global Impression of Treatment Tolerability (PGI-TT)	Proportion of participants reporting different levels of overall side-effect bother over time based on the PGI-TT.	Up to 2 years of treatment
Secondary	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))	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.	Up to 2 years of treatment