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

AstraZeneca

Status and phase: Active, not recruiting; Phase 1

Conditions: Relapsed or Refractory Classical Hodgkin Lymphoma

Treatments: Drug: Sabestomig (AZD7789)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05216835

D9571C00001

2021-003569-36 (EudraCT Number)

Details and patient eligibility

About

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

Full description

This is a Phase I/II, open-label multi-center study will have sabestomig 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.

The trial was intended to be Phase I/II trial (but the trial never moved forward to Phase 2). Hence, the study Phase was updated to Phase I.

Enrollment: 45 patients

Sex: All

Ages: 16 to 101 years old

Volunteers: No Healthy Volunteers

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 positron emission tomography (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 central nervous system (CNS) involvement or leptomeningeal disease.
• History of allogeneic stem cell transplant or organ transplantation.
• Any venous or arterial thromboembolic event within ≤ 6 months prior to the first dose of study intervention.
• Active infection including Tuberculosis (TB), human immunodeficiency virus (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 uncontrol led 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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45 participants in 3 patient groups

Cohort A: Dose Escalation

Experimental group

Description:

Patients with anti-PD-1/PD-L1 exposed r/r cHL will receive sabestomig to determine the recommended phase 2 dose (RP2D).

Treatment:

Drug: Sabestomig (AZD7789)

Cohort B1: Dose Expansion

Experimental group

Description:

Patients with anti-PD-1/PD-L1 exposed r/r cHL will receive sabestomig once the RP2D has been determined.

Treatment:

Drug: Sabestomig (AZD7789)

Cohort B2: Dose Expansion

Experimental group

Description:

Patients with anti-PD-1/PD-L1 naïve r/r cHL will receive sabestomig once the RP2D has been determined.

Treatment:

Drug: Sabestomig (AZD7789)