Clinical trial NCT05216835: Safety and Preliminary Efficacy Assessment of AZD7789 in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Relapsed or Refractory Classical Hodgkin Lymphoma
Keywords: 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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2022-02-01
Enrollment: 45
Sex: ALL
Minimum age (years): 16
Maximum age (years): 101
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.

Eligibility 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 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.

Primary outcomes:
measure: Part A (Dose Escalation): Number of Participants With Adverse Events (AEs)
timeFrame: From start of treatment [Cycle 1 Day 1 (C1D1) (each cycle was 28 days)] up to 90 days post last dose (approximately 2 years 5 months)
measure: Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: From first dose (C1D1) until 28 days for each participant [within 28 days DLT period]
measure: Part B (Dose Expansion): Cohort B1: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Cohort B2: Complete Response Rate (CRR)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Number of Participants With AEs
timeFrame: Up to approximately 2 years 90 days
Secondary outcomes:
measure: Part A (Dose Escalation): Complete Response Rate (CRR)
timeFrame: From start of treatment [C1D1 (each cycle was 28 days)] until first documented disease progression, or last evaluable assessment in the absence of progression (up to 2 years 5 months)
measure: Part A (Dose Escalation): Objective Response Rate (ORR)
timeFrame: From start of treatment [C1D1 (each cycle was 28 days)] until progression, or last evaluable assessment in the absence of progression (up to 2 years 5 months)
measure: Part A (Dose Escalation): Duration of Response (DoR)
timeFrame: From first documented response until date of first documented disease progression or death from any cause, or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
measure: Part A (Dose Escalation): Duration of Complete Response (DoCR)
timeFrame: From first documented complete response until date of first documented disease progression or death from any cause, or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
measure: Part A (Dose Escalation): Progression-free Survival (PFS)
timeFrame: From start of treatment [C1D1 (each cycle was 28 days)] until date of first documented disease progression or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
measure: Part A (Dose Escalation): Overall Survival (OS)
timeFrame: From start of treatment [C1D1 (each cycle was 28 days)] until date of death due to any cause or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
measure: Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum
timeFrame: On C1D1, C2D1, and until end of study [up to 2 years 5 months (each cycle was 28 days)]
measure: Part A (Dose Escalation): Maximum Observed Concentration (Cmax)
timeFrame: From C1D1 [before start of infusion (SOI) and at end of infusion (EOI)] to end of study [up to 2 years 5 months (each cycle was 28 days)]
measure: Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC)
timeFrame: From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)]
measure: Part A (Dose Escalation): Clearance (CL)
timeFrame: From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)]
measure: Part A (Dose Escalation): Terminal Elimination Half-life (t½λz)
timeFrame: From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)]
measure: Part B (Dose Expansion): Duration of Response (DoR)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Duration of Complete Response (DoCR)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Progression-free Survival (PFS)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Overall Survival (OS)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Number of Participants With Positive ADA Against Sabestomig in Serum
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Maximum Observed Concentration (Cmax)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Area Under the Concentration-time Curve (AUC)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Terminal Elimination Half-life (t½λz)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Pediatric Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (Peds-PRO-CTCAE)
timeFrame: Up to approximately 2 years 90 days
measure: Part B (Dose Expansion): Patient Global Impression of Treatment Tolerability (PGI-TT)
timeFrame: Up to approximately 2 years 90 days
measure: 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)]
timeFrame: Up to approximately 2 years 90 days
Other outcomes:
measure: Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: From start of treatment [C1D1 (each cycle was 28 days)] up to 90 days post last dose (approximately 2 years 5 months)
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Miami
country: United States
facility: Research Site
state: Florida
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: New York
country: United States
facility: Research Site
state: New York
city: Houston
country: United States
facility: Research Site
state: Texas
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: København Ø
country: Denmark
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
Study officials:
References: